Islr regulates satellite cells asymmetric division through the SPARC/p-ERK1/2 signaling pathway.

Satellite cells (SCs) are adult muscle stem cells responsible for muscle regeneration after acute and chronic muscle injuries. The balance between stem cell self-renewal and differentiation determines the kinetics and efficiency of skeletal muscle regeneration. This study assessed the function of Islr in SC asymmetric division. The deletion of Islr reduced muscle regeneration in adult mice by decreasing the SC pool. Islr is pivotal for SC proliferation, and its deletion promoted the asymmetric division of SCs. A mechanistic search revealed that Islr bound to and degraded secreted protein acidic and rich in cysteine (SPARC), which activated p-ERK1/2 signaling required for asymmetric division. These findings demonstrate that Islr is a key regulator of SC division through the SPARC/p-ERK1/2 signaling pathway. These data provide a basis for treating myopathy.

Lysyl Oxidase 3 Is a Dual-Specificity Enzyme Involved in STAT3 Deacetylation and Deacetylimination Modulation.

In mammalian cells, histone deacetylase (HDAC) and Sirtuin (SIRT) are two families responsible for removing acetyl groups from acetylated proteins. Here, we describe protein deacetylation coupled with deacetylimination as a function of lysyl oxidase (LOX) family members. LOX-like 3 (Loxl3) associates with Stat3 in the nucleus to deacetylate and deacetyliminate Stat3 on multiple acetyl-lysine sites. Surprisingly, Loxl3 N-terminal scavenger receptor cysteine-rich (SRCR) repeats, rather than the C-terminal oxidase catalytic domain, represent the major deacetylase/deacetyliminase activity. Loxl3-mediated deacetylation/deacetylimination disrupts Stat3 dimerization, abolishes Stat3 transcription activity, and restricts cell proliferation. In Loxl3-/- mice, Stat3 is constitutively acetylated and naive CD4+ T cells are potentiated in Th17/Treg cell differentiation. When overexpressed, the SRCR repeats from other LOX family members can catalyze protein deacetylation/deacetylimination. Thus, our findings delineate a hitherto-unknown mechanism of protein deacetylation and deacetylimination catalyzed by lysyl oxidases.

Surface Nanostructures Promote Droplet Splash on Hot Substrates.

Splash, one of the most visually apparent droplet dynamics, can manifest on any surface above a certain impact velocity, regardless of surface wettability. Previous studies demonstrate that elevating the substrate temperature can suppress droplet splash, which is unfavorable for many practical applications, such as spray cooling and combustion. Here, we report that the suppression effect of substrate temperature on splash is nullified by utilizing surfaces with nanostructures. By manipulating air evacuation time through surface nanostructures, we have identified a pathway for precise control over the splash threshold and the ability to tailor the dependence of the splash onset on surface temperature. We further propose a theoretical criterion to determine different splash regimes by considering the competition between air evacuation and the development of flow instabilities. Our findings underscore the crucial role of nanostructures in splash dynamics, offering valuable insights for the control of splash in various industrial scenarios.

XPO1 inhibition displays anti-leukemia efficacy against DNMT3A-mutant acute myeloid leukemia via downregulating glutathione pathway.

Acute myeloid leukemia (AML) patients with DNA methyltransferase 3A (DNMT3A) mutation display poor prognosis, and targeted therapy is not available currently. Our previous study identified increased expression of Exportin1 (XPO1) in DNMT3AR882H AML patients. Therefore, we further investigated the therapeutic effect of XPO1 inhibition on DNMT3AR882H AML. Three types of DNMT3AR882H AML cell lines were generated, and XPO1 was significantly upregulated in all DNMT3AR882H cells compared with the wild-type (WT) cells. The XPO1 inhibitor selinexor displayed higher potential in the inhibition of proliferation, promotion of apoptosis, and blockage of the cell cycle in DNMT3AR882H cells than WT cells. Selinexor also significantly inhibited the proliferation of subcutaneous tumors in DNMT3AR882H AML model mice. Primary cells with DNMT3A mutations were more sensitive to selinexor in chemotherapy-naive AML patients. RNA sequencing of selinexor treated AML cells revealed that the majority of metabolic pathways were downregulated after selinexor treatment, with the most significant change in the glutathione metabolic pathway. Glutathione inhibitor L-Buthionine-(S, R)-sulfoximine (BSO) significantly enhanced the apoptosis-inducing effect of selinexor in DNMT3AWT/DNMT3AR882H AML cells. In conclusion, our work reveals that selinexor displays anti-leukemia efficacy against DNMT3AR882H AML via downregulating glutathione pathway. Combination of selinexor and BSO provides novel therapeutic strategy for AML treatment.

VRK1 promotes DNA-induced type I interferon production.

BACKGROUND: Type I interferons (IFNs) are an essential class of cytokines with antitumor, antiviral and immunoregulatory effects. However, over-productive the type I IFNs are tightly associated with autoimmune disorders. Thus, the induction of type I interferons is precisely regulated to maintain immune hemostasis. This study aimed to identify a novel regulator of type I interferon signaling. METHODS AND RESULTS: Primary BMDMs, isolated from mice, and human cell lines (HEK293 cells, Hela cells) and murine cell line (MEF cells) were cultured to generate in vitro models. After knockdown VRK1, real-time PCR and dual-luciferase reporter assay were performed to determine the expression level of the type I IFNs and ISGs following HTDNA and Poly (dA:dT) stimulation. Additionally, cells were treated with the VRK1 inhibitor, and the impact of VRK1 inhibition was detected. Upon HTDNA and Poly (dA:dT) stimulation, knockdown of VRK1 attenuated the induction of the type I IFNs and ISGs. Consistently, VRK-IN-1, a potent and selective VRK1 inhibitor, significantly suppressed the induction of the type I IFNs and ISGs in human and murine cell lines. Further, VRK-IN-1 inhibited induction of the type I IFNs in mouse primary BMDMs. Intriguingly, VRK1 potentiated the cGAS-STING- IFN-I axis response at STING level. CONCLUSIONS: Our study reveals a novel function of VRK1 in regulating the production of type I IFNs. VRK-IN-1 might be a potential lead compound for suppressing aberrant type I IFNs in autoimmune disorders.

Near-field coupling of interlayer excitons in MoSe2/WSe2 heterobilayers to surface plasmon polaritons.

Two-dimensional (2D) transition metal dichalcogenides have emerged as promising quantum functional blocks benefitting from their unique combination of spin, valley, and layer degrees of freedom, particularly for the tremendous flexibility of moiré superlattices formed by van der Waals stacking. These degrees of freedom coupled with the enhanced Coulomb interaction in 2D structures allow excitons to serve as on-chip information carriers. However, excitons are spatially circumscribed due to their low mobility and limited lifetime. One way to overcome these limitations is through the coupling of excitons with surface plasmon polaritons (SPPs), which facilitates an interaction between remote quantum states. Here, we showcase the successful coupling of SPPs with interlayer excitons in molybdenum diselenide/tungsten diselenide heterobilayers. Our results indicate that the valley polarization can be efficiently transferred to SPPs, enabling preservation of polarization information even after propagating tens of micrometers.

SLCO1B1 Polymorphisms are Associated with the Susceptibility to Pulmonary Tuberculosis in Chinese Females.

This study aimed to evaluate the role of SLCO1B1 polymorphisms in pulmonary tuberculosis (PTB) risk among Chinese patients. This study comprised 600 PTB patients (mean age: 37.43 ± 12.73 years) and 600 healthy controls (mean age: 37.39 ± 12.57 years) from a Chinese population. The SLCO1B1 rs2306283 and rs4149056 polymorphisms were detected using TaqMan genotyping assay. Chi-square (χ2) test was applied to calculate the Hardy-Weinberg Equilibrium (HWE) among controls. Logistic regression analysis was used to examine the odds ratio (OR) and 95% confidence interval (CI). After adjustment for age and gender, the frequency of rs4149056-C was significantly higher in PTB group (P = 0.017, OR = 1.375, 95% CI 1.058-1.786); meanwhile, rs4149056 was associated with increased PTB risk in dominant model (P = 0.015, OR = 1.424, 95% CI 1.072-1.892). The frequency and genotype of rs2306283 showed no significant difference between the two groups. In stratified analysis, rs2306283-GG showed notable susceptibility to PTB (P = 0.027, OR = 1.563, 95% CI 1.051-2.323 in recessive model) in females; rs4149056-C was also significantly higher in female PTB group (P = 0.039, OR = 1.741, 95% CI 1.028-2.948). Neither of rs2306283 and rs4149056 polymorphisms was associated with PTB risk in males. A haplotype analysis showed that patients carrying at least one SLCO1B1*15 haplotype had higher PTB risk (P = 0.004, OR = 1.527, 95% CI 1.145-2.034). SLCO1B1 polymorphisms are associated with the susceptibility to pulmonary tuberculosis in Chinese females.

PS-MPs promotes the progression of inflammation and fibrosis in diabetic nephropathy through NLRP3/Caspase-1 and TGF-ß1/Smad2/3 signaling pathways.

BACKGROUND: Diabetic nephropathy (DN) is a prevalent chronic microvascular complication of diabetes and the leading cause of end-stage renal disease (ESRD). Understanding the progressive etiology of DN is critical for the development of effective health policies and interventions. Recent research indicated that polystyrene microplastics (PS-MPs) contaminate our diets and accumulate in various organs, including the liver, kidneys, and muscles. METHODS: In this study, ten-week-old db/db mice and db/m mice were fed. Besides, db/db mice were divided into two groups: PS-MPs group (oral administration of 0.5 µm PS-MPs) and an H2O group, and they were fed for three months. A type II diabetes model was established using db/db mice to investigate the effects of PS-MPs on body weight, blood glucose level, renal function, and renal fibrosis. RESULTS: The results demonstrated that PS-MPs significantly exacerbated various biochemical indicators of renal tissue damage, including fasting blood glucose, serum creatinine, blood urea nitrogen, and blood uric acid. Additionally, PS-MPs worsened the pathological alterations and degree of fibrosis in renal tissue. An increased oxidative stress state and elevated levels of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and monocyte chemoattractant protein-1 (MCP-1) were identified. Furthermore, PS-MPs significantly enhanced renal fibrosis by inhibiting the transition from epithelial cells to mesenchymal cells, specifically through the inhibition of the TGF-ß/Smad signaling pathway. The expression levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, and cleaved Caspase-1, which are inflammasome proteins, were significantly elevated in the PS-MPs group. CONCLUSION: The findings suggested that PS-MPs could aggravate kidney injury and renal fibrosis in db/db mice by promoting NLRP3/Caspase-1 and TGF-ß1/Smads signaling pathways. These findings had implications for elucidating the role of PS-MPs in DN progression, underscoring the necessity for additional research and public health interventions.

Lactoferrin deficiency during lactation increases the risk of depressive-like behavior in adult mice.

BACKGROUND: Lactoferrin is an active protein in breast milk that plays an important role in the growth and development of infants and is implicated as a neuroprotective agent. The incidence of depression is currently increasing, and it is unclear whether the lack of lactoferrin during lactation affects the incidence of depressive-like behavior in adulthood. RESULTS: Lack of lactoferrin feeding during lactation affected the barrier and innate immune functions of the intestine, disrupted the intestinal microflora, and led to neuroimmune dysfunction and neurodevelopmental delay in the hippocampus. When exposed to external stimulation, adult lactoferrin feeding-deficient mice presented with worse depression-like symptoms; the mechanisms involved were activation of the LPS-TLR4 signalling pathway in the intestine and hippocampus, reduced BDNF-CREB signaling pathway in hippocampus, increased abundance of depression-related bacteria, and decreased abundance of beneficial bacteria. CONCLUSIONS: Overall, our findings reveal that lactoferrin feeding deficient during lactation can increase the risk of depressive-like behavior in adults. The mechanism is related to the regulatory effect of lactoferrin on the development of the "microbial-intestinal-brain" axis.

Microplastics cause hepatotoxicity in diabetic mice by disrupting glucolipid metabolism via PP2A/AMPK/HNF4A and promoting fibrosis via the Wnt/ß-catenin pathway.

In recent years, microplastics (MPs) have gained significant attention as a persistent environmental pollutant resulting from the decomposition of plastics, leading to their accumulation in the human body. The liver, particularly of individuals with type 2 diabetes mellitus (T2DM), is known to be more susceptible to the adverse effects of environmental pollutants. Therefore, to investigate the potential impact of MPs on the liver of diabetic mice and elucidate the underlying toxicological mechanisms, we exposed db/db mice to 0.5 µm MPs for 3 months. Our results revealed that MPs exposure resulted in several harmful effects, including decreased body weight, disruption of liver structure and function, elevated blood glucose levels, impaired glucose tolerance, and increased glycogen accumulation in the hepatic tissue of the mice. Furthermore, MPs exposure was found to promote hepatic gluconeogenesis by perturbing the PP2A/AMPK/HNF4A signaling pathway. In addition, MPs disrupt redox balance, leading to oxidative damage in the liver. This exposure also disrupted hepatic lipid metabolism, stimulating lipid synthesis while inhibiting catabolism, ultimately resulting in the development of fatty liver. Moreover, MPs were found to induce liver fibrosis by activating the Wnt/ß-catenin signaling pathway. Furthermore, MPs influenced adaptive thermogenesis in brown fat by modulating the expression of uncoupling protein 1 (UCP1) and genes associated with mitochondrial oxidative respiration thermogenesis in brown fat. In conclusion, our study demonstrates that MPs induce oxidative damage in the liver, disturb glucose and lipid metabolism, promote hepatic fibrosis, and influence adaptive thermogenesis in brown fat in diabetic mice. These findings underscore the potential adverse effects of MPs on liver health in individuals with T2DM and highlight the importance of further research in this area.

Improvement of Phased Antenna Array Applied in Focused Microwave Breast Hyperthermia.

Focused microwave breast hyperthermia (FMBH) employs a phased antenna array to perform beamforming that can focus microwave energy at targeted breast tumors. Selective heating of the tumor endows the hyperthermia treatment with high accuracy and low side effects. The effect of FMBH is highly dependent on the applied phased antenna array. This work investigates the effect of polarizations of antenna elements on the microwave-focusing results by simulations. We explore two kinds of antenna arrays with the same number of elements using different digital realistic human breast phantoms. The first array has all the elements' polarization in the vertical plane of the breast, while the second array has half of the elements' polarization in the vertical plane and the other half in the transverse plane, i.e., cross polarization. In total, 96 sets of different simulations are performed, and the results show that the second array leads to a better focusing effect in dense breasts than the first array. This work is very meaningful for the potential improvement of the antenna array for FMBH, which is of great significance for the future clinical applications of FMBH. The antenna array with cross polarization can also be applied in microwave imaging and sensing for biomedical applications.

A novel approach for anterior cruciate ligament tibial avulsion fracture: arthroscopic modified suture bridge fixation technique.

INTRODUCTION: Anterior cruciate ligament (ACL) tibial avulsion fracture is a rare injury, which usually happens in adults with traffic accidents or sports injuries. Surgery interventions are common treatment methods, they can restore knee function and help to return to normal life. In this study, we described an arthroscopic modified suture bridge fixation technique for ACL tibial avulsion fractures and explored the feasibility and therapeutic effects. MATERIALS AND METHODS: This retrospective study reviewed data from January 2020 to May 2022. Data were collected on 18 patients (10 males and 8 females) with ACL tibial avulsion fractures and underwent arthroscopic modified suture bridge fixation technique. The study analyzed surgical data about intraoperative blood loss, operation time, hospital stay, fracture healing time, and visual analog scale (VAS). Functional evaluation of the knee joint was performed using the anterior drawer test, Lysholm knee scoring scale, International Knee Documentation Committee (IKDC), and knee range of motion (ROM). RESULTS: All 18 patients were followed up between 12 and 20 months, with an average of 15.22 ± 1.96 months. The intraoperative blood loss was approximately 15-40 mL, averaging 25.78 ± 6.19 mL. The operation time was 65-85 min, with a mean of 74.89 ± 4.86 min. The hospital stay of patients was 3-5 days, with a mean of 3.89 ± 0.76 days. The mean fracture healing time was 8-12 weeks after surgery, with a mean of 9.22 ± 1.7 weeks. All incisions healed grade I without infection. There were no internal fixation failures, neurovascular injuries, and lower extremity deep venous thrombosis. The anterior drawer test was negative in all patients. At the final follow-up, the mean VAS score was 0-3, averaging 1.56 ± 0.71. The Lysholm score of the injured knee was 89-96, with an average of 92.50 ± 2.50; the IKDC score was 88-93, with an average of 90.44 ± 1.89; the knee ROM was 110-126°, with an average of 120.67° ± 4.31°. CONCLUSION: Results demonstrated that the modified suture bridge fixation technique under arthroscope could provide reliable fixation and favorable clinical effects for ACL tibial avulsion fractures. This is a simple, minimally invasive, effective, and clinically applicable surgical method for ACL tibial avulsion fracture.

TCGAplot: an R package for integrative pan-cancer analysis and visualization of TCGA multi-omics data.

BACKGROUND: Pan-cancer analysis examines both the commonalities and heterogeneity among genomic and cellular alterations across numerous types of tumors. Pan-cancer analysis of gene expression, tumor mutational burden (TMB), microsatellite instability (MSI), and tumor immune microenvironment (TIME), and methylation becomes available based on the multi-omics data from The Cancer Genome Atlas Program (TCGA). Some online tools provide analysis of gene and protein expression, mutation, methylation, and survival for TCGA data. However, these online tools were either Uni-functional or were not able to perform analysis of user-defined functions. Therefore, we created the TCGAplot R package to facilitate perform pan-cancer analysis and visualization of the built-in multi-omic TCGA data. RESULTS: TCGAplot provides several functions to perform pan-cancer paired/unpaired differential gene expression analysis, pan-cancer correlation analysis between gene expression and TMB, MSI, TIME, and promoter methylation. Functions for visualization include paired/unpaired boxplot, survival plot, ROC curve, heatmap, scatter, radar chart, and forest plot. Moreover, gene set based pan-cancer and tumor specific analyses were also available. Finally, all these built-in multi-omic data could be extracted for implementation for user-defined functions, making the pan-cancer analysis much more convenient.\ CONCLUSIONS: We developed an R-package for integrative pan-cancer analysis and visualization of TCGA multi-omics data. The source code and pre-built package are available at GitHub ( https://github.com/tjhwangxiong/TCGAplot ).

Four-channel joint-polarization-frequency-multiplexing encryption meta-hologram based on dual-band polarization multiplexing meta-atoms.

Holography is an advanced imaging technology where image information can be reconstructed without a lens. Recently, multiplexing techniques have been widely adapted to realize multiple holographic images or functionalities in a meta-hologram. In this work, a reflective four-channel meta-hologram is proposed to further increase the channel capacity by simultaneously implementing frequency and polarization multiplexing. Compared to the single multiplexing technique, the number of channels achieves a multiplicative growth of the two multiplexing techniques, as well as allowing meta-devices to possess cryptographic characteristics. Specifically, spin-selective functionalities for circular polarizations can be achieved at lower frequency, while different functionalities can be obtained at higher frequency under different linearly polarized incidences. As an illustrative example, a four-channel joint-polarization-frequency-multiplexing meta-hologram is designed, fabricated, and characterized. The measured results agree well with the numerically calculated and full-wave simulated ones, which provides the proposed method with great potential in numerous opportunities such as multi-channel imaging and information encryption technology.

Boosting photocatalytic performances of lamellar BiVO4by constructing S-scheme heterojunctions with AgBr for efficient charge transfer.

Successful construction of heterojunction can improve the utilization efficiency of solar light by broadening the absorption range, facilitating charge-carrier separation, promoting carrier transportation and influencing surface-interface reaction. Herein, visible-light-driven AgBr was deposited on the surface of lamellar BiVO4which was prepared by a facile hydrothermal process to improve charge carrier separation, and subsequent photocatalytic effectiveness. The catalyst with an optimal AgBr/BiVO4ratio exhibited a superbly enhanced photocatalytic decolorization ability (about 6.85 times higher than that of pure BiVO4) and high stability after four cycles. The unique photocatalytic mechanism of S-scheme carrier migration was investigated on the bases of radical trapping tests and photo/electrochemical characterizations. Results showed that the enhanced migration strategy and intimately interfacial collaboration guaranteed the effective charge carriers separation/transfer, leading to magnificent photocatalytic performance as well as excellent stability.

Homozygous mutations in CCDC34 cause male infertility with oligoasthenoteratozoospermia in humans and mice.

BACKGROUND: Oligoasthenoteratozoospermia is a typical feature of sperm malformations leading to male infertility. Only a few genes have been clearly identified as pathogenic genes of oligoasthenoteratozoospermia. METHODS AND RESULTS: Here, we identified a homozygous frameshift variant (c.731dup, p.Asn244Lysfs*3) in CCDC34, which is preferentially expressed in the human testis, using whole-exome sequencing in a cohort of 100 Chinese men with multiple morphological abnormalities of the sperm flagella (MMAF). In an additional cohort of 167 MMAF-affected men from North Africa, Iran and France, we identified a second subject harbouring a homozygous CCDC34 frameshift variant (c.799_817del, p.Glu267Lysfs*72). Both affected men presented a typical MMAF phenotype with an abnormally low sperm concentration (ie, oligoasthenoteratozoospermia). Transmission electron microscopy analysis of the sperm flagella affected by CCDC34 deficiency further revealed dramatic disorganisation of the axoneme. Immunofluorescence assays of the spermatozoa showed that CCDC34 deficiency resulted in almost absent staining of CCDC34 and intraflagellar transport-B complex-associated proteins (such as IFT20 and IFT52). Furthermore, we generated a mouse Ccdc34 frameshift mutant using CRISPR-Cas9 technology. Ccdc34-mutated (Ccdc34mut/mut ) male mice were sterile and presented oligoasthenoteratozoospermia with typical MMAF anomalies. Intracytoplasmic sperm injection has good pregnancy outcomes in both humans and mice. CONCLUSIONS: Our findings support that CCDC34 is crucial to the formation of sperm flagella and that biallelic deleterious mutations in CCDC34/Ccdc34 cause male infertility with oligoasthenoteratozoospermia in humans and mice.

Recent Progress in Metal Oxide-Based Photocatalysts for CO2 Reduction to Solar Fuels: A Review.

One of the challenges in developing practical CO2 photoconversion catalysts is the design of materials with a low cost, high activity and good stability. In this paper, excellent photocatalysts based on TiO2, WO3, ZnO, Cu2O and CeO2 metal oxide materials, which are cost-effective, long-lasting, and easy to fabricate, are evaluated. The characteristics of the nanohybrid catalysts depend greatly on their architecture and design. Thus, we focus on outstanding materials that offer effective and practical solutions. Strategies to improve CO2 conversion efficiency are summarized, including heterojunction, ion doping, defects, sensitization and morphology control, which can inspire the future improvement in photochemistry. The capacity of CO2 adsorption is also pivotal, which varies with the morphological and electronic structures. Forms of 0D, 1D, 2D and 3DOM (zero/one/two-dimensional- and three-dimensional-ordered macroporous, respectively) are involved. Particularly, the several advantages of the 3DOM material make it an excellent candidate material for CO2 conversion. Hence, we explain its preparation method. Based on the discussion, new insights and prospects for designing high-efficient metallic oxide photocatalysts to reduce CO2 emissions are presented.

Phenolic Compounds from Sonchus arvensis Linn. and Hemerocallis citrina Baroni. Inhibit Sucrose and Stearic Acid Induced Damage in Caenorhabditis elegans.

Sonchus arvensis Linn. and Hemerocallis citrina Baroni. have been reported to improve body resistance. However, the underlying mechanism is not clear. In this study, Sonchus arvensis Linn. phenolic compounds (SAP) and Hemerocallis citrina Baroni. phenolic compounds (HCP) were extracted and their protective effects in Caenorhabditis elegans evaluated. SAP and HCP showed considerably different phenolic compositions. In the normal C. elegans model, HCP exhibited better effects in promoting growth than SAP. In the sucrose-incubated C. elegans model, both SAP and HCP showed positive effects against the high-sucrose-induced damage. In the stearic acid-incubated C. elegans model, both SAP and HCP improved lifespan, reproductive ability and growth, while HCP had a more evident effect than SAP on reproductive ability. The TGF-ß signaling pathway was confirmed to be involved in the protective effects of SAP and HCP. The antioxidant ability of SAP was also found to be related to skn-1. Our study shows that both SAP and HCP have protective effects against high sucrose- or high stearic acid-induced damage.

[Compound Amino Acid Capsule (8-11) combined with L-carnitine for the treatment of asthenospermia].

OBJECTIVE: To observe the clinical effect of combined application of Compound Amino Acid Capsule (8-11) (CAAC8-11) and L-carnitine (LC) in the treatment of idiopathic asthenospermia (IAS), and to explore its possible therapeutic mechanism. METHODS: Based on the principle of double-blind and control, we selected 120 cases of IAS meeting the diagnostic criteria of asthenospermia in the WHO Manual for the Examination and Processing of Human Semen (5th Ed) and randomly divided them into three groups of an equal number: CAAC8-11 + LC, LC control and blank control, the former given CAAC8-11 in addition to LC oral liquid, and the latter two given LC oral liquid and life intervention, respectively, all for 12 weeks. We collected semen samples from all the patients before and after treatment, and examined perm motility, the contents of neutral α- glucosidase (NAG) and reactive oxygen species (ROS), sperm DNA fragmentation index (DFI), and the expression of the Nrf2 protein. RESULTS: Compared with the baseline, the total sperm motility was significantly improved in the IAS patients after treated with CAAC8-11 + LC (ï¼»27.50 ± 0.77ï¼½% vs ï¼»32.50 ± 0.74ï¼½%, P < 0.05) or LC only (ï¼»27.60 ± 0.66ï¼½% vs ï¼»30.90 ± 0.70ï¼½%, P < 0.05), dramatically higher in the CAAC8-11 + LC than in the LC and blank control groups (P < 0.01). The content of NAG in the epididymis was remarkably increased after treatment in the CAAC8-11 + LC than in the LC and blank control groups (ï¼»23.90 ± 0.56ï¼½ vs ï¼»21.20 ± 0.49ï¼½ and ï¼»16.80 ± 0.42ï¼½ mU, P < 0.05), so was the expression of Nrf2 (P < 0.05), while the ROS level was markedly decreased in the former than in the latter two groups (ï¼»81.60 ± 2.50ï¼½ vs ï¼»88.50 ± 2.50ï¼½ and ï¼»88.70 ± 2.40ï¼½ µg/ml, P < 0.05). CONCLUSION: CAAC8-11 + LC has a good clinical effect on asthenospermia, with no adverse reactions, which may be attributed to its ability to regulate the high expression of Nrf2, decrease the production of ROS and reduce the damage of oxidative stress to sperm motility.

Genomic Analysis of Clostridioides difficile in 2 Regions of the United States Reveals a Diversity of Strains and Limited Transmission.

BACKGROUND: The distribution of Clostridioides difficile strains and transmission dynamics in the United States are not well defined. Whole-genome sequencing across 2 Centers for Disease Control and Prevention Emerging Infections Program C. difficile infection (CDI) surveillance regions (Minnesota and New York) was performed to identify predominant multilocus sequence types (MLSTs) in community-associated (CA) and healthcare-associated (HCA) disease and assess transmission. METHODS: Whole-genome sequencing was performed on C. difficile isolates from patients with CDI over 3 months between 2016 and 2017. Patients were residents of the catchment area without a positive C. difficile test in the preceding 8 weeks. CDI cases were epidemiologically classified as HCA or CA. RESULTS: Of 422 isolates, 212 (50.2%) were HCA and 203 (48.1%) were CA. Predominant MLSTs were sequence type (ST) 42 (9.3%), ST8 (7.8%), and ST2 (8.1%). MLSTs associated with HCA-CDI included ST1 (76%), ST53 (83.3%), and ST43 (80.0%), while those associated with CA-CDI included ST3 (76.9%) and ST41 (77.8%). ST1 was more frequent in New York than in Minnesota (10.8% vs 3.1%). Thirty-three pairs were closely related genomically, 14 of which had potential patient-to-patient transmission supported by record review. CONCLUSIONS: The genomic epidemiology of C. difficile across 2 regions of the United States indicates the presence of a diverse strain profile and limited direct transmission.