Hypidone hydrochloride(YL-0919)ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation

Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.

Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

Asymmetric expression of CA2 and CA13 linked to calcification in the bilateral mandibular condyles cause crossed beaks in chickens

Crossed beak is a complex mode of inheritance with prevalence ranging from 0.2 to 7.4% in at least 12 chicken strains worldwide.To reveal the intrinsic factors causing crossed beaks,genes expression patterns in bilateral mandibular condyle between affected and normal birds were characterized by RNA sequencing analysis in the present studies.Crossed beak was induced by short length of unilateral mandibular ramus,and a total of 110differentially expressed genes were up-or down-regulated in the affected(short)mandibular condyle side as compared to the normal side.Carbonic anhydrase 2(CA2)and Carbonic anhydrase 13(CA13)were enriched in the carbonate dehydratase activity,and high-expressed in mandibular condyle and osteoblasts(P<0.05).However,both were low-expressed in short mandibular condyle side of affected birds(P<0.05).The carbonate dehydratase inhibitor experiments confirmed that there is positive association between the calcification and carbonic anhydrase isoenzymes.Quantitative analysis with cetylpyridinium chloride showed a decrease in calcification when the cells were transfected with an anti-CA13 shRNA.Our research suggested that CA2 and CA13 are down-calcified in shortside mandibular condyle,and caused mandibular ramus to grow slowly.CA2 and CA13 have the critical role in crossed beaks by regulating calcification of mandibular condyle.

Homozygous CCDC146 mutation causes oligoasthenoteratozoospermia in humans and mice

Infertility represents a significant health concern,with sperm quantity and quality being crucial determinants of male fertility.Oligoasthenoteratozoospermia(OAT)is characterized by reduced sperm motility,lower sperm concentration,and morphological abnormalities in sperm heads and flagella.Although variants in several genes have been implicated in OAT,its genetic etiologies and pathogenetic mechanisms remain inadequately understood.In this study,we identified a homozygous nonsense mutation(c.916C>T,p.Arg306*)in the coiled-coil domain containing 146(CCDC146)gene in an infertile male patient with OAT.This mutation resulted in the production of a truncated CCDC146 protein(amino acids 1-305),retaining only two out of five coiled-coil domains.To validate the pathogenicity of the CCDC146 mutation,we generated a mouse model(Ccdc146^(mut/mut))with a similar mutation to that of the patient.Consistently,the Ccdc146mut/mut mice exhibited infertility,characterized by significantly reduced sperm counts,diminished motility,and multiple defects in sperm heads and flagella.Furthermore,the levels of axonemal proteins,including DNAH17,DNAH1,and SPAG6,were significantly reduced in the sperm of Ccdc146^(mut/mut) mice.Additionally,both human and mouse CCDC146 interacted with intraflagellar transport protein 20(IFT20),but this interaction was lost in the mutated versions,leading to the degradation of IFT20.This study identified a novel deleterious homozygous nonsense mutation in CCDC146 that causes male infertility,potentially by disrupting axonemal protein transportation.These findings offer valuable insights for genetic counseling and understanding the mechanisms underlying CCDC146 mutant-associated infertility in human males.

Image segmentation of exfoliated two-dimensional materials by generative adversarial network-based data augmentation

Mechanically cleaved two-dimensional materials are random in size and thickness.Recognizing atomically thin flakes by human experts is inefficient and unsuitable for scalable production.Deep learning algorithms have been adopted as an alternative,nevertheless a major challenge is a lack of sufficient actual training images.Here we report the generation of synthetic two-dimensional materials images using StyleGAN3 to complement the dataset.DeepLabv3Plus network is trained with the synthetic images which reduces overfitting and improves recognition accuracy to over 90%.A semi-supervisory technique for labeling images is introduced to reduce manual efforts.The sharper edges recognized by this method facilitate material stacking with precise edge alignment,which benefits exploring novel properties of layered-material devices that crucially depend on the interlayer twist-angle.This feasible and efficient method allows for the rapid and high-quality manufacturing of atomically thin materials and devices.

A Study of In-Hospital Charitable Aid Resource Categories and Application Dilemmas: An Empirical Investigation Based on R Hospital

To better understand the challenges faced by public hospitals in implementing charitable medical assistance,this study examines Nanjing R Hospital as a case study.By combining literature review and field research,the current status and fundamental methods of charitable medical assistance at R Hospital are systematically analyzed.The findings indicate that medical social workers play a multifaceted role in the hospital’s charitable assistance efforts.They contribute significantly to building assistance networks and addressing patients’multi-dimensional needs.However,challenges persist in the assistance process,including both external and internal obstacles.This study explores ways to overcome these barriers to enhance the efficient utilization of healthcare resources.Through empirical investigation,the study identifies the types of charitable aid resources available and highlights the practical difficulties in their application within public hospitals.These findings provide a valuable reference for optimizing resource allocation,improving the effectiveness of assistance programs,and fostering institutional collaboration.

Monochromatic green light stimulation during incubation shortened the hatching time via pineal function in White Leghorn eggs

Background:Effect of monochromatic green light illumination on embryo development has been reported in chickens.The avian pineal gland is an important photo-endocrine organ formed by a mediodorsal protrusion during embryonic development.However,the involvement of pineal gland in the light transduction process remains to be elucidated.In the present study,we investigated the influence of monochromatic green light on hatching time and explored the possible mechanism via pineal function.Results:A total of 600 eggs of White Leghorn(Shaver strain)were incubated under photoperiods of either 12 h of light and 12 h of darkness using monochromatic green light(12L:12D group)or 24 h of darkness(0L:24D group)for 18 d.Compared to 0L:24D group,the green light stimulation shortened the hatching time without extending the hatch window or impairing hatchability.The liver of embryos incubated in the 12L:12D light condition was heavier than those of the 0L:24D group on d 21 post incubation which may be linked to the observed increase in the serum concentration of insulin-like growth factor 1(IGF-1);primary secretion of the liver.Histological structure analysis of pineal gland demonstrated that the light stimulation increased follicle area,wall thickness and lumen area on d 10 and d 12 post incubation.Rhythmic function analysis demonstrated that three clock related genes(brain and muscle ARNT-like-1,BMAL1;circadian locomotor output cycles kaput,CLOCK;and cryptochrome-1,CRY1)and a melatonin rate-limiting enzyme related gene(arylalkylamine N-acetyltransferase,AANAT)were rhythmically expressed in the pineal gland of the 12L:12D group,but not in the 0L:24D group.Simultaneously,the light stimulation also increased the concentration of melatonin(MT),which was linked to hepatocyte proliferation and IGF-1 secretion in previous studies.Conclusions:The 12L:12D monochromatic green light stimulation during incubation shortened hatching time without impairing hatching performance.Pineal gland’s early histological development and maturation of its rhythmic function were accelerated by the light stimulation.It may be the key organ in the photo-endocrine axis that regulates embryo development,and the potential mechanism could be through enhanced secretion of MT in the 12L:12D group which promotes the secretion of IGF-1.

Human-in-the-Loop Consensus Control for Nonlinear Multi-Agent Systems With Actuator Faults

This paper considers the human-in-the-loop leader-following consensus control problem of multi-agent systems(MASs)with unknown matched nonlinear functions and actuator faults.It is assumed that a human operator controls the MASs via sending the command signal to a non-autonomous leader which generates the desired trajectory.Moreover,the leader’s input is nonzero and not available to all followers.By using neural networks and fault estimators to approximate unknown nonlinear dynamics and identify the actuator faults,respectively,the neighborhood observer-based neural fault-tolerant controller with dynamic coupling gains is designed.It is proved that the state of each follower can synchronize with the leader’s state under a directed graph and all signals in the closed-loop system are guaranteed to be cooperatively uniformly ultimately bounded.Finally,simulation results are presented for verifying the effectiveness of the proposed control method.

Adaptive Fixed-Time Control of Nonlinear MASs With Actuator Faults

The adaptive fixed-time consensus problem for a class of nonlinear multi-agent systems(MASs)with actuator faults is considered in this paper.To approximate the unknown nonlinear functions in MASs,radial basis function neural networks are used.In addition,the first order sliding mode differentiator is utilized to solve the“explosion of complexity”problem,and a filter error compensation method is proposed to ensure the convergence of filter error in fixed time.With the help of the Nussbaum function,the actuator failure compensation mechanism is constructed.By designing the adaptive fixed-time controller,all signals in MASs are bounded,and the consensus errors between the leader and all followers converge to a small area of origin.Finally,the effectiveness of the proposed control method is verified by simulation examples.

Tea polyphenol-gut microbiota interactions:hints on improving the metabolic syndrome in a multi-element and multi-target manner

The metabolic syndrome(MS)has become one of the main problems in public health.Tea polyphenols(TPs),the main bioactive components of tea,has been claimed to have the potential to regulate metabolism and effectively prevent or mitigate the MS.However,many studies into the effects of TPs on MS have provided conflicting findings and the underlying mechanism has been elusive.The predominant TPs in unfermentedand and fermented tea are catechins and oxidized polyphenols(theaflavins and thearubigins),both of which have low bioavailability and reach the colon where most gut microbes inhabit.Gut microbiota has been demonstrated to be tightly associated with host metabolism.The interactions between TPs and gut microbiota will lead to the alterations of gut microbiota composition and the production of metabolites including short chain fatty acids,bile acids,amino acids and TPs derived metabolites,accordingly exerting their biological effects both locally and systemically.This review highlighted the contribution of metabolites and specific gut bacteria in the process of TPs intervention on the MS and further discuss how TPs impact the MS via gut microbiota from the viewpoint of gut organ/tissue axis.

CHARACTERISTIC FEATURES OF MUELLER MATRIX PATTERNS FOR POLARIZATION SCATTERING MODEL OF BIOLOGICAL TISSUES

We developed a model to describe polarized photon scattering in biological tissues.In this model,tissues are simplified to a mixture of scatterers and surrounding mpdium.There are t wo types ofscatterers in the model:solid spheres and infinitely long solid cylinders.Variables related to thescatterers include:the densities and sizes of the spheres and cylinders,the orientation and angulardistribution of cylinders.Variables related to the surrounding medium include:the refractiveindex,absorption coeficient and birefringence.In this paper,as a development we introduce anoptical activity effct to the model.By comparing experiments and Monte Carlo simulations,we analyze the backscater ing Mueller matrix patterms of several tissue-like media,and summarizethe different effects coming from anisotropic scattering and optical properties.In addition,wepropose a possible method to extract the optical activity values for tissues.Both the experimentaland simulated results show that,by analyzing the Mueller matrix patterns,the microstructureand optical properties of the medium can be obtained.The characteristic features of Muellermatrix patterns are potentilly powerful tools for studying the contrast mechanisms of polari-zation imaging for medical diagnosis.

Computationally predicted pathogenic USP9X mutation identified in infertile men does not affect spermatogenesis in mice

Infertility is a major health issue,affecting approximately 15%of couples of child-bearing age.Although nearly half of idiopathic infertility cases are assumed to have a genetic basis,the underlying causes remain largely unknown in most infertile men.

Development of a psychosocial functioning questionnaire for patients with major depressive disorder

Background The importance of psychosocial functioning in the assessment,diagnosis and treatment of major depressive disorder(MDD)is widely recognised.However,there is a lack of effective scales to assess psychosocial functioning in patients with MDD.Aims To develop a professional questionnaire to evaluate the psychosocial functioning of patients with MDD.Methods Using a literature review,an open-ended questionnaire survey,and patient interviews,a theoretical model of psychosocial functioning was constructed,and an initial questionnaire was formed which included four dimensions.After two rounds of testing,using items analysis and exploratory factor analysis,a finalized questionnaire was created.There were 460 patients with MDD selected from six psychiatric hospitals for formal testing using a convenience sampling method.Forty patients were randomly selected and retested one week later to evaluate the test-retest reliability of the scale.The Patient Health Questionnaire-9(PHQ-9),Short Form of Quality of Life Enjoyment and Satisfaction Questionnaire(Q-LES Q SF),Sheehan Disability Scale(SDS),and Dysfunctional Attitudes Scale(DAS)provided major standards to check the criterion validity of this questionnaire.Correlation analysis,confirmatory factor analysis,and internal consistency reliability testing were used to examine other psychometric characteristics of the finalized questionnaire.Results The Psychosocial Functioning Questionnaire(PFQ)for patients with MDD included three dimensions:psychological cognitive functioning,subjective well-being,and social functioning,with a total of 18 items.The overall internal consistency reliability of the questionnaire was 0.957,and the test-retest reliability was 0.840.Confirmatory factor analysis showed that the model fitted well:Goodness of Fit Index(GFI)=0.888;Root Mean SquareError of Approximation(RMSEA)=0.085.The total score of PFQ was significantly correlated with the total score of PHQ-9,DAS,SDS and Q-LES Q SF(|r|=0.599-0.870,p<0.001).Conclusions The Psychosocial Functioning Questionnaire has good reliability and validity.It can be used to measure the psychosocial functioning of patients with MDD.

Polarimetry feature parameter deriving from Mueller matrix imaging and auto-diagnostic signicance to distinguish HSIL and CSCC

High-grade squamous intraepithelial lesion(HSIL)is regarded as a serious precancerous state of cervix,and it is easy to progress into cervical invasive carcinoma which highlights the importance of earlier diagnosis and treatment of cervical lesions.Pathologists examine the biopsied cervical epithelial tissue through a microscope.The pathological examination will take a long time and sometimes results in high inter-and intra-observer variability in outcomes.Polarization imaging techniques have broad application prospects for biomedical diagnosis such as breast,liver,colon,thyroid and so on.In our team,we have derived polarimetry feature parameters(PFPs)to characterize microstructural features in histological sections of breast tissues,and the accuracy for PFPs ranges from 0.82 to 0.91.Therefore,the aim of this paper is to distinguish automatically microstructural features between HSIL and cervical squamous cell carcinoma(CSCC)by means of polarization imaging techniques,and try to provide quantitative reference index for patho-logical diagnosis which can alleviate the workload of pathologists.Polarization images of the H&E stained histological slices were obtained by Mueller matrix microscope.The typical path-ological structure area was labeled by two experienced pathologists.Calculate the polarimetry basis parameter(PBP)statistics for this region.The PBP statistics(stat PBPs)are screened by mutual information(MI)method.The training method is based on a linear discriminant analysis(LDA)classier whichnds the most simplied linear combination from these stat PBPs and the accuracy remains constant to characterize the specic microstructural feature quantitatively in cervical squamous epithelium.We present results from 37 clinical patients with analysis regions of cervical squamous epithelium.The accuracy of PFP for recognizing HSIL and CSCC was 83.8%and 87.5%,respectively.This work demonstrates the ability of PFP to quantitatively charac-terize the cervical squamous epithelial lesions in the H&E pathological sections.Signicance:Polarization detection technology provides an effcient method for digital pathological diagnosis and points out a new way for automatic screening of pathological sections.

Practical Experience of Establishing German Standard Level 1 Perinatal Center in Chongqing Health Care for Women and Children

Germany,as a western developed country,has an advanced medical level,especially in the health care of very immature premature infants.We trace the medical history of perinatology to understand the development of perinatal centers in Germany.After analyzing the classification and function,hierarchical management and quality control systems of German perinatal centers,we established a German standard level 1 perinatal center in the Chongqing Health Center for Women and Children(CHCWC).During more than two years of practice,we changed concepts,continuously updated clinical knowledge and skills,developed a series o f high-quality work processes and supervision systems and introduced advanced medical equipment.We believe that the experience of establishing a German standard level 1 perinatal center and perinatal center network in Chongqing is worthy of being promoted to the Chinese maternal and child health care system.

QUANTITATIVE MUELLER MATRIX POLARIMETRY TECHNIQUES FOR BIOLOGICAL TISSUES

We propose and conduct both the rotating linear polarization imaging(RLPI)and Mueller matrix transformation(MMT)measurements of different biological tissue samples,and testify the capability of the Mueller matrix polarimetry for the anisotropic scattering media.The independent parameters extracted from the RLPI and MMT techniques are compared and analyzed.The tissue experimental results show that the parameters are closely related to the structural characteristics of the turbid scattering media,including the sizes of the scatterers,the angular distribution and order of alignment of thefibers.The results and conclusions in this paper may provide a potential method for the detection of precancerous and early stage cancerous tissues.Also,such studies represent the Mueller matrix transformation procedure which results in a set of parameters linking up the Mueller matrix elements to the structural and optical properties of the media.

A STUDY ON PENETRATION DEPTH OF POLARIZATION IMAGING

Optical clearing improves the penetration depth of optical measurements in turbid tissues.Polarization imaging has been demonstrated as a potentially promising tool for detecting cancers in superficial tissues,but its limited depth of detection is a major obstacle to the effective application in clinical diagnosis.In the present paper,detection depths of two polarization imaging methods,i.e.,rotating linear polarization imaging(RLPI)and degree of polarization imaging(DOPI),are examined quantitatively using both experiments and Monte Carlo simulations.The results show that the contrast curves of RLPI and DOPI are different.The characteristic depth of DOPI scales with transport mean free path length,and that of RLPI increases slightly with g.Both characteristic depths of RLPI and DOPI are on the order of transport mean free path length and the former is almost twice as large as the latter.It is expected that they should have different response to optical clearing process in tissues.

Application of Horizontal Well Seismic Geo-Steering Technology in XX Block Development

During the development phase horizontal wells are very efficient way to improve the production in the deep coal bed methane. The 8# coal seam in the XX block on the eastern edge of the Ordos Basin has challenges such as deep burial depth (>2000 m), thin coal sweet spot (3 m), and significant short-distance structural fluctuations. The challenges caused a high risk of missing targets and running out of the target layers, as well as difficulties in cementing and completion due to uneven well trajectories. To address these challenges, this paper focuses on solving the issues through detailed precise geological modeling, optimized trajectory design, and accurate seismic geology Steerable Drilling. 1) Based on reasonable velocity field construction and Time-Depth transformation, a precise directional model is constructed using the layer-by-layer approximation principle with reference to marker layers, improving the accuracy of the target spot and avoiding premature or delayed entry into the target;2) Based on a precise geological model, the dip angle of the strata ahead and the development of sweet spots are clearly defined, enabling optimized trajectory design for horizontal wells;3) Using “1 + N” dynamic modeling to update the geological model in real-time during the drilling process, and actively guide the drill bit through the horizontal segment smoothly by using multi-information judgment of the drill bit position. The actual drilling of 80 completed horizontal wells in this area show: That this approach effectively ensures the smooth trajectory and high-quality drilling rate of the horizontal well in the coal seam, providing a basis for subsequent hydraulic fracturing and increasing single-well production. At the same time, it has certain potential value and significance for similar coalbed methane developments under similar geological conditions.

Preoperative functional MRI localization of language areas in Chinese patients with brain tumors Validation with intraoperative electrocortical mapping

Ten Chinese patients with brain tumors involving language regions were selected. Preoperative functional MRI was performed to locate Broca＇s or Wernicke＇s area, and the cortex that was essential for language function was determined by electrocortical mapping. A site-by-site comparison between functional MRI and electrocortical mapping was performed with the aid of a neuronavigation device. Results showed that the sensitivity and specificity of preoperative functional MRI were 80.0% and 85.0% in Broca＇s area and 66.6% and 85.2% in Wemicke＇s area, respectively. These experimental findings indicate that functional MRI is an accurate, reliable technique with which to identify the location of Wernicke＇s area or Broca＇s area in patients with brain tumors.

Identification of serous ovarian tumors based on polarization imaging and correlation analysis with clinicopathological features

Ovarian cancer is one of the most aggressive and heterogeneous female tumors in the world,and serous ovarian cancer(SOC)is of particular concern for being the leading cause of ovarian cancer death.Due to its clinical and biological complexities,ovarian cancer is still considered one of the most di±cult tumors to diagnose and manage.In this study,three datasets were assembled,including 30 cases of serous cystadenoma(SCA),30 cases of serous borderline tumor(SBT),and 45 cases of serous adenocarcinoma(SAC).Mueller matrix microscopy is used to obtain the polarimetry basis parameters(PBPs)of each case,combined with a machine learning(ML)model to derive the polarimetry feature parameters(PFPs)for distinguishing serous ovarian tumor(SOT).The correlation between the mean values of PBPs and the clinicopathological features of serous ovarian cancer was analyzed.The accuracies of PFPs obtained from three types of SOT for identifying dichotomous groups(SCA versus SAC,SCA versus SBT,and SBT versus SAC)were 0.91,0.92,and 0.8,respectively.The accuracy of PFP for identifying triadic groups(SCA versus SBT versus SAC)was 0.75.Correlation analysis between PBPs and the clinicopathological features of SOC was performed.There were correlations between some PBPs(δ,β,q_(L),E_(2),rqcross,P_(2),P_(3),P_(4),and P_(5))and clinicopathological features,including the International Federation of Gynecology and Obstetrics(FIGO)stage,pathological grading,preoperative ascites,malignant ascites,and peritoneal implantation.The research showed that PFPs extracted from polarization images have potential applications in quantitatively differentiating the SOTs.These polarimetry basis parameters related to the clinicopathological features of SOC can be used as prognostic factors.