Analysis of the mechanism of resistance to enzymatic hydrolysis of RS-5 resistant starch.

RS-5 refers to the resistant starch formed by complexation of starch molecules with other molecules. In this study, the molecular mechanism of RS-5 was analysed. First, it was found, when α-amylase acted on the starch-lipid complexes, the glucose residues involved in complexation cannot be hydrolyzed by α-amylase, while the glucose residues not directly involved in complexation can be hydrolyzed. Second, lipid molecules are not necessary for the formation of RS-5 and can be replaced with small peptides or decanal molecules. Considering the multiple health hazards that may result from excessive lipid intake, small peptides composed of essential amino acids may be more desirable materials for RS-5 preparation. Third, starch-lipid complexes had strong interactions with α-amylase, which provides evidence in support of the sliding continuum hydrolysis hypothesis of α-amylase. These results revealed the mechanism of RS-5 at the molecular level, which provides a reference for the production and research of RS-5.

The oxidant-antioxidant imbalance was involved in the pathogenesis of chronic rhinosinusitis with nasal polyps.

Background: Although oxidative stress is involved in the pathophysiological process of chronic rhinosinusitis with nasal polyps (CRSwNP), the specific underlying mechanism is still unclear. Whether antioxidant therapy can treat CRSwNP needs further investigation. Methods: Immunohistochemistry, immunofluorescence, western blotting and quantitative polymerase chain reaction (qPCR) analyses were performed to detect the distribution and expression of oxidants and antioxidants in nasal polyp tissues. qPCR revealed correlations between oxidase, antioxidant enzymes and inflammatory cytokine levels in CRSwNP patients. Human nasal epithelial cells (HNEpCs) and primary macrophages were cultured to track the cellular origin of oxidative stress in nasal polyps(NPs) and to determine whether crocin can reduce cellular inflammation by increasing the cellular antioxidant capacity. Results: The expression of NOS2, NOX1, HO-1 and SOD2 was increased in nasal epithelial cells and macrophages derived from nasal polyp tissue. Oxidase levels were positively correlated with those of inflammatory cytokines (IL-5 and IL-6). Conversely, the levels of antioxidant enzymes were negatively correlated with those of IL-13 and IFN-γ. Crocin inhibited M1 and M2 macrophage polarization as well as the expression of NOS2 and NOX1 and improved the antioxidant capacity of M2 macrophages. Moreover, crocin enhanced the ability of antioxidants to reduce inflammation via the KEAP1/NRF2/HO-1 pathway in HNEpCs treated with SEB or LPS. Additionally, we observed the antioxidant and anti-inflammatory effects of crocin in nasal explants. Conclusion: Oxidative stress plays an important role in the development of CRSwNP by promoting various types of inflammation. The oxidative stress of nasal polyps comes from epithelial cells and macrophages. Antioxidant therapy may be a promising strategy for treating CRSwNP.

Time-series transcriptome reveals inflammatory signature in monocytes and neutrophils following acute heat exposure in mine rescuers.

Occupational exposure to extreme high temperatures and the increasing global temperatures necessitates a deeper understanding of the impact of heat exposure on human health. However, the molecular mechanisms underlying the response of monocytes and neutrophils to heat exposure in occupational population remain to be fully elucidated. This study used longitudinal transcriptome to assess the impact of acute heat exposure (50°C for 30 min) in 10 subjects from a mine rescue team before acute heat exposure (baseline) and at 5 min, 30 min, 1 h, and 24 h after acute heat exposure (recovery). The time-series analysis revealed a coordinated molecular choreography of changes involving inflammation, coagulation, extracellular matrix, and energy metabolism. Importantly, the study characterized the inflammatory signature associated with heat exposure in monocytes and neutrophils, as evidenced by the rapid activation of the inflammation-related transcriptome following heat exposure. Additionally, we pinpointed potential regulators, such as NR4A1, FOSL1, EGR3, and ATF3. In summary, the study suggested that the initial response to heat stress in monocytes and neutrophils from mine rescue team member was primarily characterized by a pro-inflammatory stress response, which could potentially lead to the development of inflammation and ultimately result in a systemic inflammatory response in heatstroke.

Single-frequency fiber lasers based on metal thiophosphites with sub-kHz linewidths.

Metal thiophosphites (CrPX4) (X = S and Se), emerging layered metal chalcogenophosphate materials, have found extensive utility in the fields of advanced electronic devices, magnetic technologies, and electrochemical systems. However, their applications in single-frequency fiber lasers have been relatively limited. Here, liquid phase exfoliation technology is used to exfoliate the CrPX4 into few-layered samples. Subsequently, we explored the application of CrPX4-based saturable absorbers (CrPX4-SA) by precisely depositing CrPX4 nanosheets onto the surface of D-shaped fibers. This led to the successful creation of two stable single-frequency fiber lasers (SFFLs) based on CrPS4 and CrPSe4 with center wavelengths of 1550.068 nm and 1550.092 nm, respectively. The linewidth of CrPSe4 was tested and determined to be roughly 375 Hz, which is the narrowest ever value attained for an SFFL based on its structure, and its signal-to-noise ratio (SNR) was 74.17 dB. The maximum output power of each oscillator was 0.796 mW and 0.963 mW, and their corresponding power fluctuations were 2.5% and 1.4%, respectively.

2D Semi-Metallic Hafnium Ditelluride: A Novel Nonlinear Optical Material for Ultrafast and Ultranarrow Photonics Applications.

2D semi-metallic hafnium ditelluride material is used in several applications such as solar steam generation, gas sensing, and catalysis owing to its strong near-infrared absorbance, high sensitivity, and distinctive electronic structure. The zero-bandgap characteristics, along with the thermal and dynamic stability of 2D-HfTe2, make it a desirable choice for developing long-wavelength-range photonics devices. Herein, the HfTe2 -nanosheets are prepared using the liquid-phase exfoliation method, and their superior nonlinear optical properties are demonstrated by the obtained modulation depth of 11.9% (800 nm) and 6.35% (1560 nm), respectively. In addition, the observed transition from saturable to reverse saturable absorption indicates adaptability of the prepared material in nonlinear optics. By utilizing a side polished fiber-based HfTe2 -saturable absorber (SA) inside an Er-doped fiber laser cavity, a mode-locked laser with 724 fs pulse width and 56.63 dB signal-to-noise ratio (SNR) is realized for the first time. The generated laser with this SA has the second lowest mode-locking pump threshold (18.35 mW), among the other 2D material based-SAs, thus paving the way for future laser development with improved efficiency and reduced thermal impact. Finally, employing this HfTe2 -SA, a highly stable single-frequency fiber laser (SNR ≈ 74.56 dB; linewidth ≈ 1.268 kHz) is generated for the first time, indicating its promising ultranarrow photonic application.

VTe2: Broadband Saturable Absorber for Passively Q-Switched Lasers in the Near- and Mid-Infrared Regions.

In this study, we demonstrate the fabrication of a novel 2D transition metal dichalcogenide, VTe2, into a saturable absorber (SA) by using the liquid phase exfoliation method. Furthermore, the first-principles calculations were conducted to elucidate the electronic band structures and absorption spectrum. The nonlinear optical absorption properties of VTe2 at 1.0, 2.0, and 3.0 µm were measured using open-aperture Z-scan and P-scan methods, which showed saturation intensities and modulation depths of 95.57 GW/cm2 and 9.24%, 3.11 GW/cm2 and 7.26%, and 15.8 MW/cm2 and 17.1%, respectively. Furthermore, in the realm of practical implementation, the achievement of stable passively Q-switched (PQS) lasers employing SA composed of few-layered VTe2 nanosheets has manifested itself with broadband operating wavelengths from 1.0 to ∼3.0 µm. Specifically, PQS laser operations from near-infrared to mid-infrared with pulse durations of 195 and 563 ns for 1.0 and 2.0 µm solid-state lasers, respectively, and 749 ns for an Er3+-doped fluoride fiber laser at 3.0 µm were obtained. Our experimental results demonstrate that VTe2 is a potential broadband SA device for achieving PQS lasers. To the best of our knowledge, this is the first demonstration of using VTe2 as an SA in PQS lasers in the near- and mid-infrared regions, which highlights the potential of VTe2 for future research and applications in optoelectronic devices.

The attitudes of postgraduate medical students towards the curriculum by degree type: a large-scale questionnaire survey.

BACKGROUND: Chinese medical schools have offered both professional and academic degrees for postgraduate students. However, there is limited information about the attitudes of professional-degree and academic-degree students. We aimed to examine the attitudes of full-time postgraduate students towards the curriculum, stratified by degree type. METHODS: A 29-item online questionnaire was distributed to postgraduate students in West China School of Medicine of Sichuan University in 2020. The questionnaire was designed to collect students' demographic characteristics, attitudes towards curricular provision and content, and classroom organization. A comparison was made between groups based on degree type (academic degree versus professional degree). RESULTS: Overall, 645 out of 908 students at West China School of Medicine completed the questionnaire. Comparing with students pursuing academic degrees, professional-degree students were more interested if the curriculum included specialized knowledge and clinical skills, and expressed concerns over the excessive compulsory courses and inadequate optional courses (p < 0.001), particularly prominent among first-year postgraduate students. Besides, a greater proportion of professional-degree students thought the curriculum was conflict with clinical work to some extent, and they also rated taking attendance in class as less reasonable (p < 0.01). Conversely, students pursuing academic degrees expressed that the courses were inadequate in interdisciplinary curriculum and had some crossover or repetition, and they assigned a higher importance rating for the curriculum when comparing professional-degree students (all p < 0.05). CONCLUSIONS: Different attitudes toward the curriculum are observed between students pursuing professional degrees and those pursuing academic degrees. This study provides benchmark data for future postgraduate course reforms in China.

[Cost-effectiveness analysis of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in treatment of chronic rhinosinusitis].

This study aims to evaluate the effectiveness and economic efficiency of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in the treatment of chronic rhinosinusitis(CRS). The randomized controlled trial(RCT) of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in the treatment of CRS was searched against EMbase, PubMed, Cochrane Library, CNKI, VIP, SinoMed, and Wanfang. The efficacy, nasal mucociliary transport time, and safety of the therapy above in the treatment of CRS were analyzed with single-group rate and Meta-analysis, and the economy and sensitivity were evaluated from the perspective of payer. A total of 9 RCTs were included, including 1 145 patients. Meta-analysis showed that compared with Triamcinolone Acetonide Nasal Spray alone, Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in the treatment of CRS patients increased the effective rate(RR=1.17, 95%CI[1.11, 1.24], P<0.000 01) and shortened the nasal mucociliary transport time(MD=-3.32, 95%CI[-5.86,-0.78], P=0.01), there was no significant difference in the incidence of adverse reactions between the two groups. The incremental cost-effectiveness analysis showed that the treatment costs of the control group and the observation group were 44.15 yuan and 1 044.96 yuan, respectively. In the Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray treatment group, 75.48 yuan was spent to improve the effective rate of CRS by 1%. The one-way sensitivity analysis indicated the days of treatment, the RR of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray, the price of unit preparation of Biyuan Tongqiao Granules, and the effective rate of Triamcinolone Acetonide Nasal Spray alone had great influence on the incremental cost-effectiveness ratio. In conclusion, Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray improves the therapeutic effect on CRS. The probabilistic sensitivity analysis showed that when the willingness to pay was greater than 7 920 yuan(less than 0.1 of GDP per capita 8 098 yuan), the combined therapy was economically superior to the control. Due to the limited number of articles published, it is necessary to carry out a real-world clinical trial of Biyuan Tongqiao Gra-nules and Triamcinolone Acetonide Nasal Spray in the treatment of CRS, so as to compare the cost-effectiveness of Biyuan Tongqiao Granules and Triamcinolone Acetonide Nasal Spray.

Insomnia and circadian rhythm: a bibliometrics study and visualization analysis via CiteSpace.

Objective: The present study aimed to use CiteSpace to analyze the status of insomnia and circadian rhythm, identify the hot spots and trends, and provide a basis for future study. Method: The Web of Science database was searched for studies related to insomnia and circadian from its inception to 14 April 2023. CiteSpace was used to generate online maps of collaboration between countries and authors and revealed hot spots and frontiers in insomnia and circadian rhythm. Results: We searched 4,696 publications related to insomnia and circadian rhythm. Bruno Etain was the most prolific author with most publications, i.e., with 24 articles. The USA and the University of California were the leading country and the top institution in this field of study, with 1,672 and 269 articles, respectively. There was active cooperation between institutions, countries, and authors. Hot topics focused on circadian rhythm sleep disorders, circadian clock, light therapy, melatonin, and bipolar disorder. Conclusion: Based on the CiteSpace results, we recommend a more active collaboration between various countries, institutions, and authors to conduct clinical and basic research related to insomnia and circadian rhythm. Ongoing research focuses on the interaction of insomnia with circadian rhythms and the corresponding pathways of clock genes and by extension, the role of circadian rhythms in disorders such as bipolar disorder. Modulation of circadian rhythms may be a hot spot for future insomnia therapies (such as light therapy and melatonin).

Diagnosis and Therapeutic Strategies of Unusual Subglottic Pleomorphic Adenoma: A Rare Case Report and Literature Review.

Pleomorphic adenoma (PA) is primarily found in the salivary glands, and is extremely rare in the subglottic region. Here we present a subglottic PA that presented with symptoms of dry cough and dyspnea. A submucosal mass was found in the subglottic region under laryngoscopy, occluding approximately 40% of the lumen. The patient underwent the transoral endoscopic CO2 laser microsurgery under high-frequency jet ventilation for mass resection, and the pathology report supported the diagnosis of PA. At the 2-year follow-up, there was no evidence of recurrence, and the patient is currently under regular long-term monitoring. Dyspnea and dry cough are nonspecific respiratory symptoms. When no findings discovered in the regular site, it should be noted that the subglottic area is often a blind spot for both pulmonologists and otolaryngologists, and as such, requires careful examination. Transoral endoscopic CO2 laser microsurgery under high-frequency jet ventilation was found to be an effective and less invasive method for treating subglottic PA. This approach helped avoid tracheostomy and resulted in better postoperative recovery.

Curcuma Longa Induces the Transcription Factor FOXP3 to Downregulate Human Chemokine CCR5 Expression and Inhibit HIV-1 Infection.

HIV mutations occur frequently despite the substantial success of combination antiretroviral therapy, which significantly impairs HIV progression. Failure to develop specific vaccines, the occurrence of drug-resistant strains, and the high incidence of adverse effects due to combination antiviral therapy regimens call for novel and safer antivirals. Natural products are an important source of new anti-infective agents. For instance, curcumin inhibits HIV and inflammation in cell culture assays. Curcumin, the principal constituent of the dried rhizomes of Curcuma longa L. (turmeric), is known as a strong anti-oxidant and anti-inflammatory agent with different pharmacological effects. This work aims to assess curcumin's inhibitory effects on HIV in vitro and to explore the underpinning mechanism, focusing on CCR5 and the transcription factor forkhead box protein P3 (FOXP3). First, curcumin and the RT inhibitor zidovudine (AZT) were evaluated for their inhibitory properties. HIV-1 pseudovirus infectivity was determined by green fluorescence and luciferase activity measurements in HEK293T cells. AZT was used as a positive control that inhibited HIV-1 pseudoviruses dose-dependently, with IC50 values in the nanomolar range. Then, a molecular docking analysis was carried out to assess the binding affinities of curcumin for CCR5 and HIV-1 RNase H/RT. The anti-HIV activity assay showed that curcumin inhibited HIV-1 infection, and the molecular docking analysis revealed equilibrium dissociation constants of [Formula: see text]9.8[Formula: see text]kcal/mol and [Formula: see text]9.3[Formula: see text]kcal/mol between curcumin and CCR5 and HIV-1 RNase H/RT, respectively. To examine curcumin's anti-HIV effect and its mechanism in vitro, cell cytotoxicity, transcriptome sequencing, and CCR5 and FOXP3 amounts were assessed at different concentrations of curcumin. In addition, human CCR5 promoter deletion constructs and the FOXP3 expression plasmid pRP-FOXP3 (with an EGFP tag) were generated. Whether FOXP3 DNA binding to the CCR5 promoter was blunted by curcumin was examined using transfection assays employing truncated CCR5 gene promoter constructs, a luciferase reporter assay, and a chromatin immunoprecipitation (ChIP) assay. Furthermore, micromolar concentrations of curcumin inactivated the nuclear transcription factor FOXP3, which resulted in decreased expression of CCR5 in Jurkat cells. Moreover, curcumin inhibited PI3K-AKT activation and its downstream target FOXP3. These findings provide mechanistic evidence encouraging further assessment of curcumin as a dietary agent used to reduce the virulence of CCR5-tropic HIV-1. Curcumin-mediated FOXP3 degradation was also reflected in its functions, namely, CCR5 promoter transactivation and HIV-1 virion production. Furthermore, curcumin inhibition of CCR5 and HIV-1 might constitute a potential therapeutic strategy for reducing HIV progression.

Methyl vanillate for inhibiting the proliferation, migration, and epithelial-mesenchymal transition of ovarian cancer cells via the ZEB2/Snail signaling pathway.

Background: Globally, ovarian cancer is the leading cause of female reproductive-related death, with a 5-year survival rate below 50%. Conventional therapies, such as cancer cell reduction and paclitaxel chemotherapy, have strong toxicity and are prone to drug resistance. Thus, the development of alternatives for the treatment of ovarian cancer is urgently needed. Methyl vanillate is a principal component of Hovenia dulcis Thunberg. It is known that several cancer cells are inhibited by methyl vanillate; however, whether methyl vanillate can inhibit the proliferation and migration of ovarian cancer cells still needs to be further studied. Methods: In this study, cell counting kit 8 (CCK8) was used to examine the effects of methyl vanillic acid on the proliferation of SKOV3 cell lines and human ovarian surface epithelial cell (HOSEpiC) lines. Wound healing and transwell assays were used to determine the effect of methyl vanillate on cell migration. The expression of epithelial-mesenchymal transition (EMT) marker proteins (E-cadherin and vimentin), transcription factors (Snail and ZEB2), and skeletal proteins (F-actin) were evaluated with Western blotting. F-actin was detected by immunofluorescence assay. Results: The proliferation and migration of SKOV3 cells were dose-dependently inhibited by methyl vanillate, but HOSEpiC cells were not inhibited by low concentrations of methyl vanillate. Western blotting analyses revealed a significant decrease in the expression of vimentin and a significant increase in the expression of E-cadherin in SKOV3 cells treated with methyl vanillate. This finding indicated that EMT inhibition was induced by the vanillate. Furthermore, methyl vanillate inhibited the expression of transcription factors (Snail and ZEB2) in SKOV3 cells as well as cytoskeletal F-actin assembly. Conclusions: Methyl vanillate plays an important role in inhibiting EMT and cell proliferation and the migration of ovarian cancer, likely via the inhibition of the ZEB2/Snail signaling pathway. Consequently, methyl vanillate may be a promising therapeutic drug for ovarian cancer.

Comprehensive molecular and morphological analysis of Brachystemmacalycinum and Stellariaovatifolia in the tribe Alsineae (Caryophyllaceae).

Over the course of the recent decade, the composition of Alsineae has been drastically changed by means of molecular phylogeny. However, the genus Brachystemma has not been sampled in any of the previous studies, and its phylogenetic position is still pending. In addition, the related species Stellariaovatifolia, which has at times been placed in Brachystemma, Schizotechium, or Stellaria, has also not been sampled. Here, nuclear ribosomal internal transcribed spacer (ITS) and four plastid regions (trnL-F, matK, rbcL, rps16) were used to conduct phylogenetic analyses within Caryophyllaceae and the tribe Alsineae. Ancestral characters (petal margin and number of seeds) were reconstructed in the tribe Alsineae based on the phylogenetic results. Our results indicate that Brachystemma is nested in the tribe Alsineae and forms a monophylum with S.ovatifolia, and apically lobed petals and numerous seeds may be the ancestral characters in the tribe Alsineae. Based on our study, Stellariaovatifolia should be considered within Brachystemma, and Brachystemma is clearly a separate genus and now includes two species.

Why is the beautyberry so colourful? Evolution, biogeography, and diversification of fruit colours in Callicarpa (Lamiaceae).

Fruit colour is essential to seed dispersal, speciation, and biological diversity in global ecosystems. The relationship between fruit-colour variation and species diversification has long been of interest in evolutionary biology, but remains poorly understood at the genus level. Here, we used Callicarpa, a typical representative of pantropical angiosperm, to analyse whether fruit colours are correlated with biogeographic distribution, dispersal events, and diversification rate. We estimated a time-calibrated phylogeny for Callicarpa and reconstructed ancestral fruit colour. Utilizing phylogenetic methods, we estimated the major dispersal events across the phylogenetic tree and the most likely fruit colours related to each dispersal event, and tested whether the dispersal frequencies and distances of the four fruit colours between major biogeographical areas were equal. We then tested whether fruit colours are correlated with latitude, elevation, and diversification rate. Biogeographical reconstructions showed that Callicarpa originated in the East Asia and Southeast Asia during the Eocene (∼35.53 Ma) and diverse species diverged mainly in the Miocene and lasted into the Pleistocene. Large-scale dispersal events were significantly associated with violet-fruited lineages. Furthermore, different fruit colours were markedly correlated with different latitudes and elevations (e.g., violet fruits were correlated with higher latitudes and elevations; red fruits and black fruits with lower latitudes; white fruits with higher elevations). Notably, violet fruits were statistically associated with highest diversification rates, driving fruit colour variation among different regions globally. Our results contribute to further understanding why fruit colour is so variable at the genus level of angiosperms in different areas around the world.

CrPS4 Nanoflakes as Stable Direct-Band-Gap 2D Materials for Ultrafast Pulse Laser Applications.

Two-dimensional (2D) materials have attracted considerable attention due to their potential for generating ultrafast pulsed lasers. Unfortunately, the poor stability of most layered 2D materials under air exposure leads to increased fabrication costs; this has limited their development for practical applications. In this paper, we describe the successful preparation of a novel, air-stable, and broadband saturable absorber (SA), the metal thiophosphate CrPS4, using a simple and cost-effective liquid exfoliation method. The van der Waals crystal structure of CrPS4 consists of chains of CrS6 units interconnected by phosphorus. In this study, we calculated the electronic band structures of CrPS4, revealing a direct band gap. The nonlinear saturable absorption properties, which were investigated using the P-scan technique at 1550 nm, revealed that CrPS4-SA had a modulation depth of 12.2% and a saturation intensity of 463 MW/cm2. Integration of the CrPS4-SA into Yb-doped fiber and Er-doped fiber laser cavities led to mode-locking for the first time, resulting in the shortest pulse durations of 298 ps and 500 fs at 1 and 1.5 µm, respectively. These results indicate that CrPS4 has great potential for broadband ultrafast photonic applications and could be developed into an excellent candidate for SA devices, providing new directions in the search for stable SA materials and for their design.

Advantageous Strain Sensing Performances of FBG Strain Sensors Equipped with Planar UV-Curable Resin.

The existing optical strain sensors based on fiber Bragg grating (FBG) have limitations, such as a complex structure, a limited strain range (±200 µÎµ) and poor linearity performance (R-squared value < 0.9920); these limitations affect their potential practical applications. Here, four FBG strain sensors equipped with planar UV-curable resin are investigated. The proposed FBG strain sensors have a simple structure, a large strain range (±1800 µÎµ) and excellent linearity performance (R-squared value ≥ 0.9998); they further produce the following performances: (1) good optical properties, including an undistorted Bragg peak shape, narrow bandwidth (-3 dB bandwidth ≤ 0.65 nm) and a high side mode suppression ratio (SMSR, the absolute value of SMSR ≥ 15 dB); (2) good temperature sensing properties with high temperature sensitivities (≥47.7 pm/°C) and a good linearity performance (R-squared value ≥ 0.9990); and (3) excellent strain sensing properties with no hysteresis behavior (hysteresis error ≤ 0.058%) and excellent repeatability (repeatability error ≤ 0.045%). Based on their excellent properties, the proposed FBG strain sensors are expected to be applied as high-performance strain sensing devices.

scRNA-seq reveals aging-related immune cell types and regulators in vaginal wall from elderly women with pelvic organ prolapse.

Introduction: In the pathology of pelvic organ prolapse (POP), little is known about the contributing role of pelvic microenvironment. Also, the age-related differences in pelvic microenvironment of POP patients is always ignored. In the present study, we investigated the age-related differences in pelvic microenvironment between Young POP patients and Old POP patients, and the novel cell types and critical regulators which contributes to the age-related differences. Methods: Single-cell transcriptomic analyses were used to detect the changes in cell composition and gene expression from the pelvic microenvironment of control group (<60 years), Young POP group (<60 years) and Old POP group (>60 years). Then, immunohistochemistry and immunofluorescence were used to verify the novel cell types and critical regulators in the pelvic microenvironment. Furthermore, histopathological alteration and mechanical property alteration in POP with different ages were revealed by vaginal tissue histology and biomechanical testing. Results: The up-regulated biological process in Old women with POP is mainly related to chronic inflammation, while the up-regulated biological process in Young women with POP is mainly related to extracellular matrix metabolism. Meantime, CSF3+ endothelial cells and FOLR2+ macrophages were found to play a central role in inducing pelvic chronic inflammation. Furthermore, the collagen fiber and mechanical property of POP patients decreased with aging. Conclusions: Taken together, this work provides a valuable resource for deciphering the aging-related immune cell types and the critical regulators in pelvic microenvironment. With better understanding of normal and abnormal events in this pelvic microenvironment, we provided rationales of personalized medicine for POP patients with different ages.

Chlorogenic acid delays the progression of Parkinson's disease via autophagy induction in Caenorhabditis elegans.

OBJECTIVES: Parkinson's disease (PD) is the second most common neurodegenerative disease. Chlorogenic acid (CGA) is a polyphenolic substance derived from various medicinal plants. Although CGA is reported to have potential anti-PD effect, the beneficial effect and the underlying mechanism remain unclear. In this study, we aimed to further investigate the protective effect and clarify the mechanism of action of CGA in Caenorhabditis elegans (C. elegans) models of PD. METHODS: Measurements of a-synuclein aggregation, movement disorders, and lipid, ROS and malondialdehyde (MDA) contents were observed in NL5901 nematodes. Determinations of dopamine (DA) neuron degeneration, food perception, and ROS content were performed in 6-OHDA-exposed BZ555 nematodes. The autophagy activation of CGA was monitored using DA2123 and BC12921 nematodes. Meanwhile, RNAi technology was employed to knockdown the autophagy-related genes and investigate whether the anti-PD effect of CGA was associated with autophagy induction in C. elegans. RESULTS: CGA significantly reduced α-synuclein aggregation, improved motor disorders, restored lipid content, and decreased ROS and MDA contents in NL5901 nematodes. Meanwhile, CGA inhibited DA neuron-degeneration and improved food-sensing behavior in 6-OHDA-exposed BZ555 nematodes. In addition, CGA increased the number of GFP::LGG-1 foci in DA2123 nematodes and degraded p62 protein in BC12921 nematodes. Meanwhile, CGA up-regulated the expression of autophagy-related genes in NL5901 nematodes. Moreover, the anti-PD effect of CGA was closely related to autophagy induction via increasing the expression of autophagy-related genes, including unc-51, bec-1, vps-34, and lgg-1. CONCLUSIONS: The present study indicates that CGA exerts neuroprotective effect in C. elegans via autophagy induction.

Cost-effectiveness analysis of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in treatment of chronic rhinosinusitis / 中国中药杂志

This study aims to evaluate the effectiveness and economic efficiency of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in the treatment of chronic rhinosinusitis(CRS). The randomized controlled trial(RCT) of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in the treatment of CRS was searched against EMbase, PubMed, Cochrane Library, CNKI, VIP, SinoMed, and Wanfang. The efficacy, nasal mucociliary transport time, and safety of the therapy above in the treatment of CRS were analyzed with single-group rate and Meta-analysis, and the economy and sensitivity were evaluated from the perspective of payer. A total of 9 RCTs were included, including 1 145 patients. Meta-analysis showed that compared with Triamcinolone Acetonide Nasal Spray alone, Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray in the treatment of CRS patients increased the effective rate(RR=1.17, 95%CI[1.11, 1.24], P<0.000 01) and shortened the nasal mucociliary transport time(MD=-3.32, 95%CI[-5.86,-0.78], P=0.01), there was no significant difference in the incidence of adverse reactions between the two groups. The incremental cost-effectiveness analysis showed that the treatment costs of the control group and the observation group were 44.15 yuan and 1 044.96 yuan, respectively. In the Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray treatment group, 75.48 yuan was spent to improve the effective rate of CRS by 1%. The one-way sensitivity analysis indicated the days of treatment, the RR of Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray, the price of unit preparation of Biyuan Tongqiao Granules, and the effective rate of Triamcinolone Acetonide Nasal Spray alone had great influence on the incremental cost-effectiveness ratio. In conclusion, Biyuan Tongqiao Granules combined with Triamcinolone Acetonide Nasal Spray improves the therapeutic effect on CRS. The probabilistic sensitivity analysis showed that when the willingness to pay was greater than 7 920 yuan(less than 0.1 of GDP per capita 8 098 yuan), the combined therapy was economically superior to the control. Due to the limited number of articles published, it is necessary to carry out a real-world clinical trial of Biyuan Tongqiao Gra-nules and Triamcinolone Acetonide Nasal Spray in the treatment of CRS, so as to compare the cost-effectiveness of Biyuan Tongqiao Granules and Triamcinolone Acetonide Nasal Spray.