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Introduction Metritis is a common postpartum disease in dairy cows. As a mast cell (MC) mediator, leukotriene B4 (LTB4) is the strongest phagocyte chemokine. It is important in inflammation for the recruitment of immune cells to resist infection. This study investigated the effect of LTB4 in metritis. Material and Methods Twenty Holstein cows 3 to 6 years old and at 6 to 10 days postpartum were selected, ten of which with postpartum metritis were the experimental group, and the other ten of which as healthy cows were the control group. The levels of LTB4, substance P (SP) and vasoactive intestinal peptide (VIP) were measured by ELISA, the expression of LTB4 receptor 2 (BLT2), matrix metalloproteinase (MMP)-2 and MMP-9 mRNA was measured by qPCR, and collagens I and IV were detected by immunohistochemical staining. Results Concentrations of SP and LTB4 were significantly higher, but those of VIP were significantly lower in the experimental group than those in the control group. The expression of BLT2, MMP-2 and MMP-9 mRNA was significantly higher in the experimental group than that in the control group. The expression of collagen Ⅰ and collagen Ⅳ was significantly lower in the experimental group than that in the control group. Conclusion In metritis, SP promotes the activation of MC and the synthesis and release of LTB4. Leukotriene B4 chemotactic immune cells promote the high expression of collagenase, which accelerated the hydrolysis of collagen, while the inhibitory effect of VIP on MC was weakened. This may further aggravate the damage to uterine tissue.

Aldehydes as an environmental pollutant may lead to oxidative stress, which is an important mechanism in the development of osteoporosis. This suggests a possible link between aldehyde exposure and osteoporosis. Considering the mixed nature of aldehyde exposure and the interactions between different aldehydes, we explored for the first time the associations between mixed six aldehydes (benzaldehyde, butyraldehyde, heptanal, hexanal, isovaleraldehyde, and propionaldehyde) and BMD in three populations (men, premenopausal women, and postmenopausal women) by applying four statistical models: quantile g-computation (qgcomp) model, Bayesian kernel machine regression (BKMR) model, generalized linear regression model (GLM), and generalized additive model (GAM), based on the National Health and Nutrition Examination Survey (NHANES) 2013-2014. We found that mixed aldehydes could significantly reduce BMD in men, with hexanaldehyde and propanaldehyde having the greatest negative qgcomp model and BKMR model weights, also confirmed by GLM. The associations between isopentanaldehyde and propanaldehyde and femoral BMD in men were non-linear and had threshold effects as derived from the BKMR model and GAM. The associations turned positive when the concentrations of isopentanaldehyde and propanaldehyde exceeded their respective inflection points. To conclude, our study might provide new ideas for the prevention and treatment of osteoporosis, and hexanaldehyde and propanaldehyde should be more regulated to prevent osteoporosis.

The hydrological process in the dry–warm valley of the mountainous area of southwestern China has unique characteristics and has attracted scientific attention worldwide. Given that this is an area with fragile ecosystems and intensive water resource conflicts in the upper reaches of the Yangtze River, a systematic identification of its hydrological responses to climate and land use variations needs to be performed. In this study, MIKE SHE was employed and calibrated for the Anning River Basin in the dry–warm valley. Subsequently, a deep learning neural network model of the long short-term memory (LSTM) and a traditional multi-model ensemble mean (MMEM) method were used for an ensemble of 31 global climate models (GCMs) for climate projection. The cellular automata–Markov model was implemented to project the spatial pattern of land use considering climatic, social, and economic conditions. Four sets of climate projections and three sets of land use projections were generated and fed into the MIKE SHE to project hydrologic responses from 2021 to 2050. For the calibration and first validation periods of the daily simulation, the coefficients of determination (R) were 0.85 and 0.87 and the Nash–Sutcliffe efficiency values were 0.72 and 0.73, respectively. The advanced LSTM performed better than the traditional MMEM method for daily temperature and monthly precipitation. The average monthly temperature projection under representative concentration pathway 8.5 (RCP8.5) was expected to be slightly higher than that under RCP4.5; this is contrary to the average monthly precipitation from June to October. The variations in streamflow and actual evapotranspiration (ET) were both more sensitive to climate change than to land use change. There was no significant relationship between the variations in streamflow and the ET in the study area. This work could provide general variation conditions and a range of hydrologic responses to complex and changing environments, thereby assisting with stochastic uncertainty and optimizing water resource management in critical regions.

In situ mineralized PLGA/PSBMA scaffold enables high-efficiency sustained release of rhBMP-2 (only 1.7% within 35 days) and robust healing of critical-sized (5 mm) nonunion calvarial defects in rats with an ultralow dosage of rhBMP-2 (150 ng per scaffold).

Designing non-noble metal electrocatalysts toward alkaline hydrogen evolution reaction (HER) with high performance at a large current density is urgent. Herein, a CoO/CoP heterostructure catalyst (termed POZ) was designed by a phosphating strategy. The strong electron transfer on the interface of CoO/CoP was experimentally and theoretically proven. POZ showed a low overpotential of 236 mV at 400 mA/cm2, which was 249 mV lower than non-phosphated sample. It also exhibited a remarkable solar-to-hydrogen conversion efficiency of 10.5%. In this work, the construction of CoO/CoP interface realized by a simple phosphating strategy could provide an important reference to boost the HER performance on those materials not merely metal oxides.

This study examines the impact of SEC enforcement actions on the turnovers of culpable CEOs and CFOs named in the enforcement actions, following their violations of the SOX provisions. We compare the impact on CEO turnover with that on CFO turnover. The impact in the pre-SOX period and that in the post-SOX period are also compared. Findings of this study provide evidence that the SEC enforcement actions are associated with the probabilities of turnovers of CEOs and CFOs named in the SEC enforcement actions for violations of SOX 303 and SOX 305. Specifically, CEOs sanctioned by the SEC are likely to lose their positions when they violate SOX 305. In contrast, CFOs sanctioned by the SEC for violating SOX 303 are likely to be forced to resign. When CFOs are named as mastermind by the SEC, they are likely to lose jobs. However, when both CEO and CFO are named as masterminds in fraudulent financial reporting, CFOs are less likely to be removed. In addition, CEOs and CFOs are likely to lose their jobs when firms face bankruptcy and restate earnings and when they face criminal charges, especially in the post-SOX period.

Durability is crucial for the long-term application of cathode oxygen reduction reaction (ORR) catalysts in fuel cells. In this work, sulfur was successfully doped into reduced graphene oxide aerogels to achieve the formation of 1T/2H hybrid phase MoS2, obtaining MoS2@S-rGO-300 composite ORR catalyst support. After loading ultrafine Pt nanoparticles, Pt/MoS2@S-rGO-300 shows not only an enhanced ORR activity, but also a significantly improved stability after 10,000 cycles. The mass activity retention for Pt/MoS2@S-rGO-300 after cycles reaches 89.94%, while that of Pt/rGO is only 37.44%. Density functional theory calculations reveal that the enlarged binding energy between Pt atoms and MoS2@S-rGO-300 leads to the prevention of Pt agglomeration as well as Ostwald ripening.

The neuroendocrine system consists of a heterogeneous collection of neuropeptidergic neurons in the brain, among which hypothalamic KNDy neurons represent an indispensable cell subtype controlling puberty onset. Although neural progenitors and neuronal precursors along the cell lineage hierarchy adopt a cascade diversification strategy to generate hypothalamic neuronal heterogeneity, the cellular logic operating within the lineage to specify a subtype of neuroendocrine neurons remains unclear. As human genetic studies have recently established a link between TBX3 mutations and delayed puberty onset, we systematically studied Tbx3-derived neuronal lineage and Tbx3-dependent neuronal specification and found that Tbx3 hierarchically established and maintained the identity of KNDy neurons for triggering puberty. Apart from the well-established lineage-dependent fate determination, we uncovered rules of interlineage interaction and intralineage retention operating through neuronal differentiation in the absence of Tbx3. Moreover, we revealed that human TBX3 mutations disturbed the phase separation of encoded proteins and impaired transcriptional regulation of key neuropeptides, providing a pathological mechanism underlying TBX3-associated puberty disorders.

Primary aldosteronism (PA) is a disease characterized by hypertension and hypokalemia due to the excessive aldosterone secretion from the adrenal cortex, which leads to the retention of both water and sodium, and the inhibition of the renin-angiotensin system as well. Familial hyperaldosteronism type II (FH-II) is known as an autosomal dominant hereditary disease, which is a scarce cause of PA. In this report, we cllected the clinical data of a patient with repeated hypertension and hypokalemia of uncertain diagnosis since 2014. Nevertheless, we discovered by genetic sequencing in 2021 that the CLCN2 and WFS1 gene mutation of the patient, whose mother belongs to heterozygote genotype and father belongs to wild-type genotype. Combined with a series of endocrine function tests and imaging studies, the patient was finally certified her suffering from FH-II and WFS1 gene mutation. By summarizing and analyzing the characteristics and genetic test results of this case, we recommended gene sequencing for patients with PA whose etiology is difficult to be determined clinically. This case also provides new clinical data for subsequent genetic studies of the disease.原发性醛固酮增多症(primary aldosteronism, PA)又简称原醛症，是指肾上腺皮质分泌过量醛固酮(aldosterone，ALD)，导致水钠潴留及肾素-血管紧张素系统受抑制，从而引起高血压、低血钾的一类疾病。家族性醛固酮增多症II型(familial hyperaldosteronism type II, FH-II)是PA的少见病因，为常染色体显性遗传病。本文收集1例自2014年起病以来反复高血压、低血钾的病例，该患者诊断结果一直未明确。2021年通过基因检测证实该患者存在CLCN2及WFS1基因突变，其母亲为杂合携带，父亲为野生型。结合内分泌功能试验结果及影像学资料，考虑患者为FH-II，同时合并WFS1基因突变。通过总结分析该病例特点及基因检测结果，对于临床难以明确病因的PA建议可行基因测序。该病例也为后续遗传学研究提供临床资料。.

Recent advances in bioengineering and manufacturing have catapulted Antibody–drug conjugates (ADCs) to broader clinical applications. ADCs take advantage of the exquisite specificity of monoclonal antibodies (mAb) to deliver a highly potent cytotoxic agent to a specifically targeted cell expressing a selected antigen. HER2-positive breast cancer has served as a testing ground for ADC development in solid tumors that over-express HER2/neu by linking trastuzumab to a payload agent. With the current advances, ADCs leverage the selective targeting of monoclonal antibodies to deliver highly potent agents which otherwise have a narrow therapeutic index. Ado-trastuzumab emtansine (T-DM1) was the first ADC approved for patients with HER2-postive metastatic breast cancer (MBC) and fam-trastuzumab deruxtecan-nxki (T-DXd) was recently approved as well. Sacituzumab govitecan-hziy (SG) was approved in 2020 for patients with triple negative breast cancer (TNBC). Studies focusing on utilizing ADCs in earlier stages of breast cancer in the neoadjuvant or adjuvant setting, and central nervous system (CNS) disease are in progress. New ADCs and bispecific antibodies (bAbs) are also in development.

Gonadotropin-releasing hormone (GnRH), a decapeptide secreted by hypothalamic neurons, is a key signalling molecule of the hypothalamic–pituitary–gonadal axis for the control of reproduction in ver...

Phenols and parabens widely exist in personal care and consumer products and have been proved to be endocrine disrupting chemicals that could disturb bone metabolism. The current studies focusing on the associations between phenols and parabens with bone mineral density (BMD) drew contradictory conclusions. Considering the bias might be due to not considering the effects of mixed exposure, we conducted the first cross-sectional study to investigate the associations of both single and mixed metabolites of phenols and parabens with BMD in three populations by setting up four models: generalized linear regression model (GLM), weighted quantile sum (WQS) regression model, quantile g-computation (qgcomp) model and Bayesian kernel machine regression (BKMR) model, based on the US National Health and Nutrition Examination Survey (NHANES) database. We found that the association between the mixtures and total femur BMD in men was significantly negative. Bisphenol A (BPA) was shown to play the most important role in this negative association in the BKMR model, and this negative association was also confirmed in the GLM model with β coefficient (95% CI) being -0.02 (-0.04, -0.01). The relationships between the mixtures and femoral neck and trochanter BMD in postmenopausal women were significantly positive. Benzophenone-3 (BP-3) played the most significant role in the positive association with trochanter BMD, as confirmed by the WQS, qgcomp and BKMR models, and this positive association was also verified by the GLM model with β coefficient (95% CI) being 0.01 (0.00, 0.02). In conclusion, the association between the mixed phenols and parabens and BMD was negative in men while was positive in postmenopausal women, which was gender-specific. This study might provide new ideas for the prevention and treatment of osteoporosis and the control of personal care and consumer products containing phenols and parabens in the future.

Objective Sarcopenic obesity is a prevalent geriatric syndrome, characterized by concurrence of sarcopenia and obesity. Sleep duration is linked to both obesity and sarcopenia. However, little was known regarding the association of sleep duration with sarcopenic obesity. In this study, we aimed to examine the association of sleep duration with sarcopenic obesity in multi-ethnic community-dwelling older adults. Methods Sarcopenia was defined according to the criteria established by Asian Working Group for Sarcopenia (AWGS) 2019. Obesity was defined as body fat percentage above the 60th percentile specified by sex. Sarcopenic obesity was defined as concurrence of obesity and sarcopenia. Sleep duration was collected by a self-reported questionnaire and was further divided into 5 groups: “ Results 2256 multi-ethnic adults aged 60 and over from the West China Health and Aging Trend (WCHAT) study were involved for present study. Overall, 6.25% of the participants were classified as sarcopenic obesity. In the fully adjusted model, long sleep duration (≥ 9 h) was significantly associated with sarcopenic obesity compared with reference group (OR = 1.81, 95%CI = 1.10–2.98, P = 0.019). However, in subgroup analysis, this association can only be observed in male (OR 1.98, 95% CI = 1.02–3.87, P = 0.043) not in female (OR = 1.83, 95%CI = 0.85–3.94, P = 0.118). Regarding ethnic difference, Han older adults with long sleep duration (≥ 9 h) presented increased risk of sarcopenic obesity while ethnic minorities did not. Conclusion This study disclosed that long sleep duration significantly increased the risk of sarcopenic obesity among older adults. And our findings highlight the critical role of assessing sleep duration to identify individuals at risk of sarcopenic obesity.

Traditional blue water resources assessment and management may not meet the needs of sustainable water resource utilization; ignoring the number of green water resources will underestimate the availability of water resources. To rationally allocate and scientifically manage the limited water resources, it is necessary to divide the rich and poor flow situation of blue water and green water. The MIKE SHE-MIKE HYDRO integrated coupled model was selected and used in the Yalong River basin to ascertain the blue and green water in the hydrological cycle. The model was calibrated by matching simulated discharge against observed streamflow discharge at the Tongziling Station. At the same time, the research analyzed the component of green water and the total amount of blue water or green water on a temporal scale. The set pair analysis (SPA) was introduced to classify blue water and green water, which can not only understand the amount and distribution characteristics of water resources in the Yalong River Basin but also rationally allocate the total of water resources in the basin from the perspective of the regional water cycle. Furthermore, according to the situation of blue water and green water in the basin, the related policies are formulated to realize the efficient utilization of water resources in the Yalong River basin.

Pulmonary toxicity is dose-limiting in stereotactic body radiation therapy (SBRT) for tumors that abut the proximal bronchial tree (PBT), esophagus, or other mediastinal structures. In this work we explored published models of pulmonary toxicity following SBRT for such ultracentral tumors in an independent cohort of patients.The PubMed database was searched for pulmonary toxicity models. Identified models were tested in a cohort of patients with ultracentral lung tumors treated between 2008 and 2017 at one large center (N = 88). This cohort included 60 % primary and 40 % metastatic tumors treated to 45 Gy in 5 fractions (fx), 50 Gy in 5 fx, 60 Gy in 8 fx, or 60 Gy in 15 fx prescribed as 100 % dose to PTV.Seven published NTCP models from two studies were identified. The NTCP models utilized PBT max point dose (Dmax), D0.2 cmPulmonary toxicity models were identified from two studies and explored within an independent ultracentral lung tumor cohort. A modified Dmax to 0.1 cm

Photoreduction of CO

A high-temperature proton exchange membrane was fabricated based on polyvinylidene fluoride (PVDF) and polyvinylpyrrolidone (PVP) blend polymer nanofibers. Using electrospinning method, abundant small ionic clusters can be formed and agglomerated on membrane surface, which would facilitate the proton conductivity. To further enhance the conductivity, phosphoric acid (PA) retention as well as mechanical strength, sulfamic acid (SA)-doped metal–organic framework MIL-101 was incorporated into PVP-PVDF blend nanofiber membranes. As a result, the anhydrous proton conductivity of the composite SA/MIL101@PVP-PVDF membrane reached 0.237 S cm−1 at 160 °C at a moderate acid doping level (ADL) of 12.7. The construction of long-range conducting network by electrospinning method combined with hot-pressing and the synergistic effect between PVP-PVDF, SA/MIL-101 and PA all contribute to the proton conducting behaviors of this composite membrane.

Background The coronavirus disease 2019 (COVID-19) outbreak has brought great challenges to public health. Aggravation of COVID-19 is closely related to the secondary systemic inflammatory response. Glucocorticoids are used to control severe diseases caused by the cytokine storm, owing to their anti-inflammatory effects. However, glucocorticoids are a double-edged sword, as the use of large doses has the potential risk of secondary infection and long-term serious complications, and may prolong virus clearance time. Nonetheless, the risks and benefits of glucocorticoid adjuvant therapy for COVID-19 are inconclusive. Aim To determine the effect of methylprednisolone in severe and critically ill patients with COVID-19. Methods This single-center retrospective study included 102 adult COVID-19 patients admitted to a ward of a designated hospital in Wuhan, Hubei Province from January to March 2020. All patients received general symptomatic treatment and organ function support, and were given different respiratory support measures according to their conditions. In case of deterioration, considering the hyperinflammatory state of the patients, methylprednisolone was intravenously administered at 0.75-1.5 mg/kg/d, usually for less than 14 d. Patient vital signs and oxygenation were closely monitored, in combination with imaging and routine blood tests such as C-reactive protein, biochemical indicators (liver and kidney function, myocardial enzymes, electrolytes, etc.), and coagulation function. Patient clinical outcomes were discharge or death. Results A total of 102 severe and critically ill COVID-19 patients were included in this study. They were divided into treatment (69, 67.6%) and control groups (33, 32.4%) according to methylprednisolone use. Comparison of baseline data between the two groups showed that the treatment group patients had higher aspartic acid aminotransferase, globulin, hydroxybutyrate dehydrogenase, and lactate dehydrogenase. There was no significant difference in other baseline data between the two groups. With regard to prognosis, 29 (78.4%) patients in the treatment group died as opposed to 40 (61.5%) in the control group. The mortality was higher in the treatment group than in the control group; however, according to the log-rank test and the Kaplan-Meier survival curve, the difference in mortality between both groups was insignificant (P = 0.655). The COX regression equation was used to correct the variables with differences, and the results showed that methylprednisolone treatment did not improve prognosis. Conclusion Methylprednisolone treatment does not improve prognosis in severe and critical COVID-19 patients.

5-hydroxytryptamine receptor 5B (5-HT5B) is a gene coding for a G protein-coupled receptor (GPCR) that plays key roles in several neurodevelopmental disorders. Our previous study showed that disruption of 5-HT5B induced by lysine (K)-specific demethylase 6A (Kdm6a, also known as Utx) conditional knockout (cKO) in mouse hippocampus was associated with cognition deficits underlying intellectual disability in Kabuki syndrome (KS), a rare disease associated with multiple congenital and developmental abnormalities, especially neurobehavioral features. Here we show that Utx knockout (KO) in cultured hippocampal neurons leads to impaired neuronal excitability and calcium homeostasis. In addition, we show that 5-HT5B overexpression reverses dysregulation of neuronal excitability, intracellular calcium homeostasis, and long-term potentiation (LTP) in cultured Utx KO hippocampal neurons and hippocampal slices. More importantly, overexpression of 5-HT5B in Utx cKO mice results in reversal of abnormal anxiety-like behaviors and impaired spatial memory ability. Our findings therefore indicate that 5-HT5B, as a downstream target of Utx, functions to modulate electrophysiological outcomes, thereby affecting behavioral activities in KS mouse models.

Organisms produce high levels of reactive oxygen species (ROS) to kill pathogens or act as signaling molecules to induce immune responses; however, excessive ROS can result in cell death. To maintain ROS balance and cell survival, mitophagy selectively eliminates damaged mitochondria via mitophagy receptors in vertebrates. In marine invertebrates, however, mitophagy and its functions remain largely unknown. In the current study,机体产生高水平的活性氧可以直接杀死病原体或作为信号分子诱导免疫反应发生，然而过量的活性氧会导致细胞死亡。为了维持活性氧平衡和细胞存活，脊椎动物通过线粒体自噬受体激活线粒体自噬以选择性地清除破损的线粒体。然而，在海洋无脊椎动物中，线粒体自噬及其功能在很大程度上是未知的。在该研究中，我们发现灿烂弧菌感染会破坏刺参（

NH3 is a type of essential raw material but harmful. In this work, CeO2 nanoparticles were synthesized as NH3 gas sensing materials by simple hydrothermal method. The response time of the sensor is extremely fast (3 s) towards 500 ppm NH3 with the response of 22.0 at room temperature. The concentration of NH3 and its response show well-matched functional relationship in the range of 0.5 ppm-1000 ppm. The selectivity of NH3 is distinct and the detection limit is as low as 500 ppb. The excellent NH3 gas sensing performance may be attributed to more oxygen vacancies and narrower band gap. This CeO2 nanoparticles-based gas sensor could be reliable to detect and monitor NH3 at room temperature.

Designing a novel heterojunction structure on a SiC gas sensing material is extremely desirable for high-performance gas sensors applied in harsh environments. Inspired by the unprecedented catalyzing effect of single-atom catalysts, here, we have sequentially loaded tin oxide nanorods (SnO2 NRs) and platinum single atoms (Pt SAs) on silicon carbide nanosheets (SiC NSs) to build a novel Pt SAs@SnO2 NRs@SiC NSs multi-heterojunction. Gas sensors based on Pt SAs@SnO2 NRs@SiC NSs show highly enhanced gas sensing performance, including high response (119.75 ± 3.90), ppb level detecting, short response/recovery time (∼14 and ∼ 20 s), good selectivity, and excellent stability under high temperature. Particularly, the Pt SAs@SnO2 NRs@SiC NSs gas sensor has a response larger than 30 even under 500 °C and possesses good long-term stability. Such improvement of sensing performance can be attributed to the catalyzing effect of Pt single atoms, band gap tuning of the SnO2 nanostructure, promoted electron transfer of SnO2@SiC, and high surface area of two-dimensional (2D) SiC nanosheets. This approach enlightens the perspective application of single-atom catalysts, small-size effect of SnO2 nanorods, and 2D nanostructure on gas sensing fields and provides new routes for designing new types of gas sensing materials.