Sequence variations and accessory proteins adapt TMC functions to distinct sensory modalities.

Transmembrane channel-like (TMC) proteins are expressed throughout the animal kingdom and are thought to encode components of ion channels. Mammals express eight TMCs (mTMC1-8), two of which (mTMC1 and mTMC2) are subunits of mechanotransduction channels. C. elegans expresses two TMCs (TMC-1 and TMC-2), which mediate mechanosensation, egg laying, and alkaline sensing. The mechanisms by which nematode TMCs contribute to such diverse physiological processes and their functional relationship to mammalian mTMCs is unclear. Here, we show that association with accessory proteins tunes nematode TMC-1 to divergent sensory functions. In addition, distinct TMC-1 domains enable touch and alkaline sensing. Strikingly, these domains are segregated in mammals between mTMC1 and mTMC3. Consistent with these findings, mammalian mTMC1 can mediate mechanosensation in nematodes, while mTMC3 can mediate alkaline sensation. We conclude that sequence diversification and association with accessory proteins has led to the emergence of TMC protein complexes with diverse properties and physiological functions.

Instant and Multifunctional Nanofibers Loaded with Proanthocyanidins and Hyaluronic Acid for Skincare Applications.

Hyaluronic-acid- and silk-fibroin-based nanofibrous mats loaded with proanthocyanidins and collagen peptides were fabricated as multifunctional facial masks using electrospinning. Their morphology, hygroscopicity and moisture retention, DPPH, ABTS free radical scavenging abilities, and cytocompatibility were investigated. The results showed that the nanofibrous mats were dense and uniform, with an average diameter ranging from 300 to 370 nm. The nanofibrous mats exhibited satisfactory moisture retention, oxidation resistance, biocompatibility, especially excellent DPPH, and ABTS free radical scavenging capacities. DPPH free radical scavenging activity was 90% with 15 mg/L nanofibers, and ABTS free radical scavenging activity was 90% with 0.005 mg/L nanofibers. The nanofibrous mats protected fibroblasts from oxidative stress damage induced by tert-butyl hydroperoxide (t-BHP) and significantly promoted their proliferation. Compared with traditional liquid masks and semi-solid facial masks, the multifunctional nanofibrous mats prepared in this study contained fewer additives, which has significant advantages in terms of safety. The nanofibrous mats were rapidly dissolved within 5 s after being sprayed with water, which facilitated the release and penetration of active ingredients for skincare. Therefore, the multifunctional nanofibrous mats displayed excellent moisture retention, oxidation resistance, and biocompatibility, indicating promising translational potential as facial masks and providing a valuable reference for skincare.

Evolutionary adaptations generally reverse phenotypic plasticity to restore ancestral phenotypes during new environment adaptation in cattle.

Phenotype plasticity and evolution adaptations are the two main ways in which allow populations to deal with environmental changes, but the potential relationship between them remains controversial. Using a reciprocal transplant approach with cattle adapted to the Tibetan Plateau and adjacent lowlands, we aim to investigate the relative contributions of evolutionary processes and phenotypic plasticity in driving both phenotypic and transcriptomic changes under natural conditions. We observed that while numerous genetic transcriptomic changes were evident during the forward adaptation to highland environments, plastic changes predominantly facilitate the transformation of transcriptomes into a preferred state when Tibetan cattle are reintroduced to lowland habitats. Genes with ancestral plasticity are generally reversed by evolutionary adaptations and show a closer expression level to the ancestral stage in evolved Tibetan cattle. A similar trend was also observed at the phenotypes level, with a majority of biochemical and hemorheology phenotypes showing a tendency to revert to their ancestral patterns, suggesting the restoration of ancestral expression levels is a widespread evolutionary trend during adaptation. The findings of our study contribute to the debate regarding the relative contributions of plasticity and genetic changes in mammal environment adaptation. Furthermore, we highlight that the restoration of ancestral phenotypes represents a general pattern in cattle new environment adaptation.

Finite element analysis of endoscopic cross-overtop decompression for single-segment lumbar spinal stenosis based on real clinical cases.

Introduction: For severe degenerative lumbar spinal stenosis (DLSS), the conventional percutaneous endoscopic translaminar decompression (PEID) has some limitations. The modified PEID, Cross-Overtop decompression, ensures sufficient decompression without excessive damage to the facet joints and posterior complex integrity. Objectives: To evaluate the biomechanical properties of Cross-Overtop and provide practical case validation for final decision-making in severe DLSS treatment. Methods: A finite element (FE) model of L4-L5 (M0) was established, and the validity was verified against prior studies. Endo-ULBD (M1), Endo-LOVE (M2), and Cross-Overtop (M3) models were derived from M0 using the experimental protocol. L4-L5 segments in each model were evaluated for the range of motion (ROM) and disc Von Mises stress extremum. The real clinical Cross-Overtop model was constructed based on clinical CT images, disregarding paraspinal muscle influence. Subsequent validation using actual FE analysis results enhances the credibility of the preceding virtual FE analysis. Results: Compared with M0, ROM in surgical models were less than 10°, and the growth rate of ROM ranged from 0.10% to 11.56%, while those of disc stress ranged from 0% to 15.75%. Compared with preoperative, the growth rate of ROM and disc stress were 2.66%-11.38% and 1.38%-9.51%, respectively. The ROM values in both virtual and actual models were less than 10°, verifying the affected segment stability after Cross-Overtop decompression. Conclusion: Cross-Overtop, designed for fully expanding the central canal and contralateral recess, maximizing the integrity of the facet joints and posterior complex, does no significant effect on the affected segmental biomechanics and can be recommended as an effective endoscopic treatment for severe DLSS.

CFAP58 is involved in the sperm head shaping and flagellogenesis of cattle and mice.

CFAP58 is a testis-enriched gene that plays an important role in the sperm flagellogenesis of humans and mice. However, the effect of CFAP58 on bull semen quality and the underlying molecular mechanisms involved in spermatogenesis remain unknown. Here, we identified two single-nucleotide polymorphisms (rs110610797, A>G and rs133760846, G>T) and one indel (g.-1811_ g.-1810 ins147bp) in the promoter of CFAP58 that were significantly associated with semen quality of bulls, including sperm deformity rate and ejaculate volume. Moreover, by generating gene knockout mice, we found for the first time that the loss of Cfap58 not only causes severe defects in the sperm tail, but also affects the manchette structure, resulting in abnormal sperm head shaping. Cfap58 deficiency causes an increase in spermatozoa apoptosis. Further experiments confirmed that CFAP58 interacts with IFT88 and CCDC42. Moreover, it may be a transported cargo protein that plays a role in stabilizing other cargo proteins, such as CCDC42, in the intra-manchette transport/intra-flagellar transport pathway. Collectively, our findings reveal that CFAP58 is required for spermatogenesis and provide genetic markers for evaluating semen quality in cattle.

One-hole split endoscope versus unilateral biportal endoscopy for lumbar spinal stenosis: a retrospective propensity score study.

BACKGROUND: The one-hole split endoscopy (OSE) was first proposed and clinically applied in China in 2019. The aim of this study was to compare the clinical efficacy of one-hole split endoscopy (OSE) and unilateral biportal endoscopy (UBE) for treating lumbar spinal stenosis (LSS). METHODS: One hundred sixty patients with LSS who met the inclusion from November 2020 to August 2022 were analyzed and divided into OSE and UBE groups. The propensity score matching (PSM) method was used to adjust the imbalanced confounding variables between the two groups. After matching, surgical outcomes were recorded, and clinical data, including functional scores and imaging findings, were compared. Functional scores included the visual analog scale of leg pain (VAS-LP) and back pain (VAS-BP), the Japanese Orthopedic Association score (JOA), and the Oswestry Disability Index (ODI). Imaging data included dural sac cross-sectional area (DCSA), lumbar range of motion (ROM), and sagittal translation (ST). RESULTS: After PSM, 104 LSS patients were included in the study, and all covariates were well-balanced between the two groups. Among the matched patients, the OSE showed advantages over the UBE regarding operative time (62.42 ± 4.86 vs. 68.96 ± 4.56) and incision length (2.30 ± 0.14 vs. 2.70 ± 0.15) (P < 0.001). However, differences between the two groups in intraoperative blood loss, hospital length of stay, and complication rates were not statistically significant (P > 0.05). There was no statistically significant difference regarding VAS-BP, VAS-LP, JOA, and ODI between the two groups (P > 0.05). However, all clinical and functional scores significantly improved postoperatively (P < 0.05). Postoperative DCSA of both groups was significantly found to be improved (P < 0.05), ROM and ST remained within the normal range, and no cases of lumbar instability were recorded. According to the modified MacNab criteria, the excellent and good rates in the OSE and UBE groups were 94.23% and 90.38%, respectively, with no statistically significant difference (P = 0.713). CONCLUSION: OSE is an alternative technique to UBE for the treatment of LSS, with similar satisfactory clinical outcomes, shorter operative time, and smaller incision length. Further studies are needed for long-term efficacy.

Plant endophytic fungi exhibit diverse biotransformation pathways of mogrosides and show great potential application in siamenoside I production.

Fungal endophytes, as an untapped resource of glycoside hydrolase biocatalysts, need to be further developed. Mogroside V, the primary active compound in Siraitia grosvenorii fruit, can be converted into other various bioactive mogrosides by selective hydrolysis of glucose residues at C3 and C24 positions. In present study, 20 fungal strains were randomly selected from our endophytic fungal strain library to assess their capability for mogroside V transformation. The results revealed that relatively high rate (30%) endophytic fungal strains exhibited transformative potential. Further analysis indicated that endophytic fungi could produce abundant mogrosides, and the pathways for biotransforming mogroside V showed diverse. Among the given fungal endophytes, Aspergillus sp. S125 almost completely converted mogroside V into the end-products mogroside II A and aglycone within just 2 days of fermentation; Muyocopron sp. A5 produced rich intermediate products, including siamenoside I, and the end-product mogroside II E. Subsequently, we optimized the fermentation conditions for Aspergillus sp. S125 and Muyocopron sp. A5 to evaluate the feasibility of large-scale mogroside V conversion. After optimization, Aspergillus sp. S125 converted 10 g/L of mogroside V into 4.5 g/L of mogroside II A and 3.6 g/L of aglycone after 3 days of fermentation, whereas Muyocopron sp. A5 selectively produced 4.88 g/L of siamenoside I from 7.5 g/L of mogroside V after 36 h of fermentation. This study not only identifies highly effective biocatalytic candidates for mogrosides transformation, but also strongly suggests the potential of plant endophytic fungi as valuable resources for the biocatalysis of natural compounds.

Multi-Dimensional Multiplexed Metasurface Holography by Inverse Design.

Multi-dimensional multiplexed metasurface holography extends holographic information capacity and promises revolutionary advancements for vivid imaging, information storage, and encryption. However, achieving multifunctional metasurface holography by forward design method is still difficult because it relies heavily on Jones matrix engineering, which places high demands on physical knowledge and processing technology. To break these limitations and simplify the design process, here, an end-to-end inverse design framework is proposed. By directly linking the metasurface to the reconstructed images and employing a loss function to guide the update of metasurface, the calculation of hologram can be omitted; thus, greatly simplifying the design process. In addition, the requirements on the completeness of meta-library can also be significantly reduced, allowing multi-channel hologram to be achieved using meta-atoms with only two degrees of freedom, which is very friendly to processing. By exploiting the proposed method, metasurface hologram containing up to 12 channels of multi-wavelength, multi-plane, and multi-polarization is designed and experimentally demonstrated, which exhibits the state-of-the-art information multiplexing capacity of the metasurface composed of simple meta-atoms. This method is conducive to promoting the intelligent design of multifunctional meta-devices, and it is expected to eventually accelerate the application of meta-devices in colorful display, imaging, storage and other fields.

Hybrid Printing of Fully Integrated Microfluidic Devices for Biosensing.

The advent of 3D printing has facilitated the rapid fabrication of microfluidic devices that are accessible and cost-effective. However, it remains a challenge to fabricate sophisticated microfluidic devices with integrated structural and functional components due to limited material options of existing printing methods and their stringent requirement on feedstock material properties. Here, a multi-materials multi-scale hybrid printing method that enables seamless integration of a broad range of structural and functional materials into complex devices is reported. A fully printed and assembly-free microfluidic biosensor with embedded fluidic channels and functionalized electrodes at sub-100 µm spatial resolution for the amperometric sensing of lactate in sweat is demonstrated. The sensors present a sensitive response with a limit of detection of 442 nm and a linear dynamic range of 1-10 mm, which are performance characteristics relevant to physiological levels of lactate in sweat. The versatile hybrid printing method offers a new pathway toward facile fabrication of next-generation integrated devices for broad applications in point-of-care health monitoring and sensing.

The impact of resistance-based training programs on throwing performance and throwing-related injuries in baseball players: A systematic review.

The aim of this systematic review is to assess the effects of structured resistance training programs on the throwing performance and injury risk of baseball players, irrespective of their age or sex. The literature search was carried out on 18/10/2023, utilizing databases that include PubMed, Scopus, and the Web of Science. Our inclusion criteria encompassed research involving baseball players of all ages and sex who had undergone resistance-based training interventions. For comparison, we considered active control groups, irrespective of their exposure to additional training programs. The outcomes under investigation were related to throwing performance (i.e., throwing velocity and accuracy) and injuries associated with throwing. In our review, we exclusively included studies with a two- or multi-arm design. We evaluated the risk of bias using the PEDro scale. Out of the initial pool of 509 studies, we carefully examined 27 full-text articles and ultimately selected and analyzed 16 studies for inclusion in our review. Out of the 12 studies that compared and presented the inferential statistics for the post-training effects of the experimental versus control groups, it was observed that 8 of these studies demonstrated a significantly more favorable impact of the experimental group on enhancing throwing velocity when compared to the control group. Out of the three studies that compared the experimental and control groups in terms of throwing accuracy, only one study showed a significant improvement in the experimental group compared to the control group after the intervention. In conclusion, this systematic review indicates that resistance-based training interventions appear to be effective in enhancing throwing velocity. However, the evidence regarding the efficacy of these interventions in improving throwing accuracy is less robust. It is worth noting that while some experimental conditions may lead to an increase in injury rates, there is limited data available on this aspect, with only a few studies reporting on this variable.

Metformin Preserves Insulin Secretion in Pancreatic ß-cells through FGF21/Akt Pathway In vitro and In vivo.

BACKGROUND: In our previous studies, it was found that metformin can elevate the expression of FGF21 in the peripheral blood of type 2 diabetic rats and improve insulin sensitivity in diabetic rats. However, whether this effect is mediated by increased FGF21 expression in pancreatic islet ß-cells is still unknown. Therefore, this study focuses on the effect of metformin on insulin secretion in pancreatic ß-cells. AIMS: Metformin can effectivly improve insulin resistance. Metformin influencing pancreatic ßcell function is inclusive. In this study, we sought to analyze possible variations in insulin secretion and possible signaling mechanisms after metformin intervention. METHODS: The study employed an in vivo model of a high-fat diet in streptozocin-induced diabetic rats and an in vitro model of rat pancreatic ß-cells (INS-1 cells) that were subjected to damage caused by hyperglycemia and hyperlipidemia. After treating INS-1 cells in normal, high-glucose, and high-glucose+metformin, we measured insulin secretion by glucose-stimulated insulin secretion (GSIS). Insulin was measured using an enzyme-linked immunosorbent assay. FGF21 expression was detected by RT-PCR and Western blot, as well as that p-Akt and t-Akt expression were detected by Western blot in INS-1 cells and diabetic rat islets. Finally, to verify the regulation of the FGF21 /Akt axis in metformin administration, additional experiments were carried out in metformin-stimulated INS-1 cells. RESULTS: High-glucose could significantly stimulate insulin secretion while metformin preserved insulin secretion. Expression of FGF21 and p-Akt was decreased in high-glucose, however, metformin could reverse this effect in INS-1 cells and diabetic rat islets. CONCLUSION: Our results demonstrate a protective role of metformin in preserving insulin secretion through FGF21/Akt signaling in T2DM.

Simulation-aided infrared thermography with decomposition-based noise reduction for detecting defects in ancient polyptychs.

In recent years, the conservation and protection of ancient cultural heritage have received increasing attention, and non-destructive testing (NDT), which can minimize the damage done to the test subject, plays an integral role therein. For instance, NDT through active infrared thermal imaging can be applied to ancient polyptychs, which can realize accurate detection of damage and defects existing on the surface and interior of the polyptychs. In this study, infrared thermography is used for non-invasive investigation and evaluation of two polyptych samples with different pigments and artificial defects, but both reproduced based on a painting by Pietro Lorenzetti (1280/85-1348) using the typical tempera technique of the century. It is noted that, to avoid as far as possible secondary damages done to the ancient cultural heritages, repeated damage-detection experiments are rarely carried out on the test subjects. To that end, numerical simulation is used to reveal the heat transfer properties and temperature distributions, as to perform procedural verification and reduce the number of experiments that need to be conducted on actual samples. Technique-wise, to improve the observability of the experimental results, a total variation regularized low-rank tensor decomposition algorithm is implemented to reduce the background noise and improve the contrast of the images. Furthermore, the efficacy of image processing is quantified through the structural-similarity evaluation.

TOR-mediated Ypt1 phosphorylation regulates autophagy initiation complex assembly.

The regulation of autophagy initiation is a key step in autophagosome biogenesis. However, our understanding of the molecular mechanisms underlying the stepwise assembly of ATG proteins during this process remains incomplete. The Rab GTPase Ypt1/Rab1 is recognized as an essential autophagy regulator. Here, we identify Atg23 and Atg17 as binding partners of Ypt1, with their direct interaction proving crucial for the stepwise assembly of autophagy initiation complexes. Disruption of Ypt1-Atg23 binding results in significantly reduced Atg9 interactions with Atg11, Atg13, and Atg17, thus preventing the recruitment of Atg9 vesicles to the phagophore assembly site (PAS). Likewise, Ypt1-Atg17 binding contributes to the PAS recruitment of Ypt1 and Atg1. Importantly, we found that Ypt1 is phosphorylated by TOR at the Ser174 residue. Converting this residue to alanine blocks Ypt1 phosphorylation by TOR and enhances autophagy. Conversely, the Ypt1S174D phosphorylation mimic impairs both PAS recruitment and activation of Atg1, thus inhibiting subsequent autophagy. Thus, we propose TOR-mediated Ypt1 as a multifunctional assembly factor that controls autophagy initiation via its regulation of the stepwise assembly of ATG proteins.

Effects of use motivations and alexithymia on smartphone addiction: mediating role of insecure attachment.

Background and objectives: Concern exists regarding the potential negative consequences of smartphone addiction among adolescents. This study investigated the effect of use motivations and alexithymia on smartphone addiction among adolescents with two insecure attachment styles, namely, anxious and avoidant attachment. These attachment styles were regarded as mediating variables. Methods: Self-report measures were used to assess use motivations, alexithymia, insecure attachment and smartphone addiction. Data were collected from 748 junior high school students (382 males and 366 females) in northeastern China. Structural equation modeling was used to test our hypothesis that use motivations and alexithymia are directly associated with smartphone addiction and also through the mediation of attachment insecurities. Results: The structural equation modeling results showed a strong and positive correlation between use motivation and smartphone addiction, with avoidant attachment mediating such a relationship. Meanwhile, the two components of alexithymia, difficulty identifying feelings and externally oriented thinking, positively predicted smartphone addiction, with avoidant attachment serving as a mediator of this effect. In addition, the mediation analysis results demonstrated that attachment anxiety mediated the connection between escape drive, extrinsically focused thought, and smartphone addiction. Conclusion: Findings describe how attachment insecurities, smartphone use motivations, and alexithymia can interact with one another to predict smartphone addiction. Smartphone use motivation types and alexithymia symptoms should be taken into consideration when designing targeted intervention programs for smartphone addiction to address the different attachment needs of adolescents, which would be helpful to reduce their smartphone addiction behaviors.

Pre-transjugular-intrahepatic-portosystemic-shunt measurement of hepatic venous pressure gradient and its clinical application: A comparison study.

BACKGROUND: It is controversial whether transjugular intrahepatic portosystemic shunt (TIPS) placement can improve long-term survival. AIM: To assess whether TIPS placement improves survival in patients with hepatic-venous-pressure-gradient (HVPG) ≥ 16 mmHg, based on HVPG-related risk stratification. METHODS: Consecutive variceal bleeding patients treated with endoscopic therapy + nonselective ß-blockers (NSBBs) or covered TIPS placement were retrospectively enrolled between January 2013 and December 2019. HVPG measurements were performed before therapy. The primary outcome was transplant-free survival; secondary endpoints were rebleeding and overt hepatic encephalopathy (OHE). RESULTS: A total of 184 patients were analyzed (mean age, 55.27 years ± 13.86, 107 males; 102 in the EVL+NSBB group, 82 in the covered TIPS group). Based on the HVPG-guided risk stratification, 70 patients had HVPG < 16 mmHg, and 114 patients had HVPG ≥ 16 mmHg. The median follow-up time of the cohort was 49.5 mo. There was no significant difference in transplant-free survival between the two treatment groups overall (hazard ratio [HR], 0.61; 95% confidence interval [CI]: 0.35-1.05; P = 0.07). In the high-HVPG tier, transplant-free survival was higher in the TIPS group (HR, 0.44; 95%CI: 0.23-0.85; P = 0.004). In the low-HVPG tier, transplant-free survival after the two treatments was similar (HR, 0.86; 95%CI: 0.33-0.23; P = 0.74). Covered TIPS placement decreased the rate of rebleeding independent of the HVPG tier (P < 0.001). The difference in OHE between the two groups was not statistically significant (P = 0.09; P = 0.48). CONCLUSION: TIPS placement can effectively improve transplant-free survival when the HVPG is greater than 16 mmHg.

High-throughput printing of combinatorial materials from aerosols.

The development of new materials and their compositional and microstructural optimization are essential in regard to next-generation technologies such as clean energy and environmental sustainability. However, materials discovery and optimization have been a frustratingly slow process. The Edisonian trial-and-error process is time consuming and resource inefficient, particularly when contrasted with vast materials design spaces1. Whereas traditional combinatorial deposition methods can generate material libraries2,3, these suffer from limited material options and inability to leverage major breakthroughs in nanomaterial synthesis. Here we report a high-throughput combinatorial printing method capable of fabricating materials with compositional gradients at microscale spatial resolution. In situ mixing and printing in the aerosol phase allows instantaneous tuning of the mixing ratio of a broad range of materials on the fly, which is an important feature unobtainable in conventional multimaterials printing using feedstocks in liquid-liquid or solid-solid phases4-6. We demonstrate a variety of high-throughput printing strategies and applications in combinatorial doping, functional grading and chemical reaction, enabling materials exploration of doped chalcogenides and compositionally graded materials with gradient properties. The ability to combine the top-down design freedom of additive manufacturing with bottom-up control over local material compositions promises the development of compositionally complex materials inaccessible via conventional manufacturing approaches.

Dual attention fusion UNet for COVID-19 lesion segmentation from CT images.

BACKGROUND: Chest CT scan is an effective way to detect and diagnose COVID-19 infection. However, features of COVID-19 infection in chest CT images are very complex and heterogeneous, which make segmentation of COVID-19 lesions from CT images quite challenging. OBJECTIVE: To overcome this challenge, this study proposes and tests an end-to-end deep learning method called dual attention fusion UNet (DAF-UNet). METHODS: The proposed DAF-UNet improves the typical UNet into an advanced architecture. The dense-connected convolution is adopted to replace the convolution operation. The mixture of average-pooling and max-pooling acts as the down-sampling in the encoder. Bridge-connected layers, including convolution, batch normalization, and leaky rectified linear unit (leaky ReLU) activation, serve as the skip connections between the encoder and decoder to bridge the semantic gap differences. A multiscale pyramid pooling module acts as the bottleneck to fit the features of COVID-19 lesion with complexity. Furthermore, dual attention feature (DAF) fusion containing channel and position attentions followed the improved UNet to learn the long-dependency contextual features of COVID-19 and further enhance the capacity of the proposed DAF-UNet. The proposed model is first pre-trained on the pseudo label dataset (generated by Inf-Net) containing many samples, then fine-tuned on the standard annotation dataset (provided by the Italian Society of Medical and Interventional Radiology) with high-quality but limited samples to improve performance of COVID-19 lesion segmentation on chest CT images. RESULTS: The Dice coefficient and Sensitivity are 0.778 and 0.798 respectively. The proposed DAF-UNet has higher scores than the popular models (Att-UNet, Dense-UNet, Inf-Net, COPLE-Net) tested using the same dataset as our model. CONCLUSION: The study demonstrates that the proposed DAF-UNet achieves superior performance for precisely segmenting COVID-19 lesions from chest CT scans compared with the state-of-the-art approaches. Thus, the DAF-UNet has promising potential for assisting COVID-19 disease screening and detection.

Coordinated alternation of DNA methylation and alternative splicing of PBRM1 affect bovine sperm structure and motility.

DNA methylation and gene alternative splicing drive spermatogenesis. In screening DNA methylation markers and transcripts related to sperm motility, semen from three pairs of full-sibling Holstein bulls with high and low motility was subjected to reduced representation bisulphite sequencing. A total of 948 DMRs were found in 874 genes (gDMRs). Approximately 89% of gDMR-related genes harboured alternative splicing events, including SMAD2, KIF17, and PBRM1. One DMR in exon 29 of PBRM1 with the highest 5mC ratio was found, and hypermethylation in this region was related to bull sperm motility. Furthermore, alternative splicing events at exon 29 of PBRM1 were found in bull testis, including PBRM1-complete, PBRM1-SV1 (exon 28 deletion), and PBRM1-SV2 (exons 28-29 deletion). PBRM1-SV2 exhibited significantly higher expression in adult bull testes than in newborn bull testes. In addition, PBRM1 was localized to the redundant nuclear membrane of bull sperm, which might be related to sperm motility caused by sperm tail breakage. Therefore, the hypermethylation of exon 29 may be associated with the production of PBRM1-SV2 in spermatogenesis. These findings indicated that DNA methylation alteration at specific loci could regulate gene splicing and expression and synergistically alter sperm structure and motility.

Investigation of risk factors associated with impaired glucose regulation: Using the momentum equation to assess the impact of risk factors on community residents.

Objective: To identify risk factors for impaired glucose regulation (IGR) and assess their impact on community residents, this study used a questionnaire to conduct cross-sectional surveys and analysis. Methods: Overall, 774 residents of an urban community in northern China (Jian city) participated in this study. Trained investigators conducted surveys using questionnaires. Based on their medical history, respondents were divided into three glucose status groups as follows: normal (NGT), IGR, and diabetes mellitus (DM). Statistical analysis of survey data was performed using SPSS v. 22.0. Results: Age, hypertension, family history of diabetes (FHD), dyslipidemia, obesity, and cardiovascular and cerebral disease (CVD) were positively correlated with IGR in men and women. IGR was negatively correlated with a sedentary lifestyle in men and positively correlated with being overweight in women. The number of type 2 diabetes mellitus (T2D) risk factors per subject was positively correlated with age in the NGT group. Glucose status deteriorated with increasing age and the number of risk factors. FHD was the strongest risk factor in both men and women. Conclusions: Prevention of IGR includes weight control, physical activity, and prevention of hypertension and dyslipidemia, especially in subjects with FHD.

UFL1, a UFMylation E3 ligase, plays a crucial role in multiple cellular stress responses.

The UFM1 conjugation system(UFMylation)is a novel type of ubiquitin-like system that plays an indispensable role in maintaining cell homeostasis under various cellular stress. Similar to ubiquitination, UFMylation consists of a three-step enzymatic reaction with E1-like enzymes ubiquitin-like modifier activating enzyme5 (UBA5), E2-like enzymes ubiquitin-fold modifier-conjugating enzyme 1(UFC1), and E3-like ligase UFM1-specific ligase 1 (UFL1). As the only identified E3 ligase, UFL1 is responsible for specific binding and modification of the substrates to mediate numerous hormone signaling pathways and endocrine regulation under different physiological or pathological stress, such as ER stress, genotoxic stress, oncogenic stress, and inflammation. Further elucidation of the UFL1 working mechanism in multiple cellular stress responses is essential for revealing the disease pathogenesis and providing novel potential therapeutic targets. In this short review, we summarize the recent advances in novel UFL1 functions and shed light on the potential challenges ahead, thus hopefully providing a better understanding of UFMylation-mediated cellular stress.