Hiptage yangshuoensis (Malpighiaceae), a new species on karst hills close to Lijiang River, Guangxi, China, based on molecular and morphological data.

Hiptage yangshuoensis K.Tan & K.S.Nguyen, a new species of Hiptage collected from a karst cliff close to the Lijiang River, Northeast of Guangxi Zhuang Autonomous Region, China, is described and illustrated based on molecular and morphological data. Hiptage yangshuoensis shares some morphological similarities with the H. multiflora F.N.Wei, but easily distinguished by its long pedicels with articulate at top, one large calyx gland, oblanceolate middle wing and lanceolate lateral wings of samara, and young branch covered rusty sericeous. The new species status is also supported by molecular phylogenetic analyses based on nuclear ribosome internal transcribed spacer (nrITS), which showed distinct systematic distinctiveness from the most morphologically similar species, H. multiflora.

Design, synthesis, and biological evaluation of RSL3-based GPX4 degraders with hydrophobic tags.

Ferroptosis is a new type of programmed cell death characterized by iron-dependent lipid peroxidation, during which glutathione peroxidase 4 (GPX4) plays an essential role and is well-recognized as a promising therapeutic target for cancer treatment. Although some GPX4 degradation molecules have been developed to induce ferroptosis, the discovery of GPX4 degraders with hydrophobic tagging (HyT) as an innovative approach is more challenging. Herein, we designed and synthesized a series of HyT degraders by linking the GPX4 inhibitor RSL3 with a hydrophobic and bulky group of adamantane. Among them, compound R8 is a potent degrader (DC50, 24h = 0.019 µM) which can effectively degrade GPX4 in a dose- and time-dependent manner. Furthermore, compound R8 exhibited superior in vitro antitumor potency against HT1080 and MDA-MB-231 cell lines with IC50 values of 24 nM and 32 nM respectively, which are 4 times more potent than parental compound RSL3. Mechanistic investigation evidenced that R8 consumes GPX4 protein mainly through the ubiquitin proteasome (UPS) and enables to induce the accumulation of LPO, thereby triggering ferroptosis. Our work presented the novel GPX4 degrader of R8 by HyT strategy, and provided a promising pathway of degradation agents for the treatment of ferroptosis relevant diseases.

Oxytocin Alleviates Colitis and Colitis-Associated Colorectal Tumorigenesis via Noncanonical Fucosylation.

Colon cancer is increasing worldwide and is commonly regarded as hormone independent, yet recent reports have implicated sex hormones in its development. Nevertheless, the role of hormones from the hypothalamus-hypophysis axis in colitis-associated colorectal cancer (CAC) remains uncertain. In this study, we observed a significant reduction in the expression of the oxytocin receptor (OXTR) in colon samples from both patient with colitis and patient with CAC. To investigate further, we generated mice with an intestinal-epithelium-cell-specific knockout of OXTR. These mice exhibited markedly increased susceptibility to dextran-sulfate-sodium-induced colitis and dextran sulfate sodium/azoxymethane-induced CAC compared to wild-type mice. Our findings indicate that OXTR depletion impaired the inner mucus of the colon epithelium. Mechanistically, oxytocin was found to regulate Mucin 2 maturation through ß1-3-N-acetylglucosaminyltransferase 7 (B3GNT7)-mediated fucosylation. Interestingly, we observed a positive correlation between B3GNT7 expression and OXTR expression in human colitis and CAC colon samples. Moreover, the simultaneous activations of OXTR and fucosylation by l-fucose significantly alleviated tumor burden. Hence, our study unveils oxytocin's promising potential as an affordable and effective therapeutic intervention for individuals affected by colitis and CAC.

Development and validation of a nomogram to predict medication risk based on a knowledge, attitude and practice (KAP) survey of residents in Shanxi Province, China.

Objective: Unsafe medication practices and medication errors are a major cause of harm in healthcare systems around the world. This study aimed to explore the factors that influence the risk of medication and provide medication risk evaluation model for adults in Shanxi province, China. Methods: The data was obtained from the provincial questionnaire from May to December 2022, relying on the random distribution of questionnaires and online questionnaires by four hospitals in Shanxi Province. Multiple linear regression analysis was used to explore the factors affecting the KAP score of residents. Univariate and multivariate logistic regression was used to determine the independent risk factors, and the nomogram was verified by receiver operating characteristic curve, calibration and decision curve analysis. Results: A total of 3,388 questionnaires were collected, including 3,272 valid questionnaires. The average scores of drugs KAP were 63.2 ± 23.04, 33.05 ± 9.60, 23.67 ± 6.75 and 33.16 ± 10.87, respectively. On the evaluation criteria of the questionnaire, knowledge was scored "fair", attitude and practice were scored "good". Sex, monthly income, place of residence, insurance status, education level, and employment were regarded as independent risk factors for medication and a nomogram was established by them. Conclusion: Males, low-income, and low-educated people are important factors affecting the risk of medication. The application of the model can help residents understand the risk of their own medication behavior and reduce the harm of medication.

The genetic status and rescue measure for a geographically isolated population of Amur tigers.

The Amur tiger is currently confronted with challenges of anthropogenic development, leading to its population becoming fragmented into two geographically isolated groups: smaller and larger ones. Small and isolated populations frequently face a greater extinction risk, yet the small tiger population's genetic status and survival potential have not been assessed. Here, a total of 210 samples of suspected Amur tiger feces were collected from this small population, and the genetic background and population survival potentials were assessed by using 14 microsatellite loci. Our results demonstrated that the mean number of alleles in all loci was 3.7 and expected heterozygosity was 0.6, indicating a comparatively lower level of population genetic diversity compared to previously reported studies on other subspecies. The genetic estimates of effective population size (Ne) and the Ne/N ratio were merely 7.6 and 0.152, respectively, representing lower values in comparison to the Amur tiger population in Sikhote-Alin (the larger group). However, multiple methods have indicated the possibility of genetic divergence within our isolated population under study. Meanwhile, the maximum kinship recorded was 0.441, and the mean inbreeding coefficient stood at 0.0868, both of which are higher than those observed in other endangered species, such as the African lion and the grey wolf. Additionally, we have identified a significant risk of future extinction if the lethal equivalents were to reach 6.26, which is higher than that of other large carnivores. Further, our simulation results indicated that an increase in the number of breeding females would enhance the prospects of this population. In summary, our findings provide a critical theoretical basis for further bailout strategies concerning Amur tigers.

Methodology Advances in Vertebrate Age Estimation.

Age is a core metric in vertebrate management, and the correct estimation of the age of an individual plays a principal role in comprehending animal behavior, identifying genealogical information, and assessing the potential reproductive capacity of populations. Vertebrates have a vertebral column and a distinct head containing a developed brain; they have played an important role in the study of biological evolution. However, biological age estimations constantly exhibit large deviations due to the diversity of vertebrate taxon species, sample types, and determination methods. To systematically and comprehensively understand age estimation methods in different situations, we classify the degree of damage to vertebrates during sample collection, present the sample types and their applications, list commonly applied methods, present methodological recommendations based on the combination of accuracy and implementability, and, finally, predict future methods for vertebrate age assessments, taking into account the current level of research and requirements. Through comprehensive data gathering and compilation, this work serves as an introduction and summary for those who are eager to catch up on related fields and facilitates the rapid and accurate selection of an evaluation method for researchers engaged in related research. This is essential to promote animal conservation and guide the smooth implementation of conservation management plans.

Flexible Bioinspired Healable Antibacterial Electronics for Intelligent Human-Machine Interaction Sensing.

Flexible electronic sensors are receiving numerous research interests for their potential in electronic skins (e-skins), wearable human-machine interfacing, and smart diagnostic healthcare sensing. However, the preparation of multifunctional flexible electronics with high sensitivity, broad sensing range, fast response, efficient healability, and reliable antibacterial capability is still a substantial challenge. Herein, bioinspired by the highly sensitive human skin microstructure (protective epidermis/spinous sensing structure/nerve conduction network), a skin bionic multifunctional electronics is prepared by face-to-face assembly of a newly prepared healable, recyclable, and antibacterial polyurethane elastomer matrix with conductive MXene nanosheets-coated microdome array after ingenious templating method as protective epidermis layer/sensing layer, and an interdigitated electrode as signal transmission layer. The polyurethane elastomer matrix functionalized with triple dynamic bonds (reversible hydrogen bonds, oxime carbamate bonds, and copper (II) ion coordination bonds) is newly prepared, demonstrating excellent healability with highly healing efficiency, robust recyclability, and reliable antibacterial capability, as well as good biocompatibility. Benefiting from the superior mechanical performance of the polyurethane elastomer matrix and the unique skin bionic microstructure of the sensor, the as-assembled flexible electronics exhibit admirable sensing performances featuring ultrahigh sensitivity (up to 1573.05 kPa-1 ), broad sensing range (up to 325 kPa), good reproducibility, the fast response time (≈4 ms), and low detection limit (≈0.98 Pa) in diagnostic human healthcare monitoring, excellent healability, and reliable antibacterial performance.

Exploratory analysis of the associations between neonicotinoids insecticides and serum lipid profiles among US adults: A cross-sectional, population-based study.

Neonicotinoid insecticides (NNIs) are widely used in agriculture, horticulture, forestry, and household environment, but their potential impact on human health remains a subject of concern. This study aimed to investigate the relationship between NNIs and their metabolites in urine with serum lipid profiles in adults using data from the National Health and Nutrition Examination Survey (NHANES) 2015-2016. The study included 1192 participants aged over 20 years with urinary NNIs levels, serum lipid parameter levels and potential confounders. Urinary concentrations of NNIs, including imidacloprid, acetamiprid, clothianidin, thiacloprid, N-desmethyl-acetamiprid, and 5-hydroxy-imidacloprid, were quantified. Serum lipids profiles, such as total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (Apo-B), were assessed. Considering the effects of lipid-lowering medications, the censored normal regression model was used to explore the associations between urinary NNIs and TC, TG, HDL-C, LDL-C and Apo-B levels. The results revealed a significant increase of 9.0 mg/dL (95%CI: 2.0, 16.1) in TC levels among participants with detectable N-desmethyl-acetamiprid compared to those with undetectable levels. Stratified analysis indicated that the association between N-desmethyl-acetamiprid and HDL-C levels was more pronounced among participants aged ≥ 46 years compared to those aged between 20 and 45 years with undetectable N-desmethyl-acetamiprid (pinteraction=0.044). Additionally, there were marginal effect modification of BMI on the association between N-desmethyl-acetamiprid and LDL-C (pinteraction=0.097) and Apo-B (pinteraction=0.052) levels. Specifically, participants with BMI ≥ 25 kg/m² and detectable N-desmethyl-acetamiprid tended to have higher LDL-C and Apo-B levels compared to those with BMI < 25 kg/m² and undetectable N-desmethyl-acetamiprid. However, no significant associations were observed between other NNIs and lipid profiles in the present study. To validate these findings, further longitudinal studies with larger sample sizes should be conducted, particularly within populations characterized by a high detection rate of NNIs.

Safety and outcome of early enteral nutrition in patients receiving extracorporeal membrane oxygenation.

OBJECTIVE: To explore the benefits and risks of early enteral nutrition (EN) in patients receiving extracorporeal membrane oxygenation (ECMO). METHODS: A single center retrospective review was performed including patients receiving ECMO for more than 24 h from May 2014 to July 2021. RESULTS: A total of sixty-five patients were enrolled, of which thirty-six patients (55.4%) received early EN. On ECMO day 3rd, 7th and 14th, the median energy intake through EN in the early EN group was 500 kcal (IQR:300, 880), 1000 kcal (IQR: 500, 1500) and 1000 kcal (500, 1500), representing 29.7%, 66.7% and 66.7% of energy target, respectively. Thirteen (36.1%) patients had EN intolerance in the early EN group, which is significantly lower than that in the delayed EN group (82.8%, P < 0.001). The most common reasons for EN intolerance were abdominal distention (22.2%), followed by elevated gastric residual volume (8.3%) in the early EN group. Forty-three (66.1%) patients successfully weaned off ECMO, with higher rate in the early EN group than in the delayed EN group (80.6% vs 48.3%, p = 0.006). Nineteen patients (52.8%) survived in the early EN group, which is also significantly higher than that in the delayed EN group (20.7%, P = 0.008). Patients receiving early enteral nutrition significantly reduced the mortality rate and the adjusted mortality hazard ratio was 0.22 (95%CI:0.10, 0.47). CONCLUSION: Early EN was safe and well-tolerated and can reduce the in-hospital mortality of patients receiving ECMO. For patients receiving ECMO, EN started with hypocaloric doses within 48 h of ECMO initiation is recommend.

A hyperthermic seizure unleashes a surge of spreading depolarizations in Scn1a-deficient mice.

Spreading depolarization (SD) is a massive wave of cellular depolarization that slowly migrates across the brain gray matter. Cortical SD is frequently generated following brain injury, while less is understood about its potential contribution to genetic disorders of hyperexcitability, such as SCN1A-deficient epilepsy, in which febrile seizure often contributes to disease initiation. Here we report that spontaneous SD waves are predominant EEG abnormalities in the Scn1a-deficient mouse (Scn1a+/R1407X) and undergo sustained intensification following a single hyperthermic seizure. Chronic DC-band EEG recording detected spontaneous SDs, seizures, and seizure-SD complexes in Scn1a+/R1407X mice but not WT littermates. The SD events were infrequent, while a single hyperthermia-induced seizure robustly increased SD frequency over 4-fold during the initial postictal week. This prolonged neurological aftermath could be suppressed by memantine administration. Video, electromyogram, and EEG spectral analysis revealed distinct neurobehavioral patterns; individual seizures were associated with increased motor activities, while SDs were generally associated with immobility. We also identified a stereotypic SD prodrome, detectable over a minute before the onset of the DC potential shift, characterized by increased motor activity and bilateral EEG frequency changes. Our study suggests that cortical SD is a pathological manifestation in SCN1A-deficient epileptic encephalopathy.

Application of LEARNS model based on Triangle stratified model on the management of out-patients with type 2 diabetes mellitus / 中国实用护理杂志

Objective:To analyze the effects of stratified follow-up intervention combined with LEARNS model on self-management, glucose metabolism, compliance and satisfaction in patients with type 2 diabetes mellitus (T2DM).Methods:This study was a quasi-experimental study. A total of 212 patients with T2DM who visited the DM nursing clinic of Beijing Tiantan Hospital, Capital Medical University from June 2020 to May 2021 were selected and divided into control group (102 cases) and intervention group (110 cases) according to the treatment time. All the patients received the conventional medical treatment and health education guidance for 6 months, at the same time, the intervention group received management of the triangle stratified model combined with LEARNS mode. The glucose metabolism, self-management behavior, satisfaction and compliance were compared before and after the intervention.Results:Before the intervention, the baseline data of the 2 groups had no significant difference(all P>0.05) and were comparable. Three and six months after the intervention, the HbA1c values of the intervention group were (6.18 ± 0.57)% and (6.40 ± 0.47)%, which were significant better than those in the control group, (6.74 ± 0.90)% and (6.99 ± 0.91)%, the differences were significant ( t=8.05 and 9.12, both P<0.01). Three and six months after the intervention, the SDASC values in the intervention group were (46.51 ± 5.80) and (44.41 ± 5.61), which were higher than those in the control group, (43.45 ± 4.20) and (42.08 ± 3.67), the difference were significant ( t=6.56 and 5.32, both P<0.01). Three and six months after the intervention, the compliance and patient satisfaction of intervention group were better than those in the control group ( χ2=5.52 and 7.26, t=7.02 and 15.75, all P<0.05). Conclusions:Triangle hierarchical management combined with LEARNS model can effectively improve the blood glucose levels of T2DM patients as well as their self-management levels, satisfaction and compliance, which can help nurses reasonably allocate follow-up time.

Human 8-cell embryos enable efficient induction of disease-preventive mutations without off-target effect by cytosine base editor

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.

Emx1-Cre Is Expressed in Peripheral Autonomic Ganglia That Regulate Central Cardiorespiratory Functions.

The Emx1-IRES-Cre transgenic mouse is commonly used to direct genetic recombination in forebrain excitatory neurons. However, the original study reported that Emx1-Cre is also expressed embryonically in peripheral autonomic ganglia, which could potentially affect the interpretation of targeted circuitry contributing to systemic phenotypes. Here, we report that Emx1-Cre is expressed in the afferent vagus nerve system involved in autonomic cardiorespiratory regulatory pathways. Our imaging studies revealed expression of Emx1-Cre driven tdtomato fluorescence in the afferent vagus nerve innervating the dorsal medulla of brainstem, cell bodies in the nodose ganglion, and their potential target structures at the carotid bifurcation such as the carotid sinus and the superior cervical ganglion (SCG). Photostimulation of the afferent terminals in the nucleus tractus solitarius (NTS) in vitro using Emx1-Cre driven ChR2 reliably evoked EPSCs in the postsynaptic neurons with electrophysiological characteristics consistent with the vagus afferent nerves. In addition, optogenetic stimulation targeting the Emx1-Cre expressing structures identified in this study, such as vagus nerve, carotid bifurcation, and the dorsal medulla surface transiently depressed cardiorespiratory rate in urethane anesthetized mice in vivo Together, our study demonstrates that Emx1-IRES-Cre is expressed in the key peripheral autonomic nerve system and can modulate cardiorespiratory function independently of forebrain expression. These results raise caution when interpreting systemic phenotypes of Emx1-IRES-Cre conditional recombinant mice, and also suggest the utility of this line to investigate modulators of the afferent vagal system.

Wavelet methods reveal big cat activity patterns and synchrony of activity with preys.

Appropriate temporal and spatial scales are important prerequisites for obtaining reliable results in studies of wildlife activity patterns and interspecific interactions. The spread of camera-trap technology has increased interest in and feasibility of studying the activity patterns and interspecific interactions of wildlife. However, such studies are often conducted at arbitrary spatial and temporal scales, and the methods used impose scale on the study rather than determining how activity and species interactions change with spatial scale. In this study, we used a wavelet-based approach to determine the temporal and spatial scales for activity patterns and interspecific interactions on Amur leopard and their ungulate prey species that were recorded using camera traps in the main Amur leopard occurrence region in northeast China. Wavelets identified that Amur leopards were more active in spring and fall than summer, and fluctuated with periodicities of 9 and 17 days, respectively. Synchronous relationships between leopards and their prey commonly occurred in spring and fall, with a periodicity of about 20 days, indicating the appropriate seasons and temporal scales for interspecific interaction research. The influence of human activities on the activity patterns of Amur leopard or prey species often occurred over longer time periods (60-64 days). Two-dimensional wavelet analyses showed that interactions between leopard and prey were more significant at spatial scales of 1 km2 . Overall, our study provides a feasible approach to studying the temporal and spatial scales for wildlife activity patterns and interspecific interaction research using camera trap data.

The Immune and Inflammatory Basis of Acquired Pediatric Cardiac Disease.

Children with acquired heart disease face significant health challenges, including a lifetime of strict medical management, multiple cardiac surgeries, and a high mortality risk. Though the presentation of these conditions is diverse, a unifying factor is the role of immune and inflammatory responses in their development and/or progression. For example, infectious agents have been linked to pediatric cardiovascular disease, leading to a large health burden that disproportionately affects low-income areas. Other implicated mechanisms include antibody targeting of cardiac proteins, infection of cardiac cells, and inflammation-mediated damage to cardiac structures. These changes can alter blood flow patterns, change extracellular matrix composition, and induce cardiac remodeling. Therefore, understanding the relationship between the immune system and cardiovascular disease can inform targeted diagnostic and treatment approaches. In this review, we discuss the current understanding of pediatric immune-associated cardiac diseases, challenges in the field, and areas of research with potential for clinical benefit.

Congenital Heart Disease: An Immunological Perspective.

Congenital heart disease (CHD) poses a significant global health and economic burden-despite advances in treating CHD reducing the mortality risk, globally CHD accounts for approximately 300,000 deaths yearly. Children with CHD experience both acute and chronic cardiac complications, and though treatment options have improved, some remain extremely invasive. A challenge in addressing these morbidity and mortality risks is that little is known regarding the cause of many CHDs and current evidence suggests a multifactorial etiology. Some studies implicate an immune contribution to CHD development; however, the role of the immune system is not well-understood. Defining the role of the immune and inflammatory responses in CHD therefore holds promise in elucidating mechanisms underlying these disorders and improving upon current diagnostic and treatment options. In this review, we address the current knowledge coinciding CHDs with immune and inflammatory associations, emphasizing conditions where this understanding would provide clinical benefit, and challenges in studying these mechanisms.

Application of Laparoscopy in Comprehensive Staging Operation of Ovarian Cancer Based on Electronic Medical Blockchain Technology.

Ovarian cancer has always entangled most women. Studies have shown that the prevalence of ovarian cancer ranks third in female reproductive malignancies, and the mortality rate has always been the highest. The reason is mainly because the diagnosis and treatment of preovarian cancer has always been a big problem. However, the emergence of laparoscopy can well solve this problem, especially laparoscopy assisted by blockchain technology, which plays a huge role in the overall staging of ovarian cancer. This article proposes the application research of laparoscopy in the comprehensive staging of ovarian cancer based on electronic medical blockchain technology. First of all, this article uses the literature method to study the clinical characteristics and surgical classification of ovarian cancer, as well as the application status of blockchain technology and laparoscopic technology. Secondly, it designed an application experiment based on electronic medical blockchain technology to assist laparoscopy in the comprehensive staging of ovarian cancer and analyzed the comparison of the laparoscopic group and the control group in the comprehensive staging of ovarian cancer. The results of the study showed that the amount of bleeding in the laparoscopic group was 103.5 ml, while the amount of bleeding in the control group was 141.1 ml; the proportion of tertiary pain in the laparoscopic group was 11.37%, and the proportion of tertiary pain in the control group was 31.82%. From this, it can be seen that, in the comprehensive staging operation for ovarian cancer, the laparoscopic group has less intraoperative blood loss than the control group and lower pain, and the treatment effect is better.

Application of ITO Method in Determination of Special Half-Sibling Relationship / 法医学杂志

OBJECTIVES@#To identify whether the relationship between Zhang A, Zhang B, Zhang C and Zhang X is the half-sibling relationship whose mother is sister (hereinafter referred to as the special half-sibling relationship) or the common first cousin relationship and discuss the application of ITO method in discriminating the special kinship.@*METHODS@#DNA was extracted from blood stain of four identified individuals, PowerPlex® 21 System and AGCU 21+1 STR kit were used to detect autosomal STR genetic markers. Investigator® Argus X-12 QS kit was used to detect the X chromosome STR genetic markers, the special half-sibling index (SHSI) and first cousin index (FCI) and their likelihood ratio (LR) were calculated by ITO method.@*RESULTS@#The LR results of SHSI to FCI, which were calculated based on autosomal STR genotyping and the analysis of X-STR genotyping results suggested that the relationship between Zhang A, Zhang B, Zhang C and Zhang X was inclined to be a special half-sibling relationship.@*CONCLUSIONS@#For the identification of special kinship, it is necessary to comprehensively apply various genetic markers according to the case. After the conclusion that shared alleles cannot be excluded from the analysis, ITO method can be further used to establish discriminant assumptions according to the specific case to obtain objective and reliable identification opinions.