OsMAPK6 phosphorylation and CLG1 ubiquitylation of GW6a non-additively enhance rice grain size through stabilization of the substrate.

The chromatin modifier GRAIN WEIGHT 6a (GW6a) enhances rice grain size and yield. However, little is known about its gene network determining grain size. Here, we report that MITOGEN-ACTIVED PROTEIN KINASE 6 (OsMAPK6) and E3 ligase CHANG LI GENG 1 (CLG1) interact with and target GW6a for phosphorylation and ubiquitylation, respectively. Unexpectedly, however, in vitro and in vivo assays reveal that both of the two post-translational modifications stabilize GW6a. Furthermore, we uncover two major GW6a phosphorylation sites (serine142 and threonine186) targeted by OsMAPK6 serving an important role in modulating grain size. In addition, our genetic and molecular results suggest that the OsMAPK6-GW6a and CLG1-GW6a axes are crucial and operate in a non-additive manner to control grain size. Overall, our findings identify a previously unknown mechanism by which phosphorylation and ubiquitylation non-additively stabilize GW6a to enhance grain size, and reveal correlations and interactions of these posttranslational modifications during rice grain development.

[Experimental study on improvement of cognitive impairment in Alzheimer's disease by different degrees of steaming and sunning of Polygoni Multiflori Radix based on fecal metabolomics].

The fecal metabolomics method was employed to investigate the cognitive improvement mechanism of Polygoni Multiflori Radix in Alzheimer's disease(AD) and examine the effects of different degrees of steaming and sunning on cognitive function in AD model mice. Additionally, the processing principle of Polygoni Multiflori Radix was discussed. Forty-eight 5-month-old APP/PS1 mice were randomly assigned to the following groups: model group, positive group, raw product group, three-steaming and three-sunning product group, six-steaming and six-sunning product group, and nine-steaming and nine-sunning product group. Seven negative control mice from the same litter were included as the blank group. After 150 days of intragastric administration, the learning and memory abilities of mice in each group were assessed by using the Barnes maze and dark avoidance tests. Fecal samples were collected for extensive targeted metabolomics testing. Principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA), and other multivariate statistical methods were utilized to analyze metabolites in mouse feces. Comparison of behavioral results between the model group and different product groups demonstrated that the six-steaming and six-sunning product group exhibited significantly reduced latency in the Barnes maze positioning and navigation test(P<0.05), as well as a notable decrease in the number of errors in the space exploration experiment(P<0.05). Moreover, the latency of mice entering the dark box for the first time in the dark avoidance experiment was significantly prolonged(P<0.05), indicating the best overall improvement in the learning and memory ability of AD model mice. Metabolomics results revealed that compared with the model group, the differential metabolites in other groups in descending order were as follows: six-steaming and six-sunning product group > nine-steaming and nine-sunning product group > raw product group > three-steaming and three-sunning product group, encompassing 146, 120, 95, and 81 potential biomarkers, respectively. Among them, 16 differential metabolites were related to AD disease. Further comparisons based on the degree of processing indicated that the six-steaming and six-sunning product group exhibited the most significant adjustments in total metabolic pathways, particularly regulating the interconversion of pentose and glucuronic acid, as well as amino acid anabolism and other pathways. In summary, the mechanism of Polygoni Multiflori Radix after processing in enhancing the learning and memory ability of APP/PS1 mice may be associated with improved amino acid metabolism and increased energy metabolism in the body. The six-steaming and six-sunning yielded the best outcomes.

ASSOCIATION OF MACULAR STRUCTURE WITH MICROPERIMETRY SENSITIVITY FOLLOWING VITRECTOMY FOR PROLIFERATE DIABETIC RETINOPATHY.

PURPOSE: To evaluate macular sensitivity using microperimetry in patients with proliferate diabetic retinopathy following vitrectomy and to investigate the relationship between the sensitivity and foveal microstructures with optical coherence tomography/angiography. METHODS: Eighty-four eyes of 84 patients with proliferative diabetic retinopathy, who were indicated for vitrectomy, had no intraocular surgery history 3 months preoperatively, and were able to ensure fundus examination after the vitrectomy, were included. A logMAR best-corrected visual acuity, macular sensitivity of microperimetry, macular retinal thickness, and macular vessel perfusion using optical coherence tomography/angiography were examined at 1 week, 1 month, and 3 months postoperatively. RESULTS: The logMAR best-corrected visual acuity and mean macular sensitivity of patients with proliferative diabetic retinopathy improved postoperatively (P < 0.05). There was a significant correlation between best-corrected visual acuity and mean sensitivity (P < 0.05). Postoperative mean macular sensitivity was significantly correlated with outer retinal thickness in the 0 to 6 mm macular area (P < 0.05) and also significantly correlated with deep capillary plexus perfusion (P < 0.05). Fixation stability and mean macular sensitivity did not show any correlation with glycated hemoglobin, triglyceride, serum total cholesterol, carbamide, and creatinine and duration of diabetes mellitus (P > 0.05). CONCLUSION: Postoperative mean macular sensitivity was significantly correlated with outer retinal thickness and deep capillary plexus perfusion for patients with proliferative diabetic retinopathy. The authors found that the visual performance of patients can be evaluated by the outer retinal thickness and deep capillary plexus perfusion, so optical coherence tomography/angiography examination can be an important prognostic factor for visual performance in patients.Clinical Trial Registration: This trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn; Registration No.: ChiCTR2100043399).

Macrophage-derived ectosomal miR-350-3p promotes osteoarthritis progression through downregulating chondrocyte H3K36 methyltransferase NSD1.

Mechanical overloading can promote cartilage senescence and osteoarthritis (OA) development, but its impact on synovial macrophages and the interaction between macrophages and chondrocytes remain unknown. Here, we found that macrophages exhibited M1 polarization under mechanical overloading and secreted ectosomes that induced cartilage degradation and senescence. By performing miRNA sequencing on ectosomes, we identified highly expressed miR-350-3p as a key factor mediating the homeostatic imbalance of chondrocytes caused by M1-polarized macrophages, this result being confirmed by altering the miR-350-3p level in chondrocytes with mimics and inhibitor. In experimental OA mice, miR-350-3p was increased in synovium and cartilage, while intra-articular injection of antagomir-350-3p inhibited the increase of miR-350-3p and alleviated cartilage degeneration and senescence. Further studies showed that macrophage-derived ectosomal miR-350-3p promoted OA progression by inhibiting nuclear receptor binding SET domain protein 1(NSD1) in chondrocytes and regulating histone H3 lysine 36(H3K36) methylation. This study demonstrated that the targeting of macrophage-derived ectosomal miRNAs was a potential therapeutic method for mechanical overload-induced OA.

Gut Microbiome-Serum Metabolism Revealed the Allergenicity of Ferulic Acid Combined with Glucose-Modified ß-Lactoglobulin.

A novel strategy combining ferulic acid and glucose was proposed to reduce ß-lactoglobulin (BLG) allergenicity and investigate whether the reduction in allergenicity was associated with gut microbiome and serum metabolism. As a result, the multistructure of BLG changed, and the modified BLG decreased significantly the contents of IgE, IgG, IgG1, and mMCP-1 in serum, improved the diversity and structural composition of gut microbiota, and increased the content of short-chain fatty acids (SCFAs) in allergic mice. Meanwhile, allergic mice induced by BLG affected arachidonic acid, tryptophan, and other metabolic pathways in serum, the modified BLG inhibited the production of metabolites in arachidonic acid metabolism pathway and significantly increased tryptophan metabolites, and this contribution helps in reducing BLG allergenicity. Overall, reduced allergenicity of BLG after ferulic acid was combined with glucose modification by regulating gut microbiota, the metabolic pathways of arachidonic acid and tryptophan. The results may offer new thoughts alleviating the allergy risk of allergenic proteins.

Suspected duloxetine-induced restless legs syndrome phenotypic variant: a case report.

BACKGROUND: Restless arms syndrome (RAS) is the most common variant of restless legs syndrome (RLS), which is easy to be ignored in clinical practice due to the lack of specific diagnostic criteria. When effective therapeutic agents induced RAS and symptoms persisted after briefly observation, clinicians will face the challenge of weighing efficacy against side effects. CASE PRESENTATION: A 67-year-old woman was admitted to a geriatric psychiatric ward with depression. Upon admission, the escitalopram dose was reduced from 15 mg to 10 mg per day, and the duloxetine dose was increased from 60 mg to 80 mg per day. The next night before bedtime, she developed itching and creeping sensations deep inside bilateral shoulders and arms, with the urge to move, worsening at rest, and alleviation after hammering. The symptoms persisted when escitalopram was discontinued. A history of RLS was confirmed. Treatment with 40 mg of duloxetine and 0.125 mg of pramipexole significantly improved depression, and the paresthesia disappeared, with no recurrence occurring 6 months after discharge. DISCUSSION AND CONCLUSIONS: This case suggests that psychiatrists should pay attention to RLS variants when increasing doses of duloxetine. Long-term improvement can be achieved through dosage reduction combined with dopaminergic drugs instead of immediate discontinuation.

Efficacy and Safety of Bufei Jiedu Granules in Treating Multidrug-Resistant Pulmonary Tuberculosis: A Multi-center, Double-Blinded and Randomized Controlled Trial.

OBJECTIVE: To assess the efficacy and safety of Bufei Jiedu (BFJD) ranules as adjuvant therapy for patients with multidrug-resistant pulmonary tuberculosis (MDR-PTB). METHODS: A large-scale, multi-center, double-blinded, and randomized controlled trial was conducted in 18 sentinel hospitals in China from December 2012 to December 2016. A total of 312 MDR-PTB patients were randomly assigned to BFJD Granules or placebo groups (1:1) using a stratified randomization method, which both received the long-course chemotherapy regimen for 18 months (6 Am-Lfx-P-Z-Pto, 12 Lfx-P-Z-Pto). Meanwhile, patients in both groups also received BFJD Granules or placebo twice a day for a total of 18 months, respectively. The primary outcome was cure rate. The secondary outcomes included time to sputum-culture conversion, changes in lung cavities and quality of life (QoL) of patients. Adverse reactions were monitored during and after the trial. RESULTS: A total of 216 cases completed the trial, 111 in the BFJD Granules group and 105 in the placebo group. BFJD Granules, as an adjuvant treatment, increased the cure rate by 13.6% at the end of treatment, compared with the placebo (58.4% vs. 44.8%, P=0.02), and accelerated the median time to sputum-culture conversion (5 months vs. 11 months). The cavity closure rate of the BFJD Granules group (50.6%, 43/85) was higher than that of the placebo group (32.1%, 26/81; P=0.02) in patients who completed the treatment. At the end of the intensive treatment, according to the 36-item Short Form, the BFJD Granules significantly improved physical functioning, general health, and vitality of patients relative to the placebo group (all P<0.01). Overall, the death rates in the two groups were not significantly different; 5.1% (8/156) in the BFJD Granules group and 2.6% (4/156) in the placebo group. CONCLUSIONS: Supplementing BFJD Granules with the long-course chemotherapy regimen significantly increased the cure rate and cavity closure rates, and rapidly improved QoL of patients with MDR-PTB (Registration No. ChiCTR-TRC-12002850).

Stretchable Electrodes with Interfacial Percolation Network.

Stretchable electrodes are an essential component that determines the functionality and reliability of stretchable electronics, but face the challenge of balancing conductivity and stretchability. This work proposes a new conducting concept called the interfacial percolation network (PN) that results in stretchable electrodes with high conductivity, large stretchability, and high stability. The interfacial PN is composed of a 2D silver nanowires (AgNWs) PN and a protruding 3D AgNWs PN embedded on the surface and in the near-surface region of an elastic polymer matrix, respectively. The protruded PN is obtained by changing the arrangements of AgNWs from horizontal to quasi-vertical through introducing foreign polymer domains in the near-surface region of the polymer matrix. The resulting electrode achieves a conductivity of 13 500 S cm-1 and a stretchability of 660%. Its resistance changes under stretched conditions are orders of magnitude lower than those of conventional 2D PN and 2D + 3D PN. An interfacial PN electrode made from liquid metal remained its conductivity at 46 750 S cm-1 after the electrode underwent multiple stretch-release cycles with a deformation of >600%. The concept of interfacial PN provides fruitful implications for the design of stretchable electronics.

Fully Biodegradable Packaging Films for Fresh Food Storage Based on Oil-Infused Bacterial Cellulose.

Fully biodegradable packaging materials are demanded to resolve the issue of plastic pollution. However, the fresh food storage performance of biodegradable materials is generally much lower than that of plastics due to their high permeability, microbial friendliness, and limited stretchability and transparency. Here a biodegradable packaging material is reported with high fresh food storage performance based on an oil-infused bacterial cellulose (OBC) porous film. The oil infusion significantly improved cellulose's food-keeping performance by reducing its gas permeability, increasing its stretchability and transparency, and enabling the active release of green vapor-phase preservative molecules, while maintaining its intrinsically high degradability. Strawberries stored in a container with the OBC lid at 23 °C after 5 days exhibited a moldy rate of 0%, in contrast to the 100% moldy rate of those stored by poly(ethylene). Enhanced storage performance is also obtained on tomatoes, pork, and shrimp. The OBC film is naturally degraded after being buried in wet soil at 30 °C for 9 days, identical to the degradation rate of bacterial cellulose. The liquid seal strategy broadly applies to different celluloses, providing a general option for developing cellulose-based biodegradable packaging materials.

Incidence, Outcomes, and Risk Factors for Isoniazid-Resistant Tuberculosis from 2012 to 2022 in Eastern China.

BACKGROUND: Isoniazid-resistant, rifampicin-susceptible tuberculosis (Hr-TB) is the most frequent drug-resistant tuberculosis (DR-TB) in the world, and unfavorable outcomes of Hr-TB are more common compared to drug-susceptible TB. Considering there is no optimal regimen accepted worldwide, we undertook a retrospective cohort study in eastern China to estimate incidence trends and risk factors associated with unfavorable outcomes of Hr-TB. METHODS: Between January 2012 and December 2022, all Hr-TB patients' information was extracted from the Tuberculosis Information Management System (TIMS), which is a national electronic information platform, to record TB patients' clinical information in this study. The incidence of Hr-TB was determined by the mid-year population according to census data published by the government. We categorized treatment regimens depending on fluoroquinolone (FQ) use, and potential risk factors were analyzed using multivariable logistic regression. RESULTS: A total of 3116 Hr-TB patients fulfilled the inclusion criteria and were enrolled in this study. The average annual rate of Hr-TB in the 11 years under investigation was 0.34 per 100,000 and increased to 0.53 per 100,000 until 2019. In total, six different treatment regimens were utilized in the study sites, and less than 1% of regimens adopted FQ. There was no difference in the unfavorable outcomes between the FQ-included and FQ-excluded groups (p = 0.22). The average treatment duration was 7.06 months, and the longest treatment was 26 months. Approximately 20% (637/3116) of Hr-TB patients had unfavorable outcomes, and 60.13% (383/637) of them proceeded to multidrug-resistant tuberculosis (MDR-TB). Treatment duration and a positive smear at the end of the 5th month were significantly associated with unfavorable outcomes (p < 0.001). CONCLUSION: The unfavorable treatment outcomes of Hr-TB are still high in eastern China, and the efficacy of FQ-containing regimens needs to be validated for Hr-TB treatment.

Latent tuberculosis infection and infection-associated risk factors for miner workers with silicosis in eastern China.

OBJECTIVES: Silicosis people are at high risk of developing pulmonary tuberculosis. Whether silica exposure increases the likelihood of latent tuberculosis infection (LTBI) was not well understood, and potential factors involved in LTBI risk among silicosis people were not evaluated before. Thus, LTBI among silicosis people and potential risk factors for LTBI among silicosis people were evaluated in this study. METHODS: A cross-sectional study was undertaken for 130 miner workers with silicosis. The QFT-GIT was performed for LTBI detection. RESULTS: The LTBI was high to 31.6% (36/114) for silicosis participants, and 13.1% (13/99) had a history of tuberculosis. Drinking was associated with LTBI risk (OR = 6.92, 95%CI, 1.47-32.66, P = 0.015). Meanwhile, tunneling work was associated with an increased risk of LTBI compared with other mining occupations (OR = 3.91,95%CI,1.20-12.70, P = 0.024). CONCLUSIONS: The LTBI rate of silicosis participants was high and more than 10% had a history of tuberculosis. Drinking alcohol and tunneling were independent risk factors for LTBI in silicosis participants.

Association Between Triglyceride-Glucose Index and Hearing Threshold Shifts of Adults in the United States: National Health and Nutrition Examination Survey, 2015-2016.

Objective: Sensorineural Hearing Loss (SNHL) is a representative human sensory impairment, few studies have paid attention to the correlation between the Triglyceride-Glucose (TyG) index and SNHL to date. We conducted this analysis to elucidate the correlation between the TyG index and pure tone hearing thresholds among US adults. Methods: Our analysis included 1226 adults (age range: 20 to 69 years old) from the 2015-2016 National Health and Nutrition Examination Survey (NHANES) data. TyG index was scored into three quartiles. Weighted univariate analysis, weighted multivariate linear regression analyses as well as smooth curve fittings evaluated the associations between TyG index and pure tone hearing thresholds. Results: In the multiple regression analysis, the second tertile of TyG index was negatively associated with high-frequency hearing thresholds shifts. Furthermore, the non-linear relationships between TyG index and speech-frequency and high-frequency hearing thresholds were identified by smooth curve fittings. After adjusting for potential confounders, the fitted smooth curves were approximately U-shaped, and the two-segment linear regression models were constructed to calculate their inflection points. Conclusion: Our findings suggested that the TyG index was nearly U-shaped association with speech-frequency and high-frequency hearing thresholds. These results may imply the importance of maintaining a balanced TyG index in health management.

Optical coherence tomography biomarkers as outcome predictors to guide dexamethasone implant use in patients with iERM: a randomized controlled trial.

BACKGROUND: We aimed to investigate the anatomical features of optical coherence tomography (OCT) and vitreous cytokine levels as predictors of outcomes of combined phacovitrectomy with intravitreal dexamethasone (DEX) implants for idiopathic epiretinal membrane (iERM) treatment. METHODS: A prospective, single-masked, randomized, controlled clinical trial included 48 eyes. They were randomly assigned in a 1:1 ratio to undergo the DEX group (combined phacovitrectomy with ERM peeling and Ozurdex implantation) and control group (phacovitrectomy only). Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed at 1 d, 1 week, 1 month, and 3 months. The structural features of OCT before surgery were analysed for stratified analysis. Baseline soluble CD14 (sCD14) and sCD163 levels in the vitreous fluid were measured using ELISA. RESULTS: BCVA and CMT were not significantly different in the DEX and control groups. Eyes with hyperreflective foci (HRF) at baseline achieved better BCVA (Ptime*group=0.746; Pgroup=0.043, Wald χ²=7.869) and lower CMT (Ptime*group = 0.079; Pgroup = 0.001, Wald χ²=6.774) responses to DEX during follow-up. In all patients, the mean vitreous level of sCD163 in eyes with HRF was significantly higher than that in eyes without HRF (P = 0.036, Z=-2.093) at baseline. In the DEX group, higher sCD163 predicted greater reduction in CMT from baseline to 1 month (r = 0.470, P = 0.049). CONCLUSIONS: We found that intraoperative DEX implantation did not have beneficial effects on BCVA and CMT over a 3-month period in all patients with iERM, implying that the use of DEX for all iERM is not recommended. In contrast, for those with HRF on OCT responded better to DEX implants at the 3-month follow-up and thier vitreous fluid expressed higher levels of sCD163 at baseline. These data support the hypothesis that DEX implants may be particularly effective in treating cases where ERM is secondary to inflammation. TRIAL REGISTRATION: The trail has been registered at Chinese Clinical Trail Registry( https://www.chictr.org.cn ) on 2021/03/12 (ChiCTR2100044228). And all patients in the article were enrolled after registration.

Epidemiology and distribution of cruciate ligament injuries in children and adolescents, with an analysis of risk factors for concomitant meniscal tear.

Introduction: To investigate the epidemiological features and prevalence of cruciate ligament injuries (CLI) in children and adolescents, and to examine the potential risk factors associated with concomitant meniscal tear (MT) among this population. Methods: The demographic data and injury details of children and adolescents with CLI from Southeast China were analyzed to describe their distribution characteristics, alongside an analysis of the prevalence of MTs, the most frequent complication. In addition, binary logistic analysis was employed to ascertain the risk factors linked to MT in individuals suffering from CLI. Results: A total of 203 patients with CLI (n = 206) met the inclusion criteria, with a male-to-female ratio of 2.3:1. Notably, a higher proportion of females were aged ≤16 years old compared to males, who predominated in patients aged >16 years (P = 0.001). Among children and adolescents, anterior cruciate ligament (ACL) injuries were the primary type of CLI, accounting for 88.18% (179/203) of all cases. The majority of cases (132/203, 65.02%) were sustained during sports activities, and sprains were the predominant mechanism of injury (176/203, 86.7%). Additionally, the most common associated injury was an MT (157/203, 77.34%). The posterior horn is the most frequently affected site for both medial MT (62.93% out of 73 cases) and lateral MT (70.19% out of 73 cases). Moreover, vertical tears constituted the majority of medial MTs (59.48% out of 116 cases). Furthermore, patients with a higher BMI faced an increased risk of associated MT in comparison to non-overweight patients (88% vs. 73.86%; P = 0.038). Each increase in BMI unit was linked with a 14% higher probability of associated MT occurrence in children and adolescents with CLI (OR = 1.140; P = 0.036). Discussion: ACL injuries are a common form of knee ligament injury among children and adolescents, especially those over the age of 16, and are often the result of a sprain. Meniscal posterior horn injury is the most commonly associated injury of youth with CLI. Additionally, overweight or obese people with CLI are at a greater risk of developing MT.

A gut microbial signature for combination immune checkpoint blockade across cancer types.

Immune checkpoint blockade (ICB) targeting programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte protein 4 (CTLA-4) can induce remarkable, yet unpredictable, responses across a variety of cancers. Studies suggest that there is a relationship between a cancer patient's gut microbiota composition and clinical response to ICB; however, defining microbiome-based biomarkers that generalize across cohorts has been challenging. This may relate to previous efforts quantifying microbiota to species (or higher taxonomic rank) abundances, whereas microbial functions are often strain specific. Here, we performed deep shotgun metagenomic sequencing of baseline fecal samples from a unique, richly annotated phase 2 trial cohort of patients with diverse rare cancers treated with combination ICB (n = 106 discovery cohort). We demonstrate that strain-resolved microbial abundances improve machine learning predictions of ICB response and 12-month progression-free survival relative to models built using species-rank quantifications or comprehensive pretreatment clinical factors. Through a meta-analysis of gut metagenomes from a further six comparable studies (n = 364 validation cohort), we found cross-cancer (and cross-country) validity of strain-response signatures, but only when the training and test cohorts used concordant ICB regimens (anti-PD-1 monotherapy or combination anti-PD-1 plus anti-CTLA-4). This suggests that future development of gut microbiome diagnostics or therapeutics should be tailored according to ICB treatment regimen rather than according to cancer type.

Controlled-release hydrogel loaded with magnesium-based nanoflowers synergize immunomodulation and cartilage regeneration in tendon-bone healing.

Tendon-bone interface injuries pose a significant challenge in tissue regeneration, necessitating innovative approaches. Hydrogels with integrated supportive features and controlled release of therapeutic agents have emerged as promising candidates for the treatment of such injuries. In this study, we aimed to develop a temperature-sensitive composite hydrogel capable of providing sustained release of magnesium ions (Mg2+). We synthesized magnesium-Procyanidin coordinated metal polyphenol nanoparticles (Mg-PC) through a self-assembly process and integrated them into a two-component hydrogel. The hydrogel was composed of dopamine-modified hyaluronic acid (Dop-HA) and F127. To ensure controlled release and mitigate the "burst release" effect of Mg2+, we covalently crosslinked the Mg-PC nanoparticles through coordination bonds with the catechol moiety within the hydrogel. This crosslinking strategy extended the release window of Mg2+ concentrations for up to 56 days. The resulting hydrogel (Mg-PC@Dop-HA/F127) exhibited favorable properties, including injectability, thermosensitivity and shape adaptability, making it suitable for injection and adaptation to irregularly shaped supraspinatus implantation sites. Furthermore, the hydrogel sustained the release of Mg2+ and Procyanidins, which attracted mesenchymal stem and progenitor cells, alleviated inflammation, and promoted macrophage polarization towards the M2 phenotype. Additionally, it enhanced collagen synthesis and mineralization, facilitating the repair of the tendon-bone interface. By incorporating multilevel metal phenolic networks (MPN) to control ion release, these hybridized hydrogels can be customized for various biomedical applications.

The Anatomic and Functional Outcomes of Ozurdex-Aided Vitrectomy in Proliferative Diabetic Retinopathy.

Purpose: To investigate the 3-months outcomes of patients who underwent intraoperative intravitreal injection of Ozurdex for proliferative diabetic retinopathy (PDR). Methods: This is a prospective randomized controlled clinical trial (ChiCTR2100043399). Seventy-one patients with PDR who had indications for surgery without intravitreal injection history within 3 months preoperatively were enrolled. Patients were randomly divided into three groups based on the medicine injected intraoperatively: Ozurdex, Conbercept, and Control group. The primary outcome is the best-corrected visual acuity (BCVA) within 3 months postoperatively. The secondary outcomes include the intraocular pressure (IOP), mean sensitivity, central retinal thickness and vessels perfusion. Results: The BCVA and the mean sensitivity improved in the three groups (F = 130.8, P < 0.0001; F = 34.18, P < 0.0001), but there was no statistical difference among the three groups (F = 0.858, P = 0.552; F = 0.964, P = 0.452). The IOP was no significant differences among the three groups within 3 months postoperatively (F = 0.881, P = 0.533). Compared with the other two groups, central retinal thickness (CRT) and outer retinal layer (ORL) thickness decreased significantly in patients of the Ozurdex group (F = 3.037, P = 0.008; F = 2.626, P = 0.018), especially in the diabetic macular edema (DME) patients (F = 2.761, P = 0.0164; F = 2.572, P = 0.0240). In macular region, superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) perfusion were not shown statistical difference at 3 months postoperatively in the all three groups compared with 1 day postoperatively (P > 0.05). Conclusion: Compared with the other two groups, anatomical outcomes was improved significantly in Ozurdex group for DR patients. Ozurdex may help to improve the visual acuity and visual sensitivity, and there is no significant difference in the change of IOP and microvascular improvement. Clinical Trial Registration: This trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn, registration number ChiCTR2100043399).

Structural and interfacial properties of acetylated Millettia speciosa Champ polysaccharide and stability evaluation of the resultant O/W emulsion containing ß-carotene.

The aim of this study was to investigate the effects of acetylation modification on the structural, interfacial and emulsifying properties of Millettia speciosa Champ polysaccharide (MSCP). Besides, the influence of acetylation modification on the encapsulation properties of polysaccharide-based emulsion was also explored. Results indicated that modification resulted in a prominent reduction in molecular weight of MSCP and the interfacial layer thickness formed by acetylated MSCP (AC-MSCP) was also decreased, but the adsorption rate and ability of AC-MSCP to reduce interfacial tension were improved. AC-MSCP formulated emulsion possessed smaller droplet size (6.8 µm) and exhibited better physical stability under stressful conditions. The chemical stability of ß-carotene was also profoundly enhanced by AC-MSCP fabricated emulsion. Moreover, AC-MSCP improved lipids digestion extent, thus facilitating the formation of micelle and increasing bioaccessibility of ß-carotene. This study provided insights for rational modification of polysaccharide-based emulsifier and designing delivery system for chemically labile hydrophobic bioactive components.

Mechanically stimulated osteocytes maintain tumor dormancy in bone metastasis of non-small cell lung cancer by releasing small extracellular vesicles.

Although preclinical and clinical studies have shown that exercise can inhibit bone metastasis progression, the mechanism remains poorly understood. Here, we found that non-small cell lung cancer (NSCLC) cells adjacent to bone tissue had a much lower proliferative capacity than the surrounding tumor cells in patients and mice. Subsequently, it was demonstrated that osteocytes, sensing mechanical stimulation generated by exercise, inhibit NSCLC cell proliferation and sustain the dormancy thereof by releasing small extracellular vesicles with tumor suppressor micro-RNAs, such as miR-99b-3p. Furthermore, we evaluated the effects of mechanical loading and treadmill exercise on the bone metastasis progression of NSCLC in mice. As expected, mechanical loading of the tibia inhibited the bone metastasis progression of NSCLC. Notably, bone metastasis progression of NSCLC was inhibited by moderate exercise, and combinations with zoledronic acid had additive effects. Moreover, exercise preconditioning effectively suppressed bone metastasis progression. This study significantly advances the understanding of the mechanism underlying exercise-afforded protection against bone metastasis progression.

[Clinical Analysis of Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia in Children].

OBJECTIVE: To explore the clinical characteristics, molecular characteristics, treatment and prognosis of pediatric Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) with a therapeutic target. METHODS: A total of 27 patients of Ph-like ALL with targeted drug target were initially diagnosed in Children's Hospital of Soochow University from December 2017 to June 2021. The data of age, gender, white blood cell (WBC) count at initial diagnosis, genetic characteristics, molecular biological changes, chemotherapy regimen, different targeted drugs were given, and minimal residual disease (MRD) on day 19, MRD on day 46, whether hematopoietic stem cell transplantation (HSCT) were retrospective analyed, and the clinical characteristics and treatment effect were summarized. Survival analysis was performed by Kaplan-Meier method. RESULTS: The intensity of chemotherapy was adjusted according to the MRD level during induced remission therapy in 27 patients, 10 patients were treated with targeted drugs during treatment, and 3 patients were bridged with HSCT, 1 patient died and 2 patients survived. Among the 24 patients who did not receive HSCT, 1 patient developed relapse, and achieved complete remission (CR) after treatment with chimeric antigen receptors T cells (CAR-T). The 3-year overall survival, 3-year relapse-free survival and 3-year event-free survival rate of 27 patients were (95.5±4.4)%, (95.0±4.9)% and (90.7±6.3)% respectively. CONCLUSION: Risk stratification chemotherapy based on MRD monitoring can improve the prognosis of Ph-like ALL in children, combined with targeted drugs can achieve complete remission as soon as possible in children whose chemotherapy response is poor, and sequential CAR-T and HSCT can significantly improve the therapeutic effect of Ph-like ALL in children whose MRD is continuously positive during induced remission therapy.