Correction: Kirigami-enabled stretchable laser-induced graphene heaters for wearable thermotherapy.

Correction for 'Kirigami-enabled stretchable laser-induced graphene heaters for wearable thermotherapy' by Junyu Chen et al., Mater. Horiz., 2024, 11, 2010-2020, https://doi.org/10.1039/D3MH01884A.

Kirigami-enabled stretchable laser-induced graphene heaters for wearable thermotherapy.

Flexible and stretchable heaters are increasingly recognized for their great potential in wearable thermotherapy to treat muscle spasms, joint injuries and arthritis. However, issues like lengthy processing, high fabrication cost, and toxic chemical involvement are obstacles on the way to popularize stretchable heaters for medical use. Herein, using a single-step customizable laser fabrication method, we put forward the design of cost-effective wearable laser-induced graphene (LIG) heaters with kirigami patterns, which offer multimodal stretchability and conformal fit to the skin around the human body. First, we develop the manufacturing process of the LIG heaters with three different kirigami patterns enabling reliable stretchability by out-of-plane buckling. Then, by adjusting the laser parameters, we confirm that the LIG produced by medium laser power could maintain a balance between mechanical strength and electrical conductivity. By optimizing cutting-spacing ratios through experimental measurements of stress, resistance and temperature profiles, as well as finite element analysis (FEA), we determine that a larger cutting-spacing ratio within the machining precision will lead to better mechanical, electrical and heating performance. The optimized stretchable heater in this paper could bear significant unidirectional strain over 100% or multidirectional strain over 20% without major loss in conductivity and heating performance. On-body tests and fatigue tests also proved great robustness in practical scenarios. With the advantage of safe usage, simple and customizable fabrication, easy bonding with skin, and multidirectional stretchability, the on-skin heaters are promising to substitute the traditional heating packs/wraps for thermotherapy.

Proton pump inhibitors induced fungal dysbiosis in patients with gastroesophageal reflux disease.

Gut mycobiota inhabits human gastrointestinal lumen and plays a role in human health and disease. We investigated the influence of proton pump inhibitors (PPIs) on gastric mucosal and fecal mycobiota in patients with gastroesophageal reflux diseases (GERD) by using Internal Transcribed Spacer 1 sequencing. A total of 65 participants were included, consisting of the healthy control (HC) group, GERD patients who did not use PPIs (nt-GERD), and GERD patients who used PPIs, which were further divided into short-term (s-PPI) and long-term PPI user (l-PPI) groups based on the duration of PPI use. The alpha diversity and beta diversity of gastric mucosal mycobiota in GERD patients with PPI use were significantly different from HCs, but there were no differences between s-PPI and l-PPI groups. LEfSe analysis identified Candida at the genus level as a biomarker for the s-PPI group when compared to the nt-GERD group. Meanwhile, Candida, Nothojafnea, Rhizodermea, Ambispora, and Saccharicola were more abundant in the l-PPI group than in the nt-GERD group. Furthermore, colonization of Candida in gastric mucosa was significantly increased after PPI treatment. However, there was no significant difference in Candida colonization between patients with endoscopic esophageal mucosal breaks and those without. There were significant differences in the fecal mycobiota composition between HCs and GERD patients regardless whether or not they used PPI. As compared to nt-GERD patient samples, there was a high abundance of Alternaria, Aspergillus, Mycenella, Exserohilum, and Clitopilus in the s-PPI group. In addition, there was a significantly higher abundance of Alternaria, Aspergillus, Podospora, Phallus, and Monographella in the l-PPI group than nt-GERD patients. In conclusion, our study indicates that dysbiosis of mycobiota was presented in GERD patients in both gastric mucosal and fecal mycobiota. PPI treatment may increase the colonization of Candida in the gastric mucosa in GERD patients.

Long-Term Tillage and Crop Rotation Regimes Reshape Soil-Borne Oomycete Communities in Soybean, Corn, and Wheat Production Systems.

Soil-borne oomycetes include devastating plant pathogens that cause substantial losses in the agricultural sector. To better manage this important group of pathogens, it is critical to understand how they respond to common agricultural practices, such as tillage and crop rotation. Here, a long-term field experiment was established using a split-plot design with tillage as the main plot factor (conventional tillage (CT) vs. no till (NT), two levels) and rotation as the subplot factor (monocultures of soybean, corn, or wheat, and corn-soybean-wheat rotation, four levels). Post-harvest soil oomycete communities were characterized over three consecutive years (2016-2018) by metabarcoding the Internal Transcribed Spacer 1 (ITS1) region. The community contained 292 amplicon sequence variants (ASVs) and was dominated by Globisporangium spp. (85.1% in abundance, 203 ASV) and Pythium spp. (10.4%, 51 ASV). NT decreased diversity and community compositional structure heterogeneity, while crop rotation only affected the community structure under CT. The interaction effects of tillage and rotation on most oomycetes species accentuated the complexity of managing these pathogens. Soil and crop health represented by soybean seedling vitality was lowest in soils under CT cultivating soybean or corn, while the grain yield of the three crops responded differently to tillage and crop rotation regimes.

LRP1B mutation is associated with tumor immune microenvironment and progression-free survival in lung adenocarcinoma treated with immune checkpoint inhibitors.

Background: Only a fraction of lung adenocarcinoma (LUAD) patients are eligible for immunotherapy. The identification of biomarkers for immunotherapy is crucial to improve patient outcomes. This study aims to systemically analyze LRP1B mutation and its association with the tumor immune microenvironment (TIME) and immunotherapy. Methods: A cohort of immune checkpoint inhibitors (ICIs)-treated LUAD patients was analyzed to assess the association of LRP1B mutation with immunotherapy prognosis. Another cohort of LUAD patients with genetic and transcriptomic data was also obtained from The Cancer Genome Atlas (TCGA). By investigating the ICIs and the TCGA-LUAD cohorts, we compared the differences in mutation profiles, immunogenicity, TIME, and DNA damage repair (DDR) mutations between the LRP1B-mutated and LRP1B wild-type groups. Additionally, we performed multiplex immunohistochemistry (mIHC) to validate the differences in the tumor microenvironment. Results: Our results revealed that LRP1B mutation is associated with multiple immune-related pathways. Analysis of TIME indicated that LUAD patients with LRP1B mutation expressed significant levels of genes involved in antigen presentation, cytotoxicity, chemokines, and pro-inflammatory mediators, whereas a few immune checkpoint genes were highly expressed in the LRP1B-mutated group as well. Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) analysis indicated that LRP1B-mutated LUAD patients had higher infiltration of active immune cells. Multiplex IHC analysis showed that LRP1B-mutated LUAD patients had elevated programmed death ligand-1 (PD-L1) expression and immune cell infiltration. Patients with LRP1B mutation had higher tumor mutation burden, neoantigens, as well as more mutated genes in the DDR-related pathways. Finally, LRP1B-mutated LUAD patients showed a significant prolongation of progression-free survival (PFS) in the ICIs cohort and could be effectively predicted by our constructed nomogram. Conclusions: Our study suggests that LRP1B mutation is associated with higher immune cell infiltration and elevated immune gene expression in TIME and potentially serves as a prognostic biomarker for LUAD patients treated with ICIs.

Value of diffusion-weighted imaging in diagnosis and therapy response assessment of hepatic fungal infection in patients with acute leukemia.

OBJECTIVE: To investigate the role of diffusion-weighted imaging (DWI) for diagnosis and posttreatment assessment of hepatic fungal infection in patients with acute leukemia. METHODS: Patients with acute leukemia and highly suspected hepatic fungal infection were collected in the study. All the patients underwent MRI examination, including initial and follow-up DWI. The apparent diffusion coefficient (ADC) values of the lesions and the normal liver parenchyma were compared using Student's t-test. The ADC values of the hepatic fungal lesions of pretreatment and posttreatment were compared using paired t-test. RESULTS: A total of 13 patients with hepatic fungal infections have enrolled this study. Hepatic lesions were rounded or oval shaped, measured from 0.3 to 3 cm in diameter. The lesions showed significantly hyperintense signal on DWI and markedly hypointense signal on the ADC map, reflecting a marked restricted diffusion. The mean ADC values of the lesions were significantly lower than those of normal liver parenchyma (1.08 ± 0.34 × 10-3 vs. 1.98 ± 0.12 × 10-3 mm2 /s, p < 0.001). After treatment, the mean ADC values of the lesions were significantly increased when comparing with those of pretreatment (1.39 ± 0.29 × 10-3 vs. 1.06 ± 0.10 × 10-3 mm2 /s, p = .016). CONCLUSION: DWI can provide diffusion information of hepatic fungal infection in patients with acute leukemia, which could be taken as a valuable tool for diagnosis and therapy response assessment of these patients.

Core and conditionally rare taxa as indicators of agricultural drainage ditch and stream health and function.

BACKGROUND: The freshwater microbiome regulates aquatic ecological functionality, nutrient cycling, pathogenicity, and has the capacity to dissipate and regulate pollutants. Agricultural drainage ditches are ubiquitous in regions where field drainage is necessary for crop productivity, and as such, are first-line receptors of agricultural drainage and runoff. How bacterial communities in these systems respond to environmental and anthropogenic stressors are not well understood. In this study, we carried out a three year study in an agriculturally dominated river basin in eastern Ontario, Canada to explore the spatial and temporal dynamics of the core and conditionally rare taxa (CRT) of the instream bacterial communities using a 16S rRNA gene amplicon sequencing approach. Water samples were collected from nine stream and drainage ditch sites that represented the influence of a range of upstream land uses. RESULTS: The cross-site core and CRT accounted for 5.6% of the total number of amplicon sequence variants (ASVs), yet represented, on average, over 60% of the heterogeneity of the overall bacterial community; hence, well reflected the spatial and temporal microbial dynamics in the water courses. The contribution of core microbiome to the overall community heterogeneity represented the community stability across all sampling sites. CRT was primarily composed of functional taxa involved in nitrogen (N) cycling and was linked to nutrient loading, water levels, and flow, particularly in the smaller agricultural drainage ditches. Both the core and the CRT were sensitive responders to changes in hydrological conditions. CONCLUSIONS: We demonstrate that core and CRT can be considered as holistic tools to explore the temporal and spatial variations of the aquatic microbial community and can be used as sensitive indicators of the health and function of agriculturally dominated water courses. This approach also reduces computational complexity in relation to analyzing the entire microbial community for such purposes.

Efficacy of endoscopic anterior fundoplication with a novel ultrasonic surgical endostapler for gastroesophageal reflux disease: Six-month results from a multicenter prospective trial.

Background and Objectives: Endoscopic therapy is an option for the treatment of refractory gastroesophageal reflux disease (GERD). We aimed to evaluate the efficacy and safety of transoral incisionless fundoplication with the Medigus ultrasonic surgical endostapler (MUSE™) for refractory GERD. Materials and Methods: Patients with 2 years of documented GERD symptoms and at least 6 months of proton-pump inhibitors (PPIs) therapy were enrolled in four medical centers from March 2017 to March 2019. The GERD health-related quality of life (HRQL) score, GERD questionnaire score, total acid exposure on esophageal pH probe monitoring, the gastroesophageal flap valve (GEFV), esophageal manometry, and PPIs dosage were compared between the pre- and post-MUSE procedure. All of the side effects were recorded. Results: A reduction of at least 50% in the GERD-HRQL score was observed in 77.8% (42/54) patients. Most patients 74.1% (40/54) discontinued PPIs and 11.1% (6/54) reported a ≥50% dose reduction. The percentage of patients who had normalized acid exposure time after the procedure was 46.9% (23/49). The existence of hiatal hernia at baseline was negatively correlated with the curative effect. Mild pain was common and resolved within 48 h postprocedure. Serious complications were pneumoperitoneum (one case), mediastinal emphysema combined with pleural effusion (two cases). Conclusions: Endoscopic anterior fundoplication with MUSE was an effective treatment for refractory GERD, but still needs refinement and improvement in safety aspect. Esophageal hiatal hernia may affect the efficacy of MUSE. (www.chictr.org.cn, ChiCTR2000034350).

Hyperbaric Oxygen Therapy Ameliorates Sperm Parameters in Apolipoprotein E Knockout Mice Testes by Attenuating Oxidative Stress and Inflammation.

Apolipoprotein E (ApoE) is a member of apolipoprotein (apo) family and plays critical role in lipid metabolism. In this study, the relationship between abnormal lipid metabolism caused by ApoE-deficient and male reproduction was investigated. The effect of hyperbaric oxygen (HBO) therapy on 7-month-old ApoE-knockout male mice was assessed subsequently. Mice were randomly divided into 3 groups: control group (WT), ApoE (- / -) group (AP-CON), and ApoE (- / -) plus HBO group (AP-HBO), which received HBO treatment. We found that ApoE knockout caused a decrease in male reproductive capacity due to the reduced total sperm motility, progressive motility (PR), and lower blastocyst formation rate. HBO treatment could accelerate serum lipoprotein metabolism including LDL, T-CHO, and TG and semen quality. As a result, fertilization and blastocyst formation of AP-HBO group were higher than that of AP-CON, proving positive therapeutic effect. Mechanism exploration found that HBO treatment ameliorated the testicular microenvironment by attenuating inflammatory factor production and oxidative stress, eventually improved the sperm motility. Collectively, our study provided more evidences of HBO treatment for improving the semen quality of patients with abnormal lipid metabolism caused by ApoE-deficient.

Selection of oat (Avena sativa L.) drought-tolerant genotypes based on multiple yield-associated traits.

BACKGROUND: Most plant breeding and agricultural practices are based on selecting genotypes for yield. However, this is inadequate to screen crop varieties for specific attributes, such as drought tolerance. In this study, we quantified the response of oat (Avena sativa L.) plant physiological and morphological traits to drought stress and selected some key traits to establish a genotype by yield*trait (GYT)-based method for ranking 30 oat genotypes. The effectiveness of this method was also evaluated under drought conditions. RESULTS: Water-deficit treatment significantly reduced leaf chlorophyll, root morphological traits, groat yield and associated components, such as mean grain weight. We observed that the genotypes 'JUSTICE' and 'BOLINA' had the smallest and largest yield loss, respectively, after exposure to drought stress, but showed opposite trends in the biomass allocation of roots and grains. This indicated that drought tolerance was highly dependent on the distribution of photoassimilates. Our results also illustrated that the GYT method is a trade-off approach and more effective in selecting oat ideotypes under drought conditions than the yield-related index method because it combines yield, yield stability, and related agronomic traits in the calculation process. CONCLUSION: Drought-tolerant genotypes had more biomass allocated to roots and grains with higher chlorophyll content and better root structure, e.g. longer root lengths than drought-sensitive lines. By integrating yield and yield-related traits, the GYT approach is more practical than traditional single-trait selection methods when assessing drought tolerance. © 2023 His Majesty the King in Right of Canada. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. Reproduced with the permission of the Minister of Agriculture and Agri-Food Canada.

Hyperbaric Oxygen Treatment Ameliorates the Decline in Oocyte Quality and Improves the Fertility of Aged Female Mice.

The age-related decay in oocyte quality contributes to the gradual decline in fertility and the final occurrence of natural sterility. In this study, we aimed to investigate the effects of the hyperbaric oxygen treatment (HBOT) on oocyte quality in aging mouse oocyte. Eight- and forty-week-old female C57BL/6 J mice were treated with HBO for 10 days, and the quality of oocytes was analyzed. The results revealed that HBOT improved the age-related serum AMH levels. While compared with untreated aged mice, HBOT showed reduced follicular apoptosis and improved oocyte maturation, fertilization, and blastocyst formation in aged mice. HBO triggered changes in the microRNA expression in the ovaries of aged mice. In this study, 27 DEGs were identified in the HBOT mouse ovarian tissues, of which 9 were upregulated and 18 were downregulated. Notably, KEGG analysis revealed that these genes involved in different biological processes differed significantly in the ovary. Among these, the PI3K-Akt signaling was the most prominent pathway that controlled the recruitment and growth of primordial follicles. The calcium signaling pathway was found to be involved during the peri-implantation period. These results suggest that HBOT can be applied to improve the quality of oocytes, and it could be a potential clinical application to improve the fertility of aged female.

[The role of the ubiquitin proteasome system and PP2A in spermatogenesis].

The ubiquitin proteasome system (UPS) plays an important role in cell degradation, and is involved in many biological processes such as cell cycle regulation, immune response, DNA damage repair, and signal transduction. It also acts a crucial part in spermatogenesis by selectively degrading proteins and regulating such processes as DNA repair and protamine histone replacement. PP2A, as an essential serine/threonine phosphatase, participates in a variety of life activities. Studies have shown the involvement of UPS in the ubiquitination regulation of PP2A and that of PP2A in several stages of meiosis. This review updates the roles of UPS and PP2A in spermatogenesis.

Catalytic Subunit of Protein Phosphatase 2A (PP2Ac) Influences the Meiosis Initiation During Spermatocyte Meiosis Prophase I.

As a serine/threonine phosphatase, protein phosphatase 2A (PP2A) is essential in numerous physiological processes. By generating a catalytic subunit of PP2A (Ppp2ca) conditional knockout (CKO) in C57BL/6 J mice, we explored the possible mechanisms of azoospermia by focusing on meiosis initiation and spermatogenesis. The deficiency of Ppp2ca in germ cells conspicuously disturbed spermatogonial differentiation and led to pachynema arrest, accompanied by significant apoptosis in germ cells and defects in programmed double-strand break (DSB) repair. While the formation of XY body was normal, respectively. Ppp2ca-deficient spermatocytes exhibited an abnormal cohesion complex degradation of chromosome, probably contributing to cell death. Furthermore, transcriptomics analysis was conducted to prove several genes involved in spermatogenesis and exhibited transcriptional dysregulations in Ppp2ca-deficient testes. Our study demonstrates the irreplaceable role of PP2A in spermatogenesis and provides more evidences of azoospermia etiology.

Removal of triclosan from water by sepiolite supported bimetallic Fe/Ni nanoparticles.

A simple and low-cost route to fabricate sepiolite-supported bimetallic Fe/Ni (Sep-Fe/Ni) nanoparticles was obtained by synchronous liquid phase reduction method. The as prepared composite was used to remove triclosan (TCS) from aqueous solutions. X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and Brunauer-Emmett-Teller (BET) analysis were used for characterization of the materials. As the supporting material, Sep dispersed Fe/Ni nanoparticles on its surface effectively and reduced the agglomeration phenomenon, providing more reactive sites. Sep-Fe/Ni had a large surface area of 90.5 m2/g, which was considerably higher than that of Fe/Ni (9.2 m2/g). Sep-Fe/Ni exhibited an enhanced TCS removal efficiency, as compared to the Fe/Ni and Sep materials. Operation factors, including the solution pH, initial TCS concentration, and material dosage, were investigated and found to be influential for TCS removal. The kinetic analysis indicated that the depletion of TCS in aqueous solutions conformed to the pseudo-first-order kinetic model under optimized conditions. The transformation pathway of TCS was studied in detail, revealing that the dechlorination of TCS by Sep-Fe/Ni is a stepwise reaction, namely from TCS to di-chlorinated intermediates, with the newly formed intermediate products also degrading into mono-chlorinated products by further reductive dechlorination. This study demonstrated that Sep-Fe/Ni is a promising reductant for TCS removal in water.

Long-Term Efficacy of Low-Intensity Single Donor Fecal Microbiota Transplantation in Ulcerative Colitis and Outcome-Specific Gut Bacteria.

Aims: To assess the long-term efficacy and safety of single-donor, low-intensity fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), and to identify the outcome-specific gut bacteria. Design: Thirty-one patients with active UC (Mayo scores ≥ 3) were recruited, and all received FMT twice, at the start of the study and 2∼3 months later, respectively, with a single donor and a long-term follow-up. The fecal microbiome profile was accessed via 16S rRNA sequencing before and after FMT. Results: After the first FMT, 22.58% (7/31) of patients achieved clinical remission and endoscopy remission, with the clinical response rate of 67.74% (21/31), which increased to 55% (11/20) and 80% (16/20), respectively, after the second FMT. No serious adverse events occurred in all patients. During 4 years of follow-up, the mean remission period of patients was 26.5 ± 19.98 m; the relapse rate in the 12 remission patients was 33.33% within 1 year, and 58.3% within 4 years. At baseline, UC patients showed an enrichment in some proinflammatory microorganisms compared to the donor, such as Bacteroides fragilis, Clostridium difficile, and Ruminococcus gnavus, and showed reduced amounts of short-chain fatty acid (SCFA) producing bacteria especially Faecalibacterium prausnitzii. FMT induced taxonomic compositional changes in the recipient gut microbiota, resulting in a donor-like state. Given this specific donor, UC recipients with different outcomes showed distinct gut microbial features before and after FMT. In prior to FMT, relapse was characterized by higher abundances of Bacteroides fragilis and Lachnospiraceae incertae sedis, together with lower abundances of Bacteroides massiliensis, Roseburia, and Ruminococcus; Prevotella copri was more abundant in the non-responders (NR); and the patients with sustained remission (SR) had a higher abundance of Bifidobacterium breve. After FMT, the NR patients had a lower level of Bifidobacterium compared to those with relapse (Rel) and SR, while a higher level of Bacteroides spp. was observed in the Rel group. Conclusion: Low-intensity single donor FMT could induce long remission in active UC. The gut microbiota composition in UC patients at baseline may be predictive of therapeutic response to FMT.

Kirigami-inspired stents for sustained local delivery of therapeutics.

Implantable drug depots have the capacity to locally meet therapeutic requirements by maximizing local drug efficacy and minimizing potential systemic side effects. Tubular organs including the gastrointestinal tract, respiratory tract and vasculature all manifest with endoluminal disease. The anatomic distribution of localized drug delivery for these organs using existing therapeutic modalities is limited. Application of local depots in a circumferential and extended longitudinal fashion could transform our capacity to offer effective treatment across a range of conditions. Here we report the development and application of a kirigami-based stent platform to achieve this. The stents comprise a stretchable snake-skin-inspired kirigami shell integrated with a fluidically driven linear soft actuator. They have the capacity to deposit drug depots circumferentially and longitudinally in the tubular mucosa of the gastrointestinal tract across millimetre to multi-centimetre length scales, as well as in the vasculature and large airways. We characterize the mechanics of kirigami stents for injection, and their capacity to engage tissue in a controlled manner and deposit degradable microparticles loaded with therapeutics by evaluating these systems ex vivo and in vivo in swine. We anticipate such systems could be applied for a range of endoluminal diseases by simplifying dosing regimens while maximizing drug on-target effects through the sustained release of therapeutics and minimizing systemic side effects.

MicroRNA­378d inhibits Glut4 by targeting Rsbn1 in vitamin D deficient ovarian granulosa cells.

Vitamin D (VD) is not only associated with bone growth and development, but is also closely associated with numerous other pathological conditions. The present study aimed to investigate the effect of microRNA (miRNA/miR)­378d on ovarian granulosa cells by regulating the round spermatid basic protein 1 (Rsbn1) in the absence of VD. The abnormal expression of miRNAs in ovarian tissues of the VD­deficient mouse was analyzed using transcriptome sequencing. miR­378d, glucose transporter 4 (Glut4) and aromatase (Cyp19a) expression levels were examined via reverse transcription­quantitative (RT­q)PCR and western blotting. The expression levels of Rsbn1, Glut4 and Cyp19a were detected in transfected mouse ovarian granulosa cells. The targeting regulation between miR­378d and Rsbn1 was verified using double reporter gene assay and functional rescue experiments. Among the 672 miRNAs that were differentially expressed, cluster analysis revealed that 17 were significantly upregulated and 16 were significantly downregulated. Moreover, miR­378d showed significant upregulation, which was further verified via RT­qPCR. It was identified that the protein expression level of Rsbn1 was significantly downregulated. Furthermore, Glut4 mRNA expression was significantly decreased in the mimic group but markedly increased in the inhibitor group. By contrast, the mRNA expression levels of Rsbn1 and Cyp19a did not demonstrate any significant difference. The western blotting results indicated that the protein expression levels of Rsbn1 and Glut4 were decreased and increased, respectively, while Cyp19a did not show any significant change. In addition, the double reporter gene experiments confirmed that Rsbn1 was the target gene of miR­378d. Collectively, the present results demonstrated that miR­378d was abnormally overexpressed in the ovarian tissues of the VD­deficient mice, and that miR­378d could inhibit Glut4 production by targeting Rsbn1, which may lead to insulin resistance.

Vitamin D deficiency inhibits microRNA-196b-5p which regulates ovarian granulosa cell hormone synthesis, proliferation, and apoptosis by targeting RDX and LRRC17.

BACKGROUND: In polycystic ovary syndrome (PCOS), ovarian physiology is tightly linked to the metabolic disturbances observed in this disease. Vitamin D (VD) plays an important role in the regulation of ovulatory dysfunction and can influence genes involved in steroidogenesis in granulosa cells (GCs). However, its role in the proliferation and apoptosis of ovarian GCs is unclear. The present study aimed to investigate the role of microRNA-196-5p (miR-196b-5p) in the hormone synthesis, proliferation, and apoptosis of ovarian GCs. METHODS: The abnormal expression of miRNAs in ovarian tissues of VD-deficient mice was analyzed using transcriptome sequencing. The direct target of miR-196b-5p was predict and confirmed by bioinformatics analysis and the dual-luciferase reporter assay. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect the levels of miR-196b-5p, cell proliferation was detected via the CCK8 assay, and cell apoptosis and reactive oxygen species (ROS) were measured via flow cytometry. The levels of radixin (RDX), leucine rich repeat containing 17 (LRRC17), aromatase (CYP19A1), and glucose transporter 4 (GLUT4) were detected by performing RT-qPCR or western blot. RESULTS: We found that miR-196b-5p was significantly downregulated among the 672 miRNAs that were differentially expressed (DE) in VD-deficient mice. In addition, the results demonstrated that downregulated expression of miR-196b-5p significantly increased the level of RDX and LRRC17, and reduced expression of miR-196b-5p significantly promoted ovarian GC apoptosis and inhibited cell proliferation. Downregulated expression of miR-196b-5p promoted cellular ROS production and inhibited sex hormone production and glucose uptake. Transfection with miR-196b-5p mimics significantly increased the expression of CYP19A1 and GLUT4 and decreased the RDX and LRRC17 levels in ovarian GCs. CONCLUSIONS: This study shows that miR-196b-5p can regulate the oxidative stress (OS), glucose uptake, and steroid production pathway of GCs, thus promoting follicular development and maturation. This is a step towards a feasible treatment for PCOS.

[Biosafety in andrology laboratories during the outbreak of COVID-19].

The novel coronavirus disease 2019 (COVID-19) broke out in December 2019 and has been rapidly escalating throughout the world. Clinical findings show that the patients with either symptomatic or asymptomatic COVID-19 can be a potential source of infection. Although respiratory droplets and close contact are considered to be the main routes of transmission, there is the possibility of aerosol transmission in a relatively closed environment. The nucleic acid of the novel coronavirus can be detected in nasopharyngeal swabs, sputum and other lower respiratory tract secretions, blood, feces, urine and so on, but whether it exists in the semen has not been confirmed. It is reported that the novel coronavirus may affect the testis that highly expresses angiotensin-converting enzyme 2 (ACE2) and theoretically the semen is a possible carrier of the virus considering the fact that it is discharged from the same channel as the urine. Andrology laboratorians are exposed to most of the specimens above, including semen, and some open operations in the laboratory increase the risk of aerosol generation. Therefore, corresponding protective procedures are necessitated in andrology laboratories to reduce the risk of infection during the outbreak of COVID-19. Based on the knowledge and experience available as regards the pandemic and the characteristics of the work in the andrology laboratory, we summarize some biosafety points for andrology laboratorians to attend to during the outbreak of COVID-19.

Bioinspired kirigami metasurfaces as assistive shoe grips.

Falls and subsequent complications are major contributors to morbidity and mortality, especially in older adults. Here, by taking inspiration from claws and scales found in nature, we show that buckling kirigami structures applied to footwear outsoles generate higher friction forces in the forefoot and transversally to the direction of movement. We identified optimal kirigami designs capable of modulating friction for a range of surfaces, including ice, by evaluating the performance of the dynamic kirigami outsoles through numerical simulations and in vitro friction testing, as well as via human-gait force-plate measurements. We anticipate that lightweight kirigami metasurfaces applied to footwear outsoles could help mitigate the risk of slips and falls in a range of environments.