Comparison of a machine learning model with a conventional rule-based selective dry cow therapy algorithm for detection of intramammary infections.

We trained machine learning models to identify intramammary infections (IMI) in late lactation cows at dry-off to guide antibiotic treatment, and compared their performance to a rule-based algorithm that is currently used on dairy farms in the US. We conducted an observational test-characteristics study using a data set of 3,645 cows approaching dry-off from 68 US dairy herds. The outcome variables of interest were cow-level IMI caused by all pathogens, major pathogens, and Streptococcus and Strep-like organisms (SSLO), which were determined using aerobic culture of aseptic quarter-milk samples and identification of isolates using MALDI-TOF. Individual cow records were extracted from the farm software to create 53 feature variables at the cow and 39 at the herd-level which were derived from cow-level descriptive data, records of clinical mastitis events, results from routine testing of milk for volume and concentrations of somatic cell count (SCC), fat, and protein. ML algorithms evaluated were logistic regression, decision tree, random forest, light gradient-boosting machine, naïve bayes, and neural networks. For comparison, cows were also classified according to a conventional rule-based algorithm that considered a cow as high risk for IMI if she had at one or more high SCC (>200,000 cells/ml) tests or ≥2 cases of clinical mastitis during the lactation of enrollment. Area under the curve (AUC) and Youden's index were used to compare models, in addition to binary classification metrics, including sensitivity, specificity, and predictive values. ML models had slightly higher AUC and Youden's index values than the rule-based algorithm for all IMI outcomes of interest. However, these improvements in prediction accuracy were substantially less than what we had considered necessary for the technology to be a worthwhile alternative to the rule-based algorithm. Therefore, evidence is lacking to support the wholesale use of ML-guided selective dry cow therapy at the moment. We recommend that producers wanting to implement algorithm-guided SDCT use a rule-based method.

A fast all-optical 3D photoacoustic scanner for clinical vascular imaging.

The clinical assessment of microvascular pathologies (in diabetes and in inflammatory skin diseases, for example) requires the visualization of superficial vascular anatomy. Photoacoustic tomography (PAT) scanners based on an all-optical Fabry-Perot ultrasound sensor can provide highly detailed 3D microvascular images, but minutes-long acquisition times have precluded their clinical use. Here we show that scan times can be reduced to a few seconds and even hundreds of milliseconds by parallelizing the optical architecture of the sensor readout, by using excitation lasers with high pulse-repetition frequencies and by exploiting compressed sensing. A PAT scanner with such fast acquisition minimizes motion-related artefacts and allows for the volumetric visualization of individual arterioles, venules, venous valves and millimetre-scale arteries and veins to depths approaching 15 mm, as well as for dynamic 3D images of time-varying tissue perfusion and other haemodynamic events. In exploratory case studies, we used the scanner to visualize and quantify microvascular changes associated with peripheral vascular disease, skin inflammation and rheumatoid arthritis. Fast all-optical PAT may prove useful in cardiovascular medicine, oncology, dermatology and rheumatology.

[Effects of low dose skin tissue derived peptides on the function and collagen expression of keloid fibroblasts].

This study aims to investigate the effects of the skin tissue derived peptides on proliferation, apoptosis, migration and collagen expressions in keloid fibroblasts. From January 2015 to January 2017, patients with hypertrophic scar who underwent surgical excision in department of plastic surgery of Nanjing maternal and child health hospital were included in this retrospective study. Four peptides were selected from the differential peptides between human hypertrophic scar and normal skin tissue. They were named as peptide deregulated in hypertrophic scar 2-5 (PDHPS2-5). Bioinformatics and functional analysis were performed. A low dose of 10 µmol/L of four peptides were respectively added to the culture medium of human primary keloid fibroblasts for 24 h. Cell counting kit-8 (CCK-8) were used to detect the changes in cell viability. Cell apoptosis was detected by flow cytometry. Cell migration ability was checked by Transwell chamber. The protein expressions of collagen COL1A2 (Collagen type I alpha 2) and the myofibroblast marker gene ACTA2 (Actin alpha 2) were analyzed by Western blot. The results showed that bioinformatics prediction analysis revealed that peptide PDHPS4 has the longest half-life and the highest thermal stability. Compared with the control group, low dose of four peptides had no significant effect on the survival rate and apoptosis of keloid fibroblasts tested by CCK-8 assay and flowcytometry. Transwell analysis showed that one peptides (PDHPS5) can significantly inhibit the cell migration ability (The optical density value in Control is 0.81±0.11, in PDHPS5 is 0.27±0.03, t=8.61, P=0.001). Western blot analysis showed that four peptides (PDHPS2, PDHPS3, PDHPS4, PDHPS5) can significantly inhibit the protein expressions of COL1A2 (The relative protein band intensity in Control is 1.02±0.02, in PDHPS2 is 0.21±0.04, in PDHPS3 is 0.26±0.03, in PDHPS4 is 0.53±0.04, in PDHPS5 is 0.73±0.04, t=31.38, 38.54, 18.88, 11.07 respectively, all P value are less than 0.01). Three peptides (PDHPS2, PDHPS3, PDHPS5) can significantly inhibit the protein expressions of ACTA2 (The relative protein band intensity in Control is 1.02±0.02, in PDHPS2 is 0.64±0.05, in PDHPS3 is 0.77±0.06, in PDHPS5 is 0.47±0.07, t=12.08, 6.38, 14.06 respectively, all P value are less than 0.01). In conclusion, the differentially expressed peptides in human hypertrophic scar tissue can affect the function of keloid fibroblasts and collagen expressions to varying degrees. Among them, two peptides (PDHPS2,PDHPS3) significantly inhibit the protein expressions of COL1A2 and ACTA2. The peptide PDHPS5 has high stability, significantly suppresses cell migration, and reduces the protein expressions of COL1A2 and ACTA2, which may provide a new strategy for scar prevention and treatment.

Effects of Nicotinamide Mononucleotide Supplementation on Muscle and Liver Functions Among the Middle-Aged and Elderly: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Nicotinamide Mononucleotide (NMN) has gained attention as a precursor to Nicotinamide Adenine Dinucleotide (NAD+) in recent years, commonly utilized in anti-aging therapies. The anti-aging effects of NMN on muscle and liver functions in middleaged and elderly people are still unclear. OBJECTIVE: Based on available randomized controlled trials, we conducted a meta-analysis to evaluate the impact of NMN on muscle and liver functions in middle-aged and elderly individuals. METHODS: We conducted searches on three electronic databases (PubMed, Embase, Web of Science) for randomized controlled trials involving NMN interventions in middle-aged and elderly populations. Through the Cochrane Handbook, we assessed the specific methodological quality. All statistical analyses were obtained by Stata15, and statistical significance was set as P<0.05. RESULTS: There were 412 participants from 9 studies in this meta-analysis. Based on changes in gait speed (SMD: 0.34 m/s, 95%CI [0.03, 0.66] p = 0.033), NMN had significant effects on muscle mass. Moreover, NMN had a better effect on ALT (SMD: -0.29 IU/L, 95%CI [-0.55, -0.03] p = 0.028). Subgroup analysis indicated that administering a small dose of NMN exerted the most prominent impact on Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). CONCLUSION: NMN has positive efficacy in enhancing muscle function, reducing insulin resistance and lowering aminotransferase levels in middle-aged and elderly individuals. NMN is an encouraging and considerable drug for anti-aging treatment.

Fluorine accumulation characteristics of 85 tea tree (Camellia sinensis) varieties and its potential risk assessment.

Tea tree is a fluorine (F)-enriched plant, leading to much concern about the safety of drinking tea from tea tree (Camellia sinensis (L.) Kuntze). Tea tree is a perennial leaf-harvested crop, and tea production in China is generally categorized as spring tea, summer tea and autumn tea in its annual growth rounds. However, the seasonally dynamic changes of F content and accumulation in the leaves and its drinking safety are poorly understood. In this study, 85 tea varieties cultivated under the same conditions were investigated to analyze the seasonal variation of F content and it's relationships with F accumulation, aluminum (Al), calcium (Ca) and manganese (Mn) and hazard quotient (HQ) in young leaves (one bud and two leaves, YL) and mature leaves (canopy leaves, ML). The average F contents and accumulations were 350 mg kg-1 and 203 g ha-1 in YL, and they were 2451 mg kg-1 and 2578 g ha-1 in ML, respectively, with F mainly accumulated in ML. As the growing season progresses, the F content showed a gradual increase in YL, while a decrease in ML, inferring that F may be redistributed from mature leaves to young leaves. Additionally, the F content was quite different among tea varieties which are suitable for processing oolong tea, green tea, and black tea, with higher F accumulation in oolong tea varieties than in green and black tea varieties. Moreover, F content and accumulation could be obviously affected by the geographical origin of the tea tree varieties, with significantly higher F content in the varieties from F rich fluorite belts than other regions. Furthermore, F content and accumulation showed a significant positive correlation with the content of Al and Mn (p < 0.05). Based on a daily tea consumption of 8.7 g, the HQ was investigated to show that the proportion of tea leaves with HQ<1 made from spring, summer and autumn tender leaves of 85 varieties was 100 %, 90.6 % and 50.6 %, respectively, indicating that the tea with the best drinking safety comes from spring, followed by summer, and then autumn. This result suggests that it could be necessary to avoid planting tea trees in fluorite mining areas, choose low F tea tree varieties, and control the tenderness of fresh leaves in order to ensure the safety of tea drinking.

[Multiple locus variable number tandem repeat analysis genotype polymorphism of Bacillus anthracis in China].

Objective: To analyze the multiple locus variable number tandem repeat analysis (MLVA) genotype polymorphism of Bacillus (B.) anthracis and establish a MLVA genotype database of B. anthracis in China. Methods: B. anthracis strains isolated from different sources in China since 1947 were collected. Genotype identification was carried out using the MLVA15 genotyping protocol based on 15 variable number tandem repeat loci. The genotypes were uniformly numbered and named. The distribution characteristics of the MLVA genotypes of strains were analyzed. Software Bionumerics was used to construct clustering diagrams to analyze the genetic relationships. Results: The MLVA15 clustering analysis subdivided the isolates into 4 major groups and 91 genotypes, 54 of which were unique to China. The genotypes from MLVA15-CHN1 to MLVA15-CHN6 were widely distributed throughout China and in all eras, while other genotypes were restricted to certain regions or eras. Conclusions: This study established a MLVA genotype database of B. anthracis, which provides basis for the understanding of MLVA genetic polymorphisms and the control and molecular source tracing of the anthrax outbreaks in China.

[Association between maternal peri-conceptional exposures and risk of hypospadias and cryptorchidism in offspring].

Objective: To investigate the relationship between maternal exposures to peri-conceptional risk factors and the risk of hypospadias and cryptorchidism in offspring. Methods: Pregnant women who delivered male newborns and participated in the China birth cohort study between February 2018 and December 2020 at the research center of Beijing Obstetrics and Gynecology Hospital, Capital Medical University were selected for the study. All were enrolled at 6-13+6 weeks of their gestation. Baseline risk factor information was collected by questionnaire survey. Information on the outcome of hypospadias and cryptorchidism was obtained by clinical examination at birth and ultrasonography. Logistic regression was used to analyze the Odds Ratio (OR) and 95% Confidence Interval (95%CI) of each factor with respect to the onset of the outcome. Results: A total of 15, 833 pregnant women with an average age of (31.81±3.84) years were included. Among their offsprings, 113 were diagnosed as hypospadias or cryptorchidism (42 hypospadias, 69 cryptorchidism, and 2 both hypospadias and crypterchidism), with an incidence of 7.14‰. The results of multivariate logistic regression analysis showed that mothers with pregnancy history of birth defects (OR=3.01, 95%CI: 1.09-8.35), with preconception Hepatitis B infection (OR=4.74, 95%CI: 1.10-20.42), fetal growth restriction (OR=4.02, 95%CI: 2.10-7.68), multivitamin use since preconception (OR=1.98, 95%CI: 1.12-3.52), and never cook and eat at home (OR=2.17, 95%CI: 1.23-3.82) were risk factors for hypospadias and cryptorchidism (all P<0.05). Conclusions: Obesity in early pregnancy, preconception Hepatitis B infection, pregnancy history of birth defects, fetal growth restriction, multivitamin use before pregnancy, and rarely cook and eat at home were associated with an increased risk of hypospadias or cryptorchidism in their offsprings.

[Association between early pregnancy maternal blood pressure and risk of congenital heart disease in offspring].

Objective: To analyze the association between maternal blood pressure and congenital heart disease (CHD) in offspring. Methods: From February 2018 to December 2020, pregnant women who participated in the China birth cohort study in Beijing Obstetrics and Gynecology Hospital, Shenzhen Maternal and Child Healthcare Hospital and Chengdu Women's and Children's Central Hospital were enrolled in this study. The baseline and follow-up information were collected using an electronic data collection system. Stepwise logistic regression model was used to analyze the association between maternal blood pressure including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure difference (PP) in the first trimester of pregnancy and the risk of CHD in the offspring. A restrictive cubic spline curve was used to draw the dose-response curve between maternal blood pressure and CHD. Results: A total of 55 552 participants were included in this study. Of them, 31 038, 15 375 and 9 139 pregnant women were enrolled in Beijing Obstetrics and Gynecology Hospital, Shenzhen Maternal & Child Healthcare Hospital and Chendu Women's and Children's Central Hospital, respecitively. The age of pregnant women was (31.3±4.0) and the incidence of CHD in the offspring was 0.78% (435/55 552). Multivariable logistic regression model analysis showed that the increase of SBP (OR=1.01, 95%CI: 1.00-1.02), DBP (OR=1.01, 95%CI: 1.00-1.03) and MAP (OR=1.02, 95%CI: 1.00-1.03) in the first trimester were significantly associated with the risk of CHD in the offspring. The restrictive cubic spline analysis showed a positive linear association of SBP (Ptotal<0.001; Pnon-liear=0.315), DBP (Ptotal<0.001; Pnon-liear=0.928) and MAP (Ptotal<0.001; Pnon-liear=0.929) with the risk of CHD in the offspring. Conclusion: Maternal SBP, DBP and MAP in the first trimester of pregnancy were positively associated with the risk of CHD in the offspring.

Endoscopic ultrasound features of rectal melanoma: A case report and review of literature.

BACKGROUND: Rectal mucosal melanoma is a rare and highly aggressive disease. Common symptoms include anal pain, an anal mass, or bleeding. As such, the disease is usually detected on rectal examination of patients with other suspected anorectal diseases. However, due to its rarity and nonspecific symptoms, melanoma of the rectal mucosa is easily misdiagnosed. CASE SUMMARY: This report describes the case of a 58-year-old female patient who presented with a history of blood in her stool for the prior one or two months, without any identifiable cause. During colonoscopy, a bulge of approximately 2.2 cm × 2.0 cm was identified. Subsequently, the patient underwent endoscopic ultrasound (EUS) to characterize the depth of invasion of the lesions. EUS suggested a hypoechoic mucosal mass with involvement of the submucosal layer and heterogeneity of the internal echoes. Following surgical intervention, the excised tissue samples were examined and confirmed to be rectal malignant melanoma. The patient recovered well with no evidence of recurrence during follow-up. CONCLUSION: This case shows that colonoscopy with EUS and pathological examination can accurately diagnose rare cases of rectal mucosal melanoma.

Sinobdellalongitubulus, a new species of spiny eel (Pisces, Mastacembelidae) from the Zhu-Jiang Basin, with a note on the type locality of S.sinensis (Bleeker, 1870).

Background: The spiny eel genus Sinobdella belongs to the family Mastacembelidae of the order Synbranchiformes. Kottelat and Lim (1994) utilised Rhynchobdellasinensis as the type species to propose the genus. Currently, it contains a single species widespread in eastern and southern China and northern Vietnam. New information: Sinobdellalongitubulus, a new species of spiny eel, is here described from the Xi-Jiang of the Zhu-Jiang Basin in Guangxi Zhuang Autonomous Region, southern China. It differs from the single congeneric species S.sinensis in having a more or less white-brown reticulated pattern on the flank, two tubular anterior nostrils longer than or equal to the rostral appendage, an anal fin heavily mottled with dark brown markings and white spots and bearing a narrow white distal margin; shorter pre-anal length; and fewer abdominal vertebrae. The validity of this new species is corroborated by its monophyly recovered in a COI gene-based phylogenetic analysis and its significant sequence divergence with S.sinensis. A note on the type locality of S.sinensis is also given; its type specimen is possibly from mountain streams of Jiangxi Province, in the lower Chang-Jiang Basin.

Association between gestational cardiovascular health in the first trimester and pregnancy outcomes in the China birth cohort.

OBJECTIVES: To determine whether gestational cardiovascular health (CVH) during the first trimester is associated with a risk of adverse pregnancy outcomes. STUDY DESIGN: A multicentre prospective cohort; part of the China birth cohort study. METHODS: Pregnant women were recruited at 6-13+6 gestation weeks and followed to delivery to identify pregnancy outcomes. Gestational CVH in the first trimester was assessed using five CVH metrics: body mass index, smoking, blood pressure, glucose, and lipids. Multilevel modified Poisson regression models calculated the relative risks (RRs) and 95% confidence intervals (95% CIs) of gestational CVH for adverse pregnancy outcomes. RESULTS: Among 56,852 pregnant women, the mean score for gestational CVH during the first trimester was 9.1. Adjusting for confounding factors, each 1-point decrease in the total gestational CVH score significantly increased the risk of hypertensive disorders of pregnancy (RR = 1.682, 95% CI: 1.624-1.743), gestational diabetes mellitus (RR = 1.405, 95% CI: 1.384-1.426), preterm birth (RR = 1.184, 95% CI: 1.174-1.195), large for gestational age (RR = 1.224, 95% CI: 1.199-1.250), caesarean delivery (RR = 1.073, 95% CI: 1.049-1.097), and low Apgar score (RR = 1.131, 95% CI: 1.003-1.277) significantly increased. Meanwhile, the risk of small for gestational age decreased (SGA; RR = 0.922, 95% CI: 0.898-0.946). Worsened CVH categories significantly increased the risk of adverse pregnancy outcomes, excluding SGA. CONCLUSIONS: Poor gestational CVH in the first trimester significantly increases the risk of adverse pregnancy outcomes, emphasising the need for early improvement in gestational CVH.

MicroRNA 29 modulates ß-cell mitochondrial metabolism and insulin secretion via underlying miR-29-OXPHOS complex pathways.

AIM: MicroRNAs (miRNAs) regulate ß-cell function, and ß-cell mitochondria and insulin secretion are perturbed in diabetes. We aimed to identify key miRNAs regulating ß-cell mitochondrial metabolism and novel ß-cell miRNA-mitochondrial pathways. METHODS: TargetScan (http://www.targetscan.org/) was used to predict if 16 miRNAs implicated in ß-cell function target 27 cis-eGenes implicated in mitochondrial activity. The expression of candidate miRNAs and insulin secretion after 24 and 1 h pre-incubation in 2.8, 11.1- and 16.7-mM glucose was measured in clonal INS-1 832/13 ß-cells. MiR-29 silenced INS-1 832/13 cells were assessed for insulin secretion (glucose, pyruvate, and K+), target cis-eGene expression (Ndufv3 and Ndufa10 components of mitochondrial complex I (CI)), OXPHOS (CI-V) protein expression, and mitochondrial OXPHOS respiration/activity. The expression of differentially expressed miR-29 miRNAs was evaluated in Goto-Kakizaki (GK) rat, db/db mouse and type 2 diabetic (T2D) human islets, as well as NMRI mouse islets cultured under glucolipotoxic conditions. RESULTS: MiR-29, miR-15 and miR-124 were predicted to regulate ~20 cis-eGenes, while miR-29 alone was predicted to regulate ≥12 of these in rat and human species. MiR-29 expression and insulin secretion were reduced in INS-1 832/13 cells after 24 h in elevated glucose. MiR-29 knockdown increased all tested insulin secretory responses, Nudfv3, Ndufa10, complex I and II expression, and cellular mitochondrial OXPHOS. MiR-29 expression was reduced in db/db islets but increased in GK rat and T2D human islets. CONCLUSION: We conclude miR-29 is a key miRNA in regulating ß-cell mitochondrial metabolism and insulin secretion via underlying miR-29-OXPHOS complex pathways. Furthermore, we infer reduced miR-29 expression compensatorily enhances insulin secretion under glucotoxicity.

Effects of Polymannuronic Acid on the Intestinal Microbiota in Mice after Long-Term Intragastric Administration.

Polymannuronic acid (PM) is an alginate oligosaccharide derived from brown algae with a characterized structure and excellent biological activities. Herein, mice were given different doses of PM through 30-day-long-term intragastric administration, and the contents of the jejunum, ileum, and colon were analyzed by 16S rRNA gene sequencing technology for microbial diversity, and relevant experiments were verified according to the analysis results so as to comprehensively evaluate the effects of PM on the intestinal flora. The PM (400 mg/kg and 100 mg/kg) could regulate the microflora balance at the phylum level and increase the microflora richness in the jejunum, ileum, and colon of the mice. The PM could induce more strains that are negatively correlated with Escherichia, thereby reducing the relative abundance of Escherichia. Analysis of bacterial function showed that high and low doses of PM could promote lipid metabolism in the bacterial communities. Moreover, the PM could reduce serum total cholesterol and cholesterol ester levels in a concentration-dependent manner. High-dose PM could lead to colonic intestinal inflammation by increasing the relative abundance of multiple bacterial groups in the jejunum, ileum, and colon. Moreover, high-dose PM could increase lipopolysaccharide-binding protein and interleukin-1ß levels. Therefore, the dose of PM plays an important role in its efficacy, and its biological activity is dosedifferent.

Validation of remote anthropometric measurements in a rural randomized pediatric clinical trial in primary care settings.

Rural children are more at risk for childhood obesity but may have difficulty participating in pediatric weight management clinical trials if in-person visits are required. Remote assessment of height and weight observed via videoconferencing may provide a solution by improving the accuracy of self-reported data. This study aims to validate a low-cost, scalable video-assisted protocol for remote height and weight measurements in children and caregivers. Families were provided with low-cost digital scales and tape measures and a standardized protocol for remote measurements. Thirty-three caregiver and child (6-11 years old) dyads completed remote (at home) height and weight measurements while being observed by research staff via videoconferencing, as well as in-person measurements with research staff. We compared the overall and absolute mean differences in child and caregiver weight, height, body mass index (BMI), and child BMI adjusted Z-score (BMIaz) between remote and in-person measurements using paired samples t-tests and one sample t-tests, respectively. Bland-Altman plots were used to estimate the limits of agreement (LOA) and assess systematic bias. Simple regression models were used to examine associations between measurement discrepancies and sociodemographic factors and number of days between measurements. Overall mean differences in child and caregiver weight, height, BMI, and child BMIaz were not significantly different between remote and in-person measurements. LOAs were - 2.1 and 1.7 kg for child weight, - 5.2 and 4.0 cm for child height, - 1.5 and 1.7 kg/m2 for child BMI, - 0.4 and 0.5 SD for child BMIaz, - 3.0 and 2.8 kg for caregiver weight, - 2.9 and 3.9 cm for caregiver height, and - 2.1 and 1.6 kg/m2 for caregiver BMI. Absolute mean differences were significantly different between the two approaches for all measurements. Child and caregiver age were each significantly associated with differences between remote and in-person caregiver height measurements; there were no significant associations with other measurement discrepancies. Remotely observed weight and height measurements using non-research grade equipment may be a feasible and valid approach for pediatric clinical trials in rural communities. However, researchers should carefully evaluate their measurement precision requirements and intervention effect size to determine whether remote height and weight measurements suit their studies.Trial registration: ClinicalTrials.gov NCT04142034 (29/10/2019).

A review of conservation status of freshwater fish diversity in China.

China harbors a high species diversity of freshwater fishes not shared with any of its neighboring nations. Freshwater fish diversity in the country has been under severe threat from human activities over the past decades, thus conservation freshwater fishes and ecosystems is urgently needed. To accumulate baseline data for guiding protection actions, the third red list assessment of Chinese freshwater fishes was carried out. Among Chinese freshwater fishes assessed, there are 355 at-risk species (22.3% of the total), including 69 ranked as Critically Endangered, 97 as Endangered, and 189 as Vulnerable. Two species are classified as Extinct and one as Regionally Extinct. China's threat level seems to be lower than the known average level found in the IUCN's global assessment of freshwater fishes, but this is an artifact of a high rate of species classified as Data Deficient. Conservation of freshwater fishes is presently facing a grim situation in China. Imperilment of Chinese freshwater fishes is primarily attributed to habitat loss and degradation arising from human perturbations, particularly river damming. Despite the adoption of protected areas setting up, captive breeding and release, and a fishing moratorium, conservation efforts for freshwater fishes are compromised by disproportional attention in China's biodiversity conservation, baseline data deficiency, insufficiently designed protection networks, and inefficient or inadequate implementation of conservation strategies. To achieve the objectives of Chinese freshwater fish conservation, it is proposed to conduct a national-scale survey of fish diversity and reassess their at-risk status, develop systematic conservation planning of freshwater fish diversity and ecosystems, prioritize strategies for protected areas development, perform genetic-based captive breeding for releasing in concert with other protection actions, and implement flexible fishing moratorium strategies in different water bodies.

Descriptions of two new species of the botiid genus Leptobotia Bleeker, 1870 (Teleostei: Cypriniformes) from South China.

Two new species of Leptobotia are here described as L. rotundilobus from the Xin'an-Jiang of the upper Qiantang-Jiang basin in both Anhui and Zhejiang Provinces and the Cao'e-Jiang in Zhejiang Province, and L. paucipinna from the Qing-Jiang of the middle Chang-Jiang basin in Hubei Province, South China. Both have a plain brown body as found in L. bellacauda Bohlen & Slechtová, 2016, L. microphthalma Fu & Ye, 1983, L. posterodorsalis Chen & Lan, 1992 and L. tientainensis (Wu, 1930). The two new species are distinct from these species in vertebral counts, further from L. posterodorsalis in vent placement and further from the other three species in pectoral-fin length. Both differ in caudal-fin coloration and shape, and dorsal-fin location and coloration, and also in internal morphology. Their validity is confirmed by their own monophyly recovered in a phylogenetic analysis based on the mitochondrial cyt b and COI genes.

Age, growth, maturity and mortality of the tapetail anchovy Coilia brachygnathus (Engraulidae) in Lake Honghu, China.

The tapertail anchovy Coilia brachygnathus, a commercially important species mainly distributed along the mid-lower Chang-Jiang basin, is by far the most dominant species in Lake Honghu. To figure out its success in this semiclosed lake, some basic biological parameters of this anchovy were analysed based on samples seasonally collected from October 2020 to December 2021. The results demonstrated that the age classes of fished individuals varied from 0.5 to 3.5, with the majority (97.36%) being between 0.5 and 3 years old. The size at 50% maturity of 17.2 cm total length (TL) for females and 19.0 cm TL for males corresponded to 1 and 1.6 years, respectively. Coilia brachygnathus has a short life span, early sexual maturity and a relatively fast growth rate. The flourishing of the fish in the lake is mainly attributed to its short life span, early maturity, fast growth rate, closed fishing, pelagic spawners, the availability of plenty of food and low predation effect on it. Age 3.5 year occurs in an extremely small percentage of the total (<3%), indicating that a large number of larger-sized or older fish died after spawning, which is probably one of the major sources of water pollution if the closed fishing measure is adopted in Lake Honghu. Thus, individuals older than 2 years or more than 20.0 cm TL should be harvested. These findings have important management implications for the fish resources in Lake Honghu and beyond.

Dissecting embryonic and extraembryonic lineage crosstalk with stem cell co-culture.

Embryogenesis necessitates harmonious coordination between embryonic and extraembryonic tissues. Although stem cells of both embryonic and extraembryonic origins have been generated, they are grown in different culture conditions. In this study, utilizing a unified culture condition that activates the FGF, TGF-ß, and WNT pathways, we have successfully derived embryonic stem cells (FTW-ESCs), extraembryonic endoderm stem cells (FTW-XENs), and trophoblast stem cells (FTW-TSCs) from the three foundational tissues of mouse and cynomolgus monkey (Macaca fascicularis) blastocysts. This approach facilitates the co-culture of embryonic and extraembryonic stem cells, revealing a growth inhibition effect exerted by extraembryonic endoderm cells on pluripotent cells, partially through extracellular matrix signaling. Additionally, our cross-species analysis identified both shared and unique transcription factors and pathways regulating FTW-XENs. The embryonic and extraembryonic stem cell co-culture strategy offers promising avenues for developing more faithful embryo models and devising more developmentally pertinent differentiation protocols.

Resistomycin Inhibits Wnt/ß-Catenin Signaling to Induce the Apoptotic Death of Human Colorectal Cancer Cells.

Resistomycin is a natural antibiotic related to quinone that has been shown to exhibit robust antitumor activity. To further characterize the mechanistic basis for such activity, human colorectal cancer (CRC) cells were selected as a model to explore the role of Wnt/ß-catenin signaling in the ability of resistomycin to induce apoptotic cell death. These analyses revealed that resistomycin was able to suppress ß-catenin, TCF4, and GSK-3ß expression, together with that of the downstream targets c-Myc and survivin. This coincided with elevated cleaved caspase-3 and Bax protein levels and a decline in Bcl-2 content. When ß-catenin was silenced, this further enhanced the ability of resistomycin to induce apoptotic CRC cell death, whereas this apoptotic process was partially ablated when cells were treated using lithium chloride to activate Wnt/ß-catenin signaling. Overall, these results support a model wherein resistomycin inhibits Wnt/ß-catenin signaling within CRC cells, thereby inducing apoptotic death. Further research may be warranted to better clarify the potential utility of this compound as a candidate drug for use in the treatment of patients suffering from this form of cancer.

Targeted Degradation of XIAP is Sufficient and Specific to Induce Apoptosis in MYCN-overexpressing High-risk Neuroblastoma.

XIAP, the most potent mammalian inhibitor of apoptosis protein (IAP), critically restricts developmental culling of sympathetic neuronal progenitors, and is correspondingly overexpressed in most MYCN-amplified neuroblastoma tumors. Because apoptosis-related protein in the TGFß signaling pathway (ARTS) is the only XIAP antagonist that directly binds and degrades XIAP, we evaluated the preclinical effectiveness and tolerability of XIAP antagonism as a novel targeting strategy for neuroblastoma. We found that antagonism of XIAP, but not other IAPs, triggered apoptotic death in neuroblastoma cells. XIAP silencing induced apoptosis while overexpression conferred protection from drug-induced apoptosis. From a screen of IAP inhibitors, first-in-class ARTS mimetic A4 was most effective against high-risk and high XIAP-expressing neuroblastoma cells, and least toxic toward normal liver- and bone marrow-derived cells, compared with pan-IAP antagonists. On target engagement assays and nuclear magnetic resonance spectroscopy, A4 was observed to degrade rather than inhibit XIAP, catalyzing rapid degradation of XIAP through the ubiquitin-proteasome pathway. In MYCN-amplified neuroblastoma patient-derived xenografts, A4 significantly prolonged survival as a single agent, and demonstrated synergism with standard-of-care agents to reduce their effective required doses 3- to 6-fold. Engagement and degradation of XIAP by ARTS mimetics is a novel targeting strategy for neuroblastoma that may be especially effective against MYCN-amplified disease with intrinsically high XIAP expression. First-in-class ARTS mimetic A4 demonstrates preclinical efficacy and warrants further development and study. SIGNIFICANCE: XIAP degradation is sufficient to kill MYCN-amplified neuroblastoma which overexpresses and relies on XIAP as a brake against cell death, without affecting normal cells.