Isomer of per- and polyfluoroalkyl substances and red blood cell indices in adults: The Isomers of C8 Health Project in China.

This study aimed to explore the isomer-specific, sex-specific, and joint associations of PFAS and red blood cell indices. We used data of 1,238 adults from the Isomers of C8 Health Project in China. Associations of PFAS isomers and red blood cell indices were explored using multiple linear regression models, Bayesian Kernel Machine Regression models and subgroup analysis across sex. We found that serum concentration of linear (n-) and branched (Br-) isomers of perfluorooctane sulfonate (PFOS) and perfluorohexanesulfonic acid (PFHxS) were significantly associated with red blood cell indices in single-pollutant models, with stronger associations observed for n-PFHxS than Br-PFHxS, in women than in men. For instance, the estimated percentage change in hemoglobin concentration for n-PFHxS (3.65%; 95% CI: 2.95%, 4.34%) was larger than that for Br-PFHxS (0.96%; 95% CI: 0.52%, 1.40%). The estimated percentage change in red blood cell count for n-PFHxS in women (2.55%; 95% CI: 1.81%, 3.28%) was significantly higher than that in men (0.12%; 95% CI: -1.04%, 1.29%) (Pinter < 0.001). Similarly, sex-specific positive association of PFAS mixture and outcomes was observed. Therefore, the structure, susceptive population, and joint effect of PFAS isomers should be taken into consideration when evaluating the health risk of chemicals.

From follicle to blastocyst: microRNA-34c from follicular fluid-derived extracellular vesicles modulates blastocyst quality.

BACKGROUND: Within the follicular fluid, extracellular vesicles (EVs) guide oocyte growth through their cargo microRNAs (miRNAs). Here, we investigated the role of EVs and their cargo miRNAs by linking the miRNAs found in EVs, derived from the fluid of an individual follicle, to the ability of its oocyte to become a blastocyst (competent) or not (non-competent). METHODS: Bovine antral follicles were dissected, categorized as small (2-4 mm) or large (5-8 mm) and the corresponding oocytes were subjected to individual maturation, fertilization and embryo culture to the blastocyst stage. Follicular fluid was pooled in 4 groups (4 replicates) based on follicle size and competence of the corresponding oocyte to produce a blastocyst. Follicular fluid-derived EVs were isolated, characterized, and subjected to miRNA-sequencing (Illumina Miseq) to assess differential expression (DE) in the 4 groups. Functional validation of the effect of miR-34c on embryo development was performed by supplementation of mimics and inhibitors during in vitro maturation (IVM). RESULTS: We identified 16 DE miRNAs linked to oocyte competence when follicular size was not considered. Within the large and small follicles, 46 DE miRNAs were driving blastocyst formation in each group. Comparison of EVs from competent small and large follicles revealed 90 DE miRNAs. Cell regulation, cell differentiation, cell cycle, and metabolic process regulation were the most enriched pathways targeted by the DE miRNAs from competent oocytes. We identified bta-miR-34c as the most abundant in follicular fluid containing competent oocytes. Supplementation of miR-34c mimic and inhibitor during IVM did not affect embryo development. However, blastocyst quality, as evidenced by higher cell numbers, was significantly improved following oocyte IVM in the presence of miR-34c mimics, while miR-34c inhibitors resulted in the opposite effect. CONCLUSION: This study demonstrates the regulatory effect of miRNAs from follicular fluid-derived EVs on oocyte competence acquisition, providing a further basis for understanding the significance of miRNAs in oocyte maturation and embryonic development. Up-regulation of miR-34c in EVs from follicular fluid containing competent oocytes and the positive impact of miR-34c mimics added during IVM on the resulting blastocysts indicate its pivotal role in oocyte competence.

A high-order focus interaction model and oral ulcer dataset for oral ulcer segmentation.

Computer-aided diagnosis has been slow to develop in the field of oral ulcers. One of the major reasons for this is the lack of publicly available datasets. However, oral ulcers have cancerous lesions and their mortality rate is high. The ability to recognize oral ulcers at an early stage in a timely and effective manner is a very critical issue. In recent years, although there exists a small group of researchers working on these, the datasets are private. Therefore to address this challenge, in this paper a multi-tasking oral ulcer dataset (Autooral) containing two major tasks of lesion segmentation and classification is proposed and made publicly available. To the best of our knowledge, we are the first team to make publicly available an oral ulcer dataset with multi-tasking. In addition, we propose a novel modeling framework, HF-UNet, for segmenting oral ulcer lesion regions. Specifically, the proposed high-order focus interaction module (HFblock) performs acquisition of global properties and focus for acquisition of local properties through high-order attention. The proposed lesion localization module (LL-M) employs a novel hybrid sobel filter, which improves the recognition of ulcer edges. Experimental results on the proposed Autooral dataset show that our proposed HF-UNet segmentation of oral ulcers achieves a DSC value of about 0.80 and the inference memory occupies only 2029 MB. The proposed method guarantees a low running load while maintaining a high-performance segmentation capability. The proposed Autooral dataset and code are available from  https://github.com/wurenkai/HF-UNet-and-Autooral-dataset .

[Effect of triptolide on reproductive toxicity in female rats with â ¡ type collagen induced arthritis].

In order to study the toxic effect and mechanism of triptolide(TP) on the reproductive system of female rats with Ⅱ type collagen induced arthritis(CIA), 50 SD rats were randomly divided into normal control group, CIA model group, and three groups receiving TP tablets at clinically equivalent doses of 0. 5, 1, and 2 times, respectively(with TP dosages of 3. 75, 7. 5, and 15 µg·kg~(-1)·d~(-1)), each comprising 10 rats. Intragastric administration was started on the day after the first immunization, once a day, for 42 days.The results were taken on the 21st and 42nd days to calculate the uterine and ovarian organ indexes; pathological and morphological changes in uterus and ovaries were observed under a light microscope; and the levels of estradiol(E_2) and cytochrome P450A1(aromatase,CYP19A1) in ovarian homogenate were detected by ELISA. Furthermore, immunohistochemistry was employed to detect the expression levels of transforming growth factor ß3( TGFß3) pathway-related proteins, mothers against decapentaplegic homolog 3(Smad3) and steroidogenic factor-1(SF-1) in ovarian tissues. In vitro, the mouse Chinese hamster ovary(CHO) cell line was established, and after 24 hours of TP administration(30, 60, 120 nmol·L~(-1)), cell proliferation was detected by the thiazolyl blue tetrazolium bromide(MTT) method, apoptosis by the flow cytometry, and TGFß3, Smad3 and SF-1 protein expression in cells by the Western blot method, and the nuclear entry of SF-1 was detected by immunofluorescence. The results showed that compared with the CIA model group, all TP administration groups showed decreased number of uterine glands, total follicles, mature follicles, and corpus luteum on days 21 and 42 of administration, but there was no statistical difference, and only the administration of 2 times the clinically equivalent dose of TP could significantly increase the number of atretic follicles at 42 days of administration. TP at 3. 75 µg·kg-1·d-1significantly reduced the level of E_2 at 21 days of administration and the expression of TGFß3 and Smad3 factors in ovarian tissues,but had no significant effect on the rate-limiting enzyme in estrogen synthesis CYP19A1. TP at 7. 5 and 15 µg·kg~(-1)·d~(-1) significantly reduced the expression of SF-1 regardless of administration for 21 days or 42 days. TP can significantly promote ovarian cell apoptosis in vitro, with apoptosis mainly concentrated in the late stage of apoptosis after 24 hours of administration. In addition, 60 nmol·L~(-1) TP significantly reduced the protein expression of TGFß3, Smad3 and SF-1 in a dose-dependent manner. In summary, intragastric administration of TP at less than 2 times the clinically equivalent dose for 21 days and 42 days did not cause obvious reproductive damage to the uterus and ovarian tissues of CIA rats, and the number of atretic follicles changed significantly only when the 2 times the clinically equivalent dose was administered for 42 days. TP exerted reproductive toxicity in vivo on reproductive target organs and in vitro on ovarian cells by inhibiting the expression of TGFß3/Smad3/SF-1 pathway.

[Spatio-temporal Differentiation of County Carbon Budget and Territorial Space Optimization Zoning Strategy in Gansu Province from the Perspective of Carbon Neutrality].

Under the background of comprehensively practicing the overall system concept of the "living community" in the new era, incorporating the carbon neutral development goal into the territorial spatial planning and construction and establishing the territorial spatial pattern and optimization strategy in line with the actual development of Gansu Province are of great significance for promoting the comprehensive green low-carbon transformation and high-quality development of regional economy and society. Taking counties in Gansu Province as an example, based on the perspective of carbon neutrality research, the land use carbon budget of 87 counties in Gansu Province in 2010, 2015, and 2021 was calculated and analyzed. GIS spatial analysis and social network analysis were used to further explore their spatial differentiation characteristics and the overall characteristics of the carbon emission spatial correlation network. At last, combined with the main function zoning, the low-carbon oriented land space optimization zoning was carried out, and differentiated low-carbon development strategies were proposed. The results were as follows： ① Carbon emissions in Gansu Province showed an upward trend, but the increase rate decreased, showing a spatial distribution of "high in the central and eastern part of the country, low in the southwest." Construction land was the main carbon source. The carbon uptake showed a spatial distribution of "high in the south and low in the north, high in the west and low in the east." Woodlands were the main carbon sinks. The net carbon emissions showed an increasing trend, and approximately 58.62% of the counties in the province were in a carbon imbalance situation. ② In 2021, the spatial network of county carbon emissions was closely related, showing a "core-edge" pattern. The Chenguan District and Qilihe District were in the core position of the network and received more correlation relationships in the network. The network contacts in Longzhong area were frequent, followed by the contacts in Longdongnan area. ③ Based on carbon emissions, carbon sequestration, and ecological carrying capacity coefficients and using the results of spatial correlation of social networks as role positions, the province was divided into four carbon-neutral sub-districts. At the same time, superimposed analysis of the main function zoning, the county area of the province was reconstructed into seven territorial space zones, and the differentiated regional low-carbon optimization development strategy was proposed for each zone.

Stretchable and Self-Powered Mechanoluminescent Triboelectric Nanogenerator Fibers toward Wearable Amphibious Electro-Optical Sensor Textiles.

Flexible electro-optical dual-mode sensor fibers with capability of the perceiving and converting mechanical stimuli into digital-visual signals show good prospects in smart human-machine interaction interfaces. However, heavy mass, low stretchability, and lack of non-contact sensing function seriously impede their practical application in wearable electronics. To address these challenges, a stretchable and self-powered mechanoluminescent triboelectric nanogenerator fiber (MLTENGF) based on lightweight carbon nanotube fiber is successfully constructed. Taking advantage of their mechanoluminescent-triboelectric synergistic effect, the well-designed MLTENGF delivers an excellent enhancement electrical signal of 200% and an evident optical signal whether on land or underwater. More encouragingly, the MLTENGF device possesses outstanding stability with almost unchanged sensitivity after stretching for 200%. Furthermore, an extraordinary non-contact sensing capability with a detection distance of up to 35 cm is achieved for the MLTENGF. As application demonstrations, MLTENGFs can be used for home security monitoring, intelligent zither, traffic vehicle collision avoidance, and underwater communication. Thus, this work accelerates the development of wearable electro-optical textile electronics for smart human-machine interaction interfaces.

Successful treatment for an adult with bilateral posterior teeth crossbite by miniscrew-assisted rapid palatal expansion: A case report.

Key Clinical Message: Successful treatment by miniscrew-assisted rapid expansion and clinical aligner therapy for an adult diagnosed with maxillary transverse deficiency (MTD) by clinical examinations and Yonsei transverse analysis. Abstract: Adult orthodontic diagnosis and treatment with maxillary transverse deficiency (MTD) is challenging. Miniscrew-assisted rapid palatal expansion (MARPE) is a fast and low-risk method to expand the width of maxillary basal bone. This case report describes a 23-year-old female with mandible deviation and bilateral posterior teeth crossbite. She was diagnosed as MTD by the clinical examinations and Yonsei transverse analysis, and treated by the MARPE and clinical aligner therapy. After 26 months' treatment, cone-beam computed tomography (CBCT) images showed that the width of maxillary basal bone increased by 3.8 mm, that of zygomatic arch and nasal bone increased by 1.0 and 1.9 mm, respectively, and the bilateral posterior teeth crossbite was corrected. Furthermore, the dental midline of lower arch was consistent with that of upper arch and face, the molars arrived Angle Class II and canines was Class I relationships, the profile was maintained, the facial asymmetry was improved. The results of seventeen-month follow-up showed that the effect of orthodontic treatment is very stable. This case report demonstrates that MARPE is the effective approach for patients with MTD and facial asymmetry, which provide the alternative for the treatment of similar cases.

Circular RNAs from bovine blastocysts can interact with miRNAs/tsRNAs from embryonic extracellular vesicles and regulate hatching.

Circular RNAs (circRNAs) are endogenous biological macromolecules that regulate various biological processes including embryo development. However, little is known about which circRNAs are present in bovine preimplantation embryos and their respective roles. Here, we characterized the expression profile of circRNAs in bovine blastocysts for the first time. We detected 25,700 circRNAs in total, with 12,630 circRNAs uniquely expressed in blastocysts compared to degenerated embryos. CircRNA alternative splicing (AS) events were also found more frequently in blastocysts than in degenerated embryos (299 vs 258). Additionally, 410 circRNAs, among which 11 circRNAs with a high potential to encode polypeptides, were found differentially expressed between blastocysts and degenerated embryos. We further predicted and constructed a circRNA-miRNA-mRNA network, wherein differentially expressed circRNAs were shown to bind to bovine preimplantation embryo development-related miRNAs. Employing bioinformatic algorithms we found that differentially expressed circRNAs are associated with differentially expressed miRNAs and transfer RNA-derived small RNAs (tsRNAs) enclosed in embryonic extracellular vesicles (EVs). Furthermore, functional analysis revealed that knockdown of the evolutionarily conserved circAGO2 can inhibit blastocyst hatching. Overall, our study provides the first landscape of circRNAs in bovine preimplantation embryos and highlights the novel role of circRNAs as tsRNA binding partners influencing small RNA sorting and loading into EVs, with circAGO2 playing a regulatory role in bovine blastocyst hatching.

Microstructure Evolution of TB18 Alloy after Thermal Treatment and the Effect of Recrystallization Texture on Mechanical Properties.

In industrial production, the deformation inhomogeneity after metal forging affects the mechanical properties of various parts of the forgings. The question of whether the organization and mechanical properties of ß-titanium alloy can be improved by controlling the amount of forging deformation needs to be answered. Therefore, in this paper, a new sub-stable ß-Ti alloy TB 18 (Ti-5.3Cr-4.9Mo4.9V-4.3Al-0.9Nb-0.3Fe) was subjected to three different levels of deformation, as well as solid solution-aging treatments, and the variation rules of microstructure and mechanical properties were investigated. During the solid solution process, the texture evolution pattern of the TB18 alloy at low deformation (20-40%) is mainly rotational cubic texture deviated into α-fiber texture; at high deformation (60%), the main components of the deformed texture are α-fiber texture with a specific orientation of (114)<113-3>. After subsequent static recrystallization, the α-fiber texture is deviated to an α*-fiber texture, while the specific orientation (114)<113-3> can still be inherited as a major component of the recrystallized texture. The plasticity of the alloy in the normal direction (ND) after the solid solution is influenced by the existence of the <110>//ND texture, and the plasticity of the alloy in the ND direction after aging is determined by a combination of the volume fraction of the <110>//ND texture in the matrix phase and the volume fraction of [112-0]α//ND in the α phase. The results show that it is feasible to change the characteristics of the recrystallization texture of TB18 by controlling the deformation level of hot forging, thus realizing the modulation of the mechanical properties.

Stable and wavelength-tunable multiwavelength laser for high-rate measurement device independent quantum key distribution.

Measurement device independent quantum key distribution (MDI QKD) has attracted growing attention for its immunity to attacks at the measurement unit, but its unique structure limits the secret key rate. Utilizing the wavelength division multiplexing (WDM) technique and reducing error rates are effective strategies for enhancing the secret key rate. Reducing error rates often requires active feedback control of wavelengths using precise external references. However, for a multiwavelength laser, employing multiple references to stabilize each wavelength output places stringent demands on these references and significantly increases system complexity. Here, we demonstrate a stable, wavelength-tunable multiwavelength laser with an output wavelength ranging from 1270 to 1610 nm. Through precise temperature control and stable drive current, we passively lock the laser wavelength, achieving remarkable wavelength stability. This significantly reduce the error rate, leading to an almost doubling of the secret key rate compared to previous experiments. Furthermore, the exceptional wavelength stability offered by our multiwavelength laser, combined with the WDM technique, has further boosted the secret key rate of MDI QKD. With a wide wavelength tuning range of 5.1 nm, our multiwavelength laser facilitates flexible operation across multiple dense wavelength division multiplexing channels. Coupled with high wavelength stability and multiple wavelength outputs simultaneously, this laser offers a promising solution for a high-rate MDI QKD system.

Selection and application of small non-coding RNAs for normalizing RT-qPCR data of bovine preimplantation embryo conditioned medium.

Small non-coding RNAs (sncRNAs) present in the conditioned medium (CM) of bovine preimplantation embryos are potential noninvasive biomarkers for assessing embryo quality. Accurate quantification of sncRNA levels in the spent CM is of utmost importance in this regard. RT-qPCR is considered as the gold standard for quantifying RNA. In order to standardize RT-qPCR data in the sample type under investigation, the use of suitable stable sncRNAs is essential. Here, we selected 10 sncRNAs from small RNA sequencing of CM samples derived from both bovine blastocysts and degenerate embryos, and evaluated their expression stability together with that of cel-miR-39 as a spike and the often-used U6 small nuclear RNA at different embryo developmental stages. In CM of 2-cell embryos, rsRNA-1044 showed the most stable expression, while tDR-1:32-Gly-CCC-1 was the most stable expressed sncRNA in CM of the stages beyond the 2-cell stage. Next, tDR-1:32-Gly-CCC-1 was used for normalizing the RT-qPCR data from the CM of blastocysts and degenerate embryos. Bta-miR-155 and tDR-39:75-Arg-CCG-2 were found to be significantly up-regulated in the CM of blastocysts compared to that of the degenerated embryos (P = 0.028 and P = 0.017, respectively), suggesting their expression levels are related to embryo development stage. In conclusion, tDR-1:32-Gly-CCC-1 can serve as a suitable reference sncRNA for normalization of RT-qPCR data of the CM from bovine blastocysts.

Jinlida for Diabetes Prevention in Impaired Glucose Tolerance and Multiple Metabolic Abnormalities: The FOCUS Randomized Clinical Trial.

Importance: Previous studies have shown that Jinlida (JLD) granules, an approved treatment for type 2 diabetes in China, can reduce blood glucose level, reduce glycated hemoglobin (HbA1c), and improve insulin resistance in people with type 2 diabetes. Objective: To evaluate the effect of long-term administration of JLD vs placebo on the incidence of diabetes in participants with impaired glucose tolerance (IGT) and multiple metabolic abnormalities. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial (FOCUS) was conducted across 35 centers in 21 cities in China from June 2019 to February 2023. Individuals aged 18 to 70 years with IGT and multiple metabolic abnormalities were enrolled. Intervention: Participants were randomly allocated 1:1 to receive JLD or placebo (9 g, 3 times per day, orally). They continued this regimen until they developed diabetes, withdrew from the study, were lost to follow-up, or died. Main Outcomes and Measures: The primary outcome was the occurrence of diabetes, which was determined by 2 consecutive oral glucose tolerance tests. Secondary outcomes included waist circumference; fasting and 2-hour postprandial plasma glucose levels; HbA1c; fasting insulin level; homeostatic model assessment for insulin resistance (HOMA-IR); total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels; ankle-brachial index; and carotid intima-media thickness. Results: A total of 889 participants were randomized, of whom 885 were in the full analysis set (442 in the JLD group; 443 in the placebo group; mean [SD] age, 52.57 [10.33] years; 463 [52.32%] female). Following a median observation period of 2.20 years (IQR, 1.27-2.64 years), participants in the JLD group had a lower risk of developing diabetes compared with those in the placebo group (hazard ratio, 0.59; 95% CI, 0.46-0.74; P < .001). During the follow-up period, the JLD group had a between-group difference of 0.95 cm (95% CI, 0.36-1.55 cm) in waist circumference, 9.2 mg/dL (95% CI, 5.4-13.0 mg/dL) in 2-hour postprandial blood glucose level, 3.8 mg/dL (95% CI, 2.2-5.6 mg/dL) in fasting blood glucose level, 0.20% (95% CI, 0.13%-0.27%) in HbA1c, 6.6 mg/dL (95% CI, 1.9-11.2) in total cholesterol level, 4.3 mg/dL (95% CI, 0.8-7.7 mg/dL) in low-density lipoprotein cholesterol level, 25.7 mg/dL (95% CI, 15.9-35.4 mg/dL) in triglyceride levels, and 0.47 (95% CI, 0.12-0.83) in HOMA-IR compared with the placebo group. After 24 months of follow-up, the JLD group had a significant improvement in ankle-brachial index and waist circumference compared with the placebo group. Conclusions and Relevance: The findings suggest that JLD can reduce the risk of diabetes in participants with IGT and multiple metabolic abnormalities. Trial Registration: Chinese Clinical Trial Register: ChiCTR1900023241.

Changes in phenolic compounds of Phyllanthus emblica juice during different storage temperature and pH conditions.

The aim of this experiment was to investigate the effect of storage temperature and pH on phenolic compounds of Phyllanthus emblica juice. Juice was stored at different temperatures and pH for 15 days and sampled on 2-day intervals. The browning index (BI, ABS420 nm), pH, centrifugal precipitation rate (CPR), and phenolic compounds were evaluated. The results showed 4°C and pH 2.5 could effectively inhibit browning and slow down pH drop of P. emblica juice. The result of orthogonal partial least square-discriminant analysis showed P. emblica juice stored at 4°C and pH 2.5 still had a similar phenolic composition, but at 20°C, 37°C, and pH 3.5, the score plots were concentrated only in the first 3 days. Additionally, gallic acid (GA) and ellagic acid (EA) were screened out to be the differential compounds for browning of P. emblica juice. The contents of GA, epigallocatechin (EGC), corilagin (CL), gallocatechin gallate (GCG), chebulagic acid (CA), 1,2,3,4,6-O-galloyl-d-glucose (PGG), and EA were more stable at 4°C and pH 2.5. Overall, during storage at 4°C and pH 2.5, it could inhibit the increase of GA and EA and decrease of CL, GCG, CA, and PGG, whereas EGC did not show significant difference between storage conditions. The CPR was higher at 4°C, while pH 2.5 could reduce the CPR. In conclusion, in order to maintain stability of phenolic compounds and extended storage period, the P. emblica juice could be stored at low temperature and adjust the pH to increase the stability of juice system.

Placental inflammatory injury induced by chlorinated polyfluorinated ether sulfonate (F-53B) through NLRP3 inflammasome activation.

Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6 J female mice were randomly allocated to three groups: the control group, F-53B 0.8 µg/kg/day group, and F-53B 8 µg/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5-14.5, the F-53B 8 µg/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8 µg/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1ß, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B.

Acid-Activated TAT Peptide-Modified Biomimetic Boron Nitride Nanoparticles for Enhanced Targeted Codelivery of Doxorubicin and Indocyanine Green: A Synergistic Cancer Photothermal and Chemotherapeutic Approach.

The evolution of nano-drug delivery systems addresses the limitations of conventional cancer treatments with stimulus-responsive nanomaterial-based delivery systems presenting temporal and spatial advantages. Among various nanomaterials, boron nitride nanoparticles (BNNs) demonstrate significant potential in drug delivery and cancer treatment, providing a high drug loading capacity, multifunctionality, and low toxicity. However, the challenge lies in augmenting nanomaterial accumulation exclusively within tumors while preserving healthy tissues. To address this, we introduce a novel approach involving cancer cell membrane-functionalized BNNs (CM-BIDdT) for the codelivery of doxorubicin (Dox) and indocyanine green to treat homologous tumor. The cancer cell membrane biomimetic CM-BIDdT nanoparticles possess highly efficient homologous targeting capabilities toward tumor cells. The surface modification with acylated TAT peptides (dTAT) further enhances the nanoparticle intracellular accumulation. Consequently, CM-BIDdT nanoparticles, responsive to the acidic tumor microenvironment, hydrolyze amide bonds, activate the transmembrane penetrating function, and achieve precise targeting with substantial accumulation at the tumor site. Additionally, the photothermal effect of CM-BIDdT under laser irradiation not only kills cells through thermal ablation but also destroys the membrane on the surface of the nanoparticles, facilitating Dox release. Therefore, the fabricated CM-BIDdT nanoparticles orchestrate chemo-photothermal combination therapy and effectively inhibit tumor growth with minimal adverse effects, holding promise as a new modality for synergistic cancer treatment.

Effectivenss of electroacupuncture for skeletal muscle pain in Parkinson's disease: a Clinical randomized controlled trial.

OBJECTIVE: To explore the effect of electroacupuncture on skeletal muscle pain in Parkinson's disease (PD). METHODS: A single-center randomized controlled trial was conducted with sixty patients with Parkinson's disease with skeletal muscle pain were randomly divided into electroacupuncture group and sham acupuncture control group with 30 patients each. The electric acupuncture group was treated with electric acupuncture, while the control group was treated with Park needle pseudoacupuncture. Both groups were treated 5 times a week for a total of 4 weeks, and both groups completed 20 treatments. King's Parkinson's Pain Scale (KPPS) and visual analog scale (VAS) were used before and after treatment to evaluate the pain degree of patients. Real-time shear wave elastography (SWE) and modified Ashworth score (MAS) were used to evaluate the changes of muscle tone. Parkinson's comprehensive Score Scale (MDS-UPDRS, including UPDRSⅡ and UPDRS Ⅲ) was used to evaluate exercise ability. Hamilton Depression Scale (HAMD) score was used to evaluate the emotional changes of patients. Spearman correlation analysis was used to explore the correlation between pain degree and muscle tone, exercise ability and emotion. RESULTS: During the study, one case fell off in the control group, and 30 cases were eventually included in the analysis and treatment group and 29 cases in the control group. After treatment, Young's modulus of biceps and quadriceps and shear wave velocity of biceps were decreased in electroacupuncture group compared with before treatment, while KPPS score, VAS score, UPDRSⅡ, UPDRS Ⅲ and modified Ashworth score were decreased, with statistical significance (P < 0.05). There was no statistical significance in control group (P > 0.05). After treatment, KPPS score, VAS score, UPDRSⅡ and UPDRS Ⅲ, MAS, HAMD score, Young's modulus of biceps and shear wave velocity in electroacupuncture group were significantly lower than those in control group (P < 0.05). Spearman correlation analysis showed that KPPS score was positively correlated with UPDRS Ⅲ (r = 0.414, P < 0.05). KPPS score was positively correlated with HAMD score (r = 0.576, P < 0.01). CONCLUSION: Electroacupuncture therapy can effectively improve skeletal muscle pain in patients with Parkinson's disease, reduce the muscle hardness of patients, improve patients' daily life ability, and improve patients' emotional disorders. The degree of skeletal muscle pain in PD patients is correlated with motor ability and emotional disorders, but there is no significant correlation between the degree of skeletal muscle pain and the muscle tone of PD patients.

[Ecological network optimization of Jiuquan City, Gansu, China based on complex network theory and circuit model]. / åŸºäºŽå¤æ‚ç½‘ç»œç†è®ºå’Œç”µè·¯æ¨¡åž‹çš„é ’æ³‰å¸‚ç”Ÿæ€ç½‘ç»œä¼˜åŒ–.

Building a scientific and reasonable ecological network is the key for optimizing the pattern of territorial development and protection, and is of great significance for ensuring regional ecological security and promoting the virtuous cycle of ecosystems. In previous studies, nodal attack method (destruction of ecological source area) was often used in the "robustness" evaluation of ecological networks. Actually, the ecological corridor is more fragile than the source area, and thus the nodal attack method is not reasonable. In this study, taking Jiuquan City as the research area, based on the circuit model to construct the ecological network, we carried out the topology optimization of ecological network by using three strategies (random edge increase, node degree and priority edge increase with low node intermedium number) in complex network theory. We compared and analyzed the "robustness" of ecological network before and after optimization by constructing edge attack strategy, and selected the best network optimization strategy. The results showed that 65 ecological source areas were identified in Jiuquan City, with a total area of 20275.15 km2, and that grassland accounted for 89.5% of the source area. We identified 179 ecological corridors with a total length of 6387.16 km, 158 ecological barrier points with a total area of 1385.5 km2. The unused land accounted for 92.2% of the total barrier points area. We identified 63 ecological pinch points, mainly concentrated in the source edge and corridor intersection. Among them, the spatial distribution of 11 barrier points and pinch points was consistent, which was the key area to be repaired in ecological network optimization. The three optimization strategies had significantly improved the stability of ecological network in Jiuquan City. The relative size of the maximum connected subgraph and the edge connected rate of the ecological network of the optimization strategy of adding edges according to degree were all the most stable under random attack mode and deliberate attack mode, which was the best optimization scheme for ecological network in Jiuquan City.

Prediction of complete regression in fertility-sparing patients with endometrial cancer and apical hyperplasia: the GLOBAL model in a large Chinese cohort.

BACKGROUND: Fertility preservation treatment is increasingly essential for patients with apical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) worldwide. Complete regression (CR) is the main endpoint of this treatment. Accurately predicting CR and implementing appropriate interventions during treatment are crucial for these patients. METHODS: We conducted a retrospective study involving 193 patients diagnosed with atypical AEH or EEC, enrolled from January 2012 to March 2022 at our center. We evaluated 24 clinical parameters as candidate predictors and employed LASSO regression to develop a prediction model for CR. Subsequently, a nomogram was constructed to predict CR after the treatment. We evaluated the performance of the nomogram using receiver operator characteristic (ROC) curve and decision curve analysis (DCA) to assess its predictive accuracy. Additionally, we employed cumulative curves to determine the CR rate among patients. RESULTS: Out of the 193 patients, 173 achieved CR after undergoing fertility preservation treatment. We categorized features with similar properties and provided a list of formulas based on their coefficients. The final model, named GLOBAL (including basic information, characteristics, blood pressure, glucose metabolism, lipid metabolism, immunohistochemistry, histological type, and medication), comprised eight variables identified using LASSO regression. A nomogram incorporating these eight risk factors was developed to predict CR. The GLOBAL model exhibited an AUC of 0.907 (95% CI 0.828-0.969). Calibration plots demonstrated a favorable agreement between the predicted probability by the GLOBAL model and actual observations in the cohort. The cumulative curve analysis revealed varying cumulative CR rates among patients in the eight subgroups. Categorized analysis demonstrated significant diversity in the effects of the GLOBAL model on CR among patients with different total points (p < 0.05). CONCLUSION: We have developed and validated a model that significantly enhances the predictive accuracy of CR in AEH and EEC patients seeking fertility preservation treatment.

tRNAGlu-derived fragments from embryonic extracellular vesicles modulate bovine embryo hatching.

Transfer RNA-derived small RNAs (tsRNAs) have been shown to be involved in early embryo development and repression of endogenous retroelements in embryos and stem cells. However, it is unknown whether tsRNAs also regulate embryo hatching. In this study, we mined the sequencing data of a previous experiment in which we demonstrated that the microRNA (miRNA) cargo of preimplantation embryonic extracellular vesicles (EVs) influences embryo development. We thus profiled the tsRNA cargo of EVs secreted by blastocysts and non-blastocysts. The majority of tsRNAs was identified as tRNA halves originating from the 5´ ends of tRNAs. Among the 148 differentially expressed tsRNAs, the 19 nt tRNA fragment (tRF) tDR-14:32-Glu-CTC-1 was found to be significantly up-regulated in EVs derived from non-blastocysts. RT-qPCR assays confirmed its significant up-regulation in non-blastocyst embryos and their conditioned medium compared to the blastocyst group (P < 0.05). Inhibition of tDR-14:32-Glu-CTC-1 by supplementing antagomirs to the conditioned medium improved embryo hatching (P < 0.05). Transcriptomic analysis of embryos treated with tDR-14:32-Glu-CTC-1 antagomirs further showed differential expression of genes that are associated with embryo hatching and implantation. In summary, tDR-14:32-Glu-CTC-1 is up-regulated in non-blastocyst embryos and their secretions, and inhibition of tDR-14:32-Glu-CTC-1 promotes embryo hatching, while influencing embryo implantation-related genes and pathways. These results indicate that embryonic EVs containing specific tRFs may regulate preimplantation embryo development.

Clinical evaluation of photodynamic therapy for oral leukoplakia: a retrospective study of 50 patients.

BACKGROUND: Topical photodynamic therapy (PDT) has demonstrated encouraging results in the treatment of oral leukoplakia (OLK). However, data on the clinical efficacy of PDT in Chinese patients with OLK are still limited. METHODS: Fifty patients diagnosed with OLK were enrolled, including patients with various dysplastic tissues. All patients received topical PDT with 5-aminolevulinic acid (5-ALA) as a photosensitizer. Clinical efficacy was evaluated 4 weeks after treatment. Follow-up was performed every 3 months during the first year and every 6 months during the second year. RESULTS: The overall response rate was 68% (34/50): 12% (n = 6) complete and 56% (n = 28) partial responses. Aneuploidy was reduced in the patients with dysplastic lesions. Oral pain and local ulcers developed in 52% of the patients (n = 26). Patients with a long history of OLK including hyperplasia and dysplastic lesions, as well as those with non-homogenous lesions, were more likely to develop pain and ulcer. During follow-up, the recurrence rate of hyperplasia and dysplastic lesions was 32% (n = 16) and the malignant transformation rate of dysplastic lesions was 4% (n = 2). Lesions on the buccal mucosa were associated with recurrence (P = 0.044; OR: 0.108, 95% CI: 0.013-0.915). CONCLUSION: Topical 5-ALA-mediated PDT is an effective treatment for OLK, particularly for homogenous leukoplakia, with few side effects. The buccal mucosa may be a protective factor that can reduce recurrence.