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Heart rate variability (HRV) is an important metric in cardiovascular health monitoring. Spectral analysis of HRV provides essential insights into the functioning of the cardiac autonomic nervous system. However, data artefacts could degrade signal quality, potentially leading to unreliable assessments of cardiac activities. In this study, we introduced a novel approach for estimating uncertainties in HRV spectrum based on matrix completion. The proposed method utilises the low-rank characteristic of HRV spectrum matrix to efficiently estimate data uncertainties. In addition, we developed a refined matrix completion technique to enhance the estimation accuracy and computational cost. Benchmarking on five public datasets, our model shows effectiveness and reliability in estimating uncertainties in HRV spectrum, and has superior performance against five deep learning models. The results underscore the potential of our developed matrix completion-based statistical machine learning model in providing reliable HRV spectrum uncertainty estimation.

Abstract By September 2022, more than 600 million cases of SARS-CoV-2 infection have been reported globally, resulting in over 6.5 million deaths. COVID-19 mortality risk estimators are often, however, developed with small unrepresentative samples and with methodological limitations. It is highly important to develop predictive tools for pulmonary embolism (PE) in COVID-19 patients as one of the most severe preventable complications of COVID-19. Early recognition can help provide life-saving targeted anti-coagulation therapy right at admission. Using a dataset of more than 800,000 COVID-19 patients from an international cohort, we propose a cost-sensitive gradient-boosted machine learning model that predicts occurrence of PE and death at admission. Logistic regression, Cox proportional hazards models, and Shapley values were used to identify key predictors for PE and death. Our prediction model had a test AUROC of 75.9% and 74.2%, and sensitivities of 67.5% and 72.7% for PE and all-cause mortality respectively on a highly diverse and held-out test set. The PE prediction model was also evaluated on patients in UK and Spain separately with test results of 74.5% AUROC, 63.5% sensitivity and 78.9% AUROC, 95.7% sensitivity. Age, sex, region of admission, comorbidities (chronic cardiac and pulmonary disease, dementia, diabetes, hypertension, cancer, obesity, smoking), and symptoms (any, confusion, chest pain, fatigue, headache, fever, muscle or joint pain, shortness of breath) were the most important clinical predictors at admission. Age, overall presence of symptoms, shortness of breath, and hypertension were found to be key predictors for PE using our extreme gradient boosted model. This analysis based on the, until now, largest global dataset for this set of problems can inform hospital prioritisation policy and guide long term clinical research and decision-making for COVID-19 patients globally. Our machine learning model developed from an international cohort can serve to better regulate hospital risk prioritisation of at-risk patients.

Abstract Collaborative efforts in artificial intelligence (AI) are increasingly common between high-income countries (HICs) and low- to middle-income countries (LMICs). Given the resource limitations often encountered by LMICs, collaboration becomes crucial for pooling resources, expertise, and knowledge. Despite the apparent advantages, ensuring the fairness and equity of these collaborative models is essential, especially considering the distinct differences between LMIC and HIC hospitals. In this study, we show that collaborative AI approaches can lead to divergent performance outcomes across HIC and LMIC settings, particularly in the presence of data imbalances. Through a real-world COVID-19 screening case study, we demonstrate that implementing algorithmic-level bias mitigation methods significantly improves outcome fairness between HIC and LMIC sites while maintaining high diagnostic sensitivity. We compare our results against previous benchmarks, utilizing datasets from four independent United Kingdom Hospitals and one Vietnamese hospital, representing HIC and LMIC settings, respectively.

Abstract Deep neural networks have been integrated into the whole clinical decision procedure which can improve the efficiency of diagnosis and alleviate the heavy workload of physicians. Since most neural networks are supervised, their performance heavily depends on the volume and quality of available labels. However, few such labels exist for rare diseases (e.g., new pandemics). Here we report a medical multimodal large language model (Med-MLLM) for radiograph representation learning, which can learn broad medical knowledge (e.g., image understanding, text semantics, and clinical phenotypes) from unlabelled data. As a result, when encountering a rare disease, our Med-MLLM can be rapidly deployed and easily adapted to them with limited labels. Furthermore, our model supports medical data across visual modality (e.g., chest X-ray and CT) and textual modality (e.g., medical report and free-text clinical note); therefore, it can be used for clinical tasks that involve both visual and textual data. We demonstrate the effectiveness of our Med-MLLM by showing how it would perform using the COVID-19 pandemic “in replay”. In the retrospective setting, we test the model on the early COVID-19 datasets; and in the prospective setting, we test the model on the new variant COVID-19-Omicron. The experiments are conducted on 1) three kinds of input data; 2) three kinds of downstream tasks, including disease reporting, diagnosis, and prognosis; 3) five COVID-19 datasets; and 4) three different languages, including English, Chinese, and Spanish. All experiments show that our model can make accurate and robust COVID-19 decision-support with little labelled data.

Abstract Background Associations between kidney function and dementia risk are inconclusive. Chronic kidney disease (CKD) severity is determined by levels of both estimated glomerular filtration rate (eGFR) and the urine albumin to creatinine ratio (ACR). However, whether there is a graded increase in dementia risk for worse eGFR in each ACR category is unclear. Also, whether genetic risk for dementia impacts the associations is unknown. The current study aims to investigate the associations between eGFR and albuminuria with dementia risk both individually and jointly, whether the associations vary by different follow-up periods, and whether genetic factors modified the associations. Methods In 202,702 participants aged ≥ 60 years from the UK Biobank, Cox proportional-hazards models were used to examine the associations between eGFR and urine albumin creatinine ratio (ACR) with risk of incident dementia. GFR was estimated based on serum creatinine, cystatin C, or both. The models were restricted to different follow-up periods (

Abstract We aimed to identify potential novel predictors for breast cancer among post-menopausal women, with pre-specified interest in the role of polygenic risk scores (PRS) for risk prediction. We utilised an analysis pipeline where machine learning was used for feature selection, prior to risk prediction by classical statistical models. An “extreme gradient boosting” (XGBoost) machine with Shapley feature-importance measures were used for feature selection among $$\approx$$ ≈ 1.7 k features in 104,313 post-menopausal women from the UK Biobank. We constructed and compared the “augmented” Cox model (incorporating the two PRS, known and novel predictors) with a “baseline” Cox model (incorporating the two PRS and known predictors) for risk prediction. Both of the two PRS were significant in the augmented Cox model ( $$p

Abstract Polygenic risk scores (PRS) are proposed for use in clinical and research settings for risk stratification. However, there are limited investigations on how different PRS diverge from each other in risk prediction of individuals. We compared two recently published PRS for each of three conditions, breast cancer, hypertension and dementia, to assess the stability of using these algorithms for risk prediction in a single large population. We used imputed genotyping data from the UK Biobank prospective cohort, limited to the White British subset. We found that: (1) 20% or more of SNPs in the first PRS were not represented in the more recent PRS for all three diseases, by the same SNP or a surrogate with R2 > 0.8 by linkage disequilibrium (LD). (2) Although the difference in the area under the receiver operating characteristic curve (AUC) obtained using the two PRS is hardly appreciable for all three diseases, there were large differences in individual risk prediction between the two PRS. For instance, for each disease, of those classified in the top 5% of risk by the first PRS, over 60% were not so classified by the second PRS. We found substantial discordance between different PRS for the same disease, indicating that individuals could receive different medical advice depending on which PRS is used to assess their genetic susceptibility. It is desirable to resolve this uncertainty before using PRS for risk stratification in clinical settings.

A polygenic risk score estimates the genetic risk of an individual for some disease or trait, calculated by aggregating the effect of many common variants associated with the condition. With the increasing availability of genetic data in large cohort studies such as the UK Biobank, inclusion of this genetic risk as a covariate in statistical analyses is becoming more widespread. Previously this required specialist knowledge, but as tooling and data availability have improved it has become more feasible for statisticians and epidemiologists to calculate existing scores themselves for use in analyses. While tutorial resources exist for conducting genome-wide association studies and generating of new polygenic risk scores, fewer guides exist for the simple calculation and application of existing genetic scores. This guide outlines the key steps of this process: selection of suitable polygenic risk scores from the literature, extraction of relevant genetic variants and verification of their quality, calculation of the risk score and key considerations of its inclusion in statistical models, using the UK Biobank imputed data as a model data set. Many of the techniques in this guide will generalize to other datasets, however we also focus on some of the specific techniques required for using data in the formats UK Biobank have selected. This includes some of the challenges faced when working with large numbers of variants, where the computation time required by some tools is impractical. While we have focused on only a couple of tools, which may not be the best ones for every given aspect of the process, one barrier to working with genetic data is the sheer volume of tools available, and the difficulty for a novice to assess their viability. By discussing in depth a couple of tools that are adequate for the calculation even at large scale, we hope to make polygenic risk scores more accessible to a wider range of researchers.

Abstract Background When using a continuous outcome measure in a randomised controlled trial (RCT), the baseline score should be measured in addition to the post-intervention score, and it should be analysed using the appropriate statistical analysis. Methods We derive the correlation between the change score and baseline score and show that there is always a correlation (usually negative) between the change score and baseline score. We discuss the following correlations and provide the mathematical derivations in the Appendix:Correlation between change score and baseline scoreCorrelation between change score and post scoreCorrelation between change score and average score. The setting here is a parallel, two-arm RCT, but the method discussed in this paper is applicable for any studies or trials that have a continuous outcome measure; it is not restricted to RCTs. Results We show that using the change score as the outcome measure does not address the problem of regression to the mean, nor does it take account of the baseline imbalance. Whether the outcome is change score or post score, one should always adjust for baseline using analysis of covariance (ANCOVA); otherwise, the estimated treat effect may be biased. We show that these correlations also apply when comparing two measurement methods using Bland-Altman plots. Conclusions The correlation between baseline and post-intervention scores can be derived using the variance sum law. We can then use the derived correlation to calculate the required sample size in the design stage. Baseline imbalance may occur in RCTs, and ANCOVA should be used to adjust for baseline in the analysis stage.

Objective To identify factors associated with hypertension control among treated middle-aged UK adults.Methods A cross-sectional population-based study including 99 468 previously diagnosed, treated hypertensives enrolled in the UK Biobank. Hypertension control was defined as systolic blood pressure 30 units per week compared with none), black ethnicity (OR 0.73, 95% CI 0.65 to 0.82 compared with white), obesity (OR 0.73, 95% CI 0.71 to 0.76 compared with normal body mass index). The strongest positive association with control was having ≥3 comorbidities (OR 2.09, 95% CI 1.95 to 2.23). Comorbidities associated with control included cardiovascular disease (OR 2.11, 95% CI 2.04 to 2.19), migraines (OR 1.68, 95% CI 1.56 to 1.81), diabetes (OR 1.32, 95% CI 1.27 to 1.36) and depression (OR 1.27, 95% CI 1.20 to 1.34).Conclusions In one of the largest population-based analyses of middle-aged adults with measured blood pressure, the majority of treated hypertensives were uncontrolled. Risk factors for hypertension were associated with a lower probability of control. Having a comorbidity was associated with higher probability of control, possibly due to more frequent interaction with the healthcare system and/or appropriate management of those at greater cardiovascular risk.

Introduction. Hypertension is a leading risk factor for cardiovascular mortality and an emerging public health concern in sub-Saharan Africa. Few studies have examined performance on the management of hypertension in this region, where the context may be distinct from other developing regions. Objectives. We aimed to determine the prevalence and correlates of hypertension, awareness, treatment, and control among adults in Botswana, a middle-income African country undergoing rapid demographic transition and with high HIV burden. Methods. In this 2014 cross-sectional survey of adults aged 15–69 years, information on sociodemographic characteristics, lifestyle behavior, and medical history was collected through in-person interviews and physical measurements (body mass index and triplicate blood pressure (BP)). Hypertension was defined as self-report of use of antihypertensives in the previous two weeks and/or having elevated BP (≥140/90 mmHg). Multivariable logistic regression was employed to explore factors associated with hypertension, awareness (report of previous diagnosis), treatment (antihypertensives), and control (BP

Objectives Early warning scores (EWS) alerting for in-hospital deterioration are commonly developed using routinely collected vital-sign data from the whole in-hospital population. As these in-hospital populations are dominated by those over the age of 45 years, resultant scores may perform less well in younger age groups. We developed and validated an age-specific early warning score (ASEWS) derived from statistical distributions of vital signs.Design Observational cohort study.Setting Oxford University Hospitals (OUH) July 2013 to March 2018 and Portsmouth Hospitals (PH) NHS Trust January 2010 to March 2017 within the Hospital Alerting Via Electronic Noticeboard database.Participants Hospitalised patients with electronically documented vital-sign observationsOutcome Composite outcome of unplanned intensive care unit admission, mortality and cardiac arrest.Methods and results Statistical distributions of vital signs were used to develop an ASEWS to predict the composite outcome within 24 hours. The OUH development set consisted of 2 538 099 vital-sign observation sets from 142 806 admissions (mean age (SD): 59.8 (20.3)). We compared the performance of ASEWS to the National Early Warning Score (NEWS) and our previous EWS (MCEWS) on an OUH validation set consisting of 581 571 observation sets from 25 407 emergency admissions (mean age (SD): 63.0 (21.4)) and a PH validation set consisting of 5 865 997 observation sets from 233 632 emergency admissions (mean age (SD): 64.3 (21.1)). ASEWS performed better in the 16–45 years age group in the OUH validation set (AUROC 0.820 (95% CI 0.815 to 0.824)) and PH validation set (AUROC 0.840 (95% CI 0.839 to 0.841)) than NEWS (AUROC 0.763 (95% CI 0.758 to 0.768) and AUROC 0.836 (95% CI 0.835 to 0.838) respectively) and MCEWS (AUROC 0.808 (95% CI 0.803 to 0.812) and AUROC 0.833 (95% CI 0.831 to 0.834) respectively). Differences in performance were not consistent in the elder age group.Conclusions Accounting for age-related vital sign changes can more accurately detect deterioration in younger patients.

We illustrate the approach of randomising treatments and compare it with the traditional approach of randomising patients, using a case study drawn from the authors’ experience in clinical trials. The setting is a double-blind parallel two-arm randomised controlled trial (RCT), but the method in this paper can be extended to single-blind, cross-over, or multi-arm RCTs.We propose the concept of two different levels of blinding: full blinding and partial blinding. We subsequently show how to maintain the maximal level of blinding. Using an example, we show that a pharmacist can be fully blinded if the investigational medical products (IMPs) that they prescribe (instead of patients) are randomised, and they can be partially blinded if they need to dispense replacement (i.e., surplus) IMPs. A small number of surplus IMPs is commonly required in a clinical trial to replace lost or damaged IMPs. We note that the concept of full blinding and partial blinding is different from double-blind trial, and the level of blinding is relevant in both single-blind and double-blind trials.A trial statistician needs to work closely with all parties in the design of the randomisation, including the pharmacist, the trial manager, and the manufacturer. We detail what should and should not be shown in the various documents that the trial statistician need to provide to the pharmacist and to the manufacturer. We provide template tables for these documents. Keywords: Randomisation, Blinding, Single-blind, Double-blind, Placebo, Randomised controlled trial (RCT), Investigational medical product (IMP), Pharmacist

Conventional methods for estimating cardiopulmonary variables usually require complex gas analyzers and the active co-operation of the patient. Therefore, they are not compatible with the crowded environment of the intensive care unit (ICU) or operating theatre, where patient co-operation is typically impossible. However, it is these patients that would benefit the most from accurate estimation of cardiopulmonary variables, because of their critical condition. This paper describes the results of a collaborative development between an anesthesiologists and biomedical engineers to create a compact and non-invasive system for the measurement of cardiopulmonary variables such as lung volume, airway dead space volume, and pulmonary blood flow. In contrast with conventional methods, the compact apparatus and non-invasive nature of the proposed method allow it to be used in the ICU, as well as in general clinical settings. We propose the use of a non-invasive method, in which tracer gases are injected into the patient's inspired breath, and the concentration of the tracer gases is subsequently measured. A novel breath-by-breath tidal ventilation model is then used to estimate the value of a patient's cardiopulmonary variables. Experimental results from an artificial lung demonstrate minimal error in the estimation of known parameters using the proposed method. Results from analysis of a cohort of 20 healthy volunteers (within the Oxford University Hospitals NHS Trust) show that the values of estimated cardiopulmonary variables from these subjects lies within the expected ranges. Advantages of this method are that it is non-invasive, compact, portable, and can perform analysis in real time with less than 1 min of acquired respiratory data.

Fibrinogen-fibrin degradation products (DR-70) are derived from tumor cells or metastases. Our previous study reported the diagnostic values in dogs with tumors, but no research has yet to be conducted to establish DR-70 as a prognostic marker. Herein, we investigated changes in DR-70 concentrations and disease courses in dogs with tumors. Overall survival time (OST) analysis was performed in 195 dogs with tumors, stratified with a recommended cut-off (1.514 µg/mL). Continual DR-70 measurements were performed during the medical interventions of 27 dogs with neoplasms. Clinical conditions and medical records were retrospectively reviewed. According to a cut-off value, dogs with plasma DR-70 concentrations above 1.514 µg/mL had shorter survival rates than those with concentrations below this threshold. In cases with complete or partial remission in response to treatment, the DR-70 concentration was decreased compared with that at the first visit, whereas it was increased in patients with disease progression. Our study suggested that changes in DR-70 concentration can be used as a prognostic biomarker for canine neoplasms. Furthermore, increased plasma DR-70 levels might be associated with shorter survival, and DR-70 concentrations may reflect responses to medical intervention.

The hippocampus is a brain region that is essential for the initial encoding of episodic memories. However, the consolidation of these memories is thought to occur in the neocortex, under guidance of the hippocampus, over the course of days and weeks. Communication between the hippocampus and the neocortex during hippocampal sharp wave-ripple oscillations is believed to be critical for this memory consolidation process. Yet, the synaptic and circuit basis of this communication between brain areas is largely unclear. To address this problem, we perform in vivo whole-cell patch-clamp recordings in the frontal neocortex and local field potential recordings in CA1 of head-fixed mice exposed to a virtual-reality environment. In mice trained in a goal-directed spatial task, we observe a depolarization in frontal principal neurons during hippocampal ripple oscillations. Both this ripple-associated depolarization and goal-directed task performance can be disrupted by chemogenetic inactivation of somatostatin-positive (SOM + ) interneurons. In untrained mice, a ripple-associated depolarization is not observed, but it emerges when frontal parvalbumin-positive (PV + ) interneurons are inactivated. These results support a model where SOM + interneurons inhibit PV + interneurons during hippocampal activity, thereby acting as a disinhibitory gate for hippocampal inputs to neocortical principal neurons during learning., Competing Interests: Competing interests statement:The authors declare no competing interest.

The intercropping of Morchella in pear orchards has important production value in improving the utilization rate and economic benefits of the orchard; however, there is little research on the intercropping model of pear- Morchella . In this study, metabolomics analysis found that compared with greenhouse cultivation, there were 104 and 142 metabolites significantly increased and decreased in the intercropping mode of M. sextelata , respectively. Among them, there was a significant accumulation of amino acids (phenylalanine, lysine, proline, citrulline, and ornithine), sugars (arabinitol and glucosamine), and organic acids (quinic acid, fumaric acid, and malic acid) related to the unique taste of Morchella in intercropping cultivation. In addition, research on the cultivation model using exogenous nutrient bags indicated that placing the density of six exogenous nutrient bags per square meter was most suitable for yield formation. Adding pear sawdust to the nutrient bags (PN) significantly increased the yield of morel per unit area. Moreover, soil microbial community analysis showed that fungal alpha diversity dramatically declined in PN-cultivated soil, which decreased the relative abundance of soil-borne fungal pathogens, including Fusarium and Aspergillus . Some beneficial soil bacteria abundance increased in the PN-used soil, such as Pedobacter , Pseudomonas, and Devosia . This study provides novel insights into the effects of intercropping on the internal quality of Morchella and enriches the theoretical knowledge on the consummation of the pear- Morchella model formation, further improving agricultural resource utilization efficiency and crop productivity.

Background: Arundinelleae is a small tribe within the Poaceae (grass family) possessing a widespread distribution that includes Asia, the Americas, and Africa. Several species of Arundinelleae are used as natural forage, feed, and raw materials for paper. The tribe is taxonomically cumbersome due to a paucity of clear diagnostic morphological characters. There has been scant genetic and genomic research conducted for this group, and as a result the phylogenetic relationships and species boundaries within Arundinelleae are poorly understood., Results: We compared and analyzed 11 plastomes of Arundinelleae, of which seven plastomes were newly sequenced. The plastomes range from 139,629 base pairs (bp) (Garnotia tenella) to 140,943 bp (Arundinella barbinodis), with a standard four-part structure. The average GC content was 38.39%, but varied in different regions of the plastome. In all, 110 genes were annotated, comprising 76 protein-coding genes, 30 tRNA genes, and four rRNA genes. Furthermore, 539 simple sequence repeats, 519 long repeats, and 10 hyper-variable regions were identified from the 11 plastomes of Arundinelleae. A phylogenetic reconstruction of Panicoideae based on 98 plastomes demonstrated the monophyly of Arundinella and Garnotia, but the circumscription of Arundinelleae remains unresolved., Conclusion: Complete chloroplast genome sequences can improve phylogenetic resolution relative to single marker approaches, particularly within taxonomically challenging groups. All phylogenetic analyses strongly support the monophyly of Arundinella and Garnotia, respectively, but the monophylly of Arundinelleae was not well supported. The intergeneric phylogenetic relationships within Arundinelleae require clarification, indicating that more data is necessary to resolve generic boundaries and evaluate the monophyly of Arundinelleae. A comprehensive taxonomic revision for the tribe is necessary. In addition, the identified hyper-variable regions could function as molecular markers for clarifying phylogenetic relationships and potentially as barcoding markers for species identification in the future., (© 2024. The Author(s).)

Purpose: The emergence of the SARS-CoV-2 Omicron variant has posed a significant global public health challenge. Elucidating the laboratory profiles of individuals infected with this variant is crucial for assessing organ damage. This study aimed to investigate the variations in liver function tests and their correlation with demographic characteristics and inflammatory markers in patients with early Omicron variant infections., Patients and Methods: A retrospective cohort study was conducted on 1133 mild or asymptomatic COVID-19 cases at Tianjin First Central Hospital. Data on age, gender, body mass index (BMI), and serum markers were collected and analyzed. Statistical analyses were performed using SPSS software, version 24.0., Results: Abnormal liver function parameters, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and total bilirubin (TBIL), were observed in 314 (27.71%) patients. "Hepatocellular type" was identified in 56 (4.94%) patients, "cholestatic type" in 185 (16.33%) patients, and "mixed type" in 73 (6.44%) patients. In the mixed group, we observed a pronounced elevation in the levels of ALT, AST, and GGT. Moreover, the hepatocellular group exhibited a statistically significant increase in AST and ALT concentrations relative to both the normal and cholestatic groups. Notably, the cholestatic group demonstrated a substantial increment in ALP levels. Males had a significantly higher prevalence of "abnormal liver enzyme markers" compared to females. Patients with "abnormal liver enzyme markers" exhibited significantly decreased immunoglobulin G (IgG) levels and elevated levels of inflammatory markers, including procalcitonin (PCT), interleukin-6 (IL6), as well as C-reactive protein (CRP) compared to normal group. Logistic regression analysis revealed that male gender and PCT levels were significantly associated with the risk of abnormal liver enzyme markers. Patients in hepatocellular group were likely accompanied with high CRP levels, whereas those in the cholestatic type were associated with high IL6 levels., Conclusion: Early Omicron infection might cause liver stress response. Elevated liver enzyme marker levels were correlated with age, gender, inflammatory factors, and IgG., Competing Interests: The author(s) report no conflicts of interest in this work., (© 2024 Cao et al.)

Depression is a significant mental health issue with extensive economic implications, and recent studies suggest it may be transmitted between individuals. However, the mechanisms of this contagion remain unclear, and the social buffering effect has been understudied. This research employs three rodent models, including stress crossover, cohabitation-induced, and non-contact induced depression contagion models, to explore these mechanisms. Here, we report that that naive mice cohabiting with depressed mice showed increased corticosterone levels and depressive behaviors, unlike those with stressed mice, who did not exhibit these changes and even mitigated desperation in stressed mice. Non-contact cohabitation did not produce significant behavioral differences, but exposure to bedding from depressed mice reduced sucrose preference in naive mice. This study introduces reliable models of depression contagion, suggesting it operates independently of stress transmission. The interplay between depression contagion and social buffering may vary in different contexts. These findings provide new insights into the mechanisms of depression contagion and potential strategies for preventing depressive disorders., (© 2024. The Author(s).)

Lignin is a key metabolite for terrestrial plants. Two types of aromatic amino acids, phenylalanine (Phe) and tyrosine (Tyr), serve as the precursors for lignin biosynthesis. In most plant species, Phe is deaminated by Phe ammonia-lyase (PAL) to initiate lignin biosynthesis, but in grass species, Phe and Tyr are deaminated by Phe/Tyr ammonia-lyase (PTAL). To understand the efficiency of PAL and PTAL, we used transgenic and non-transgenic Arabidopsis with PAL and crop-weedy rice hybrids (CWRH) with PTAL to analyze lignin-biosynthesis-associated metabolites. The transgenic plants overexpressed the exogenous 5-enolpyruvylshikimate-3-phosphate synthase ( EPSPS ) gene, whereas the non-transgenic plants normally expressed the endogenous EPSPS gene. Our results show significantly increased Phe/Tyr contents in transgenic Arabidopsis and CWRH plants, leading to substantially increased lignin and biomass. In addition, the PTAL pathway promotes a much greater proportion of increased lignin and biomass in transgenic CWRH than in transgenic Arabidopsis lineages. Evidently, more efficient lignin biosynthesis characterized the grass species possessing the PTAL pathway. These findings are important for a better understanding of the PAL and PTAL's functions in the phenylpropanoid metabolic pathways in the evolution of plant species. These findings also have great value for implications such as effective carbon fixation by enhancing lignin biosynthesis through genetic engineering of their key genes in appropriately selected plant species.

Midbrain organoids provide an innovative cellular source for transplantation therapies of neurodegenerative diseases. Here, we present a protocol for midbrain organoid-derived cell transplantation into a Parkinson's disease mouse model. We describe steps for midbrain organoid generation, single-cell suspension preparation, and cell transplantation. This approach is valuable for studying the efficacy of midbrain organoids as a potential cellular source for restoring motor function. For complete details on the use and execution of this protocol, please refer to Fu et al. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Three new species of Isodon (Lamiaceae) from China are described and illustrated, based on both morphological evidence and our recent phylogenomic studies of the genus. Isodonattenuatus , a herbaceous new species known only from the Fanjing Mountain, is shown to be sister to I.villosus , but they can be easily distinguished by leaf and inflorescence indumentum, calyx teeth shape and corolla tube morphology. Isodongongshanensis , a herbaceous new species collected from the Hengduan Mountains in southwest China, represents a distinct lineage within the genus. Isodonsukungii , a shrubby new species also endemic to the Hengduan Mountains, was previously misidentified as I.tenuifolius , but they are phylogenetically distantly related and differ in lamina size and margin, inflorescence type and corolla length and shape., Competing Interests: The authors have declared that no competing interests exist., (Ya-Ping Chen, Hua Peng, Alan J. Paton, Chun-Lei Xiang.)

Serine protease 50 (PRSS50/TSP50) is highly expressed in spermatocytes. Our study investigated its role in testicular development and spermatogenesis. Initially, PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes. To further explore this, we generated PRSS50 knockout ( Prss50 -/- ) mice ( Mus musculus ), which exhibited abnormal spermatid nuclear compression and reduced male fertility. Furthermore, dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50 -/- mice, accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells. Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and elevated levels of MAP kinase phosphatase 3 (MKP3), a specific ERK antagonist, potentially accounting for testicular dysplasia in adolescent Prss50 -/- mice. Taken together, these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis, with the MKP3/ERK signaling pathway playing a significant role in this process.

This study proposes a new method to evaluate the effectiveness of orebody grade estimations, drawing upon the analysis of existing evaluation methods for grade estimation. This new approach addresses factors such as uneven sampling and asymmetric estimation range, which are challenging to overcome with existing evaluation techniques. The core principle of this method involves documenting how frequently individual samples are used during grade estimation and calculating the total distance weights for each sample. Subsequently, the usage frequency and total weight of the samples are standardized, and these standardized values are weighted based on the sample grades. A comparison is made between the weighted sample grades and the estimated grades, with the closeness between the two serving as a metric for assessing the effectiveness of the estimation. This study compares the new evaluation method to the direct comparison and cross-validation methods, examining the effectiveness of grade estimation using the inverse distance weighting (IDW) method. The findings revealed that: (1) The new evaluation method theoretically accounts for the systematic deviation between the statistical measures of estimated and sample grades resulting from uneven sample distribution, offering a fresh approach for enhancing the effectiveness of orebody grade estimation. (2) In the grade estimation of experimental Fe samples, the frequency of usage and the sum of distance weights were unequal. This inequality significantly contributes to the systematic deviation between the estimated and sample grades. (3) Comparing the new evaluation method to others confirms the stability and reliability of the new approach for evaluating the effectiveness of orebody grade estimation. This novel method demonstrates theoretical advantages and practical utility. (4) The deviation between the estimated grades and the statistical results of sample grades is influenced by the distribution pattern of sample grades, the spatial relationship between samples and estimation blocks, and the inherent systematic error associated with the IDW method. This systematic error cannot be overlooked., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Effective lineage-specific differentiation is essential to fulfilling the great potentials of human pluripotent stem cells (hPSCs). In this report, we investigate how modulation of medium pH and associated metabolic changes influence mesendoderm differentiation from hPSCs. We show that daily medium pH fluctuations are critical for the heterogeneity of cell fates in the absence of exogenous inducers. Acidic environment alone leads to cardiomyocyte generation without other signaling modulators. In contrast, medium alkalinization is inhibitory to cardiac fate even in the presence of classic cardiac inducers. We then demonstrate that acidic environment suppresses glycolysis to facilitate cardiac differentiation, while alkaline condition promotes glycolysis and diverts the differentiation toward other cell types. We further show that glycolysis inhibition or AMPK activation can rescue cardiac differentiation under alkalinization, and glycolysis inhibition alone can drive cardiac cell fate. This study highlights that pH changes remodel metabolic patterns and modulate signaling pathways to control cell fate., Competing Interests: Declaration of interests W.L. and G.C. filed a patent application based on cardiomyocyte differentiation that is induced by acidic pH., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Salviapenghuana , a new species from Guizhou Province of southwestern China, is described and illustrated. Morphologically, Salviapenghuana is similar to S.filicifolia , but can be easily distinguished from the latter by ovate-lanceolate bracts, purple corolla, and foot-shaped fused lower arms of connective. In addition, S.penhuana is morphologically similar to S.cavaleriei , but differs by having 3-4-pinnate leave, ovate-lanceolate bracts, puberulent calyx, and longer upper arms of connective. Based on the fibril root, small calyx and corolla, and completely reduced posterior thecae, S.penghuana should be placed in section Sobiso of subg. Glutinaria., Competing Interests: The authors have declared that no competing interests exist., (Feng-Jin Qiu, Deng-Li Yu, Hong-Bo Lan, Ming-Tai An, Yan-Fei Geng, Chun-Lei Xiang, Guo-Xiong Hu.)

Phlomoidesbomiensis , a new species in Bomi County, Xizang, China, was described and illustrated. In addition, Phlomoideslongidentata , previously only known from Nepal and Bhutan, is newly recorded from Dingri County, Xizang, China. The phylogenetic placement of both species within the genus was analysed using nine plastid DNA markers ( atpB-rbcL , psbA-trnH , rpl16 , rpl32-trnL , rps16 , trnK , trnL-trnF , trnS-trnG , trnT-trnL ). Both species have brown-black trichomes inside the upper corolla lip and nested within the same subclade of Clade II. A diagnostic key to the Phlomoides species belonging to this subclade is provided., Competing Interests: The authors have declared that no competing interests exist., (Yue Zhao, Ya-Ping Chen, Rui-Zhu Bai, Colin A. Pendry, Alexander P. Sukhorukov, Chun-Lei Xiang.)

Background: Increasing evidence supports the association between impaired oral health and elevated mortality. However, there is currently a lack of research on the impact of tooth loss and periodontal disease on survival outcomes in cancer survivors. This study aims to clarify the effect of tooth loss and periodontitis on all-cause mortality on cancer survivors., Methods: The clinical data of cancer survivors were collected from National Health and Nutrition Examination Survey (NHANES) 1999-2018. Mortality data were obtained by linking to records in the National Death Index until December 31, 2019. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal threshold for discriminating mortality based on the number of teeth lost. Kaplan-Meier survival curves and Cox regression analysis were performed to calculate hazard ratios (HRs) and 95 % confidence intervals (95 % CI) for tooth loss and periodontitis., Results: A total of 3271 cancer survivors were assessed for tooth loss status, while 1267 patients were evaluated for periodontitis status. The prevalence of any tooth loss and CDC-AAP periodontitis was 83.5 % and 47.2 %, respectively. The ROC curve showed the cut-off point of tooth loss for predicting mortality is > 5. Cancer survivors with tooth loss>5 had significantly lower bone density (1.06 vs. 1.13 g/cm 2 , P  < 0.001), elevated C-reactive protein level (0.3 vs. 0.18 mg/dL, P  < 0.001), and a trend of lower lean body mass (46.9 vs. 47.6 kg, P  = 0.093). Besides, cancer survivors with severe periodontitis also exhibited elevated C-reactive protein level (0.34 vs. 0.21 mg/dL, P  = 0.033). All-cause mortality significantly increased in cancer survivors with either tooth loss>5 (HR = 1.290, P  = 0.001) or severe CDC-AAP periodontitis (HR = 1.682, P  = 0.016) in the multivariate Cox regression analysis., Conclusion: Tooth loss and periodontitis are strong risk factors for reduced overall survival in cancer survivors. Cancer survivors should emphasize diligent oral hygiene and consistent dental check-ups to optimize long-term oral health. The causal relationship between oral health and survival rates in cancer survivors requires further validation through randomized controlled trials., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Herba Patriniae and Coix seed (HC) constitute a widely utilized drug combination in the clinical management of colorectal cancer (CRC) that is known for its diuretic, anti-inflammatory, and swelling-reducing properties. Although its efficacy has been demonstrated in a clinical setting, the active compounds and their mechanisms of action in CRC treatment remain to be fully elucidated., Aim: To identify the active, CRC-targeting components of HC and to elucidate the mechanisms of action involved., Methods: Active HC components were identified and screened using databases. Targets for each component were predicted. CRC-related targets were obtained from human gene databases. Interaction targets between HC and CRC were identified. A "drug-ingredient-target" network was created to identify the core components and targets involved. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to elucidate the key pathways involved. Molecular docking between core targets and key components was executed. In vitro experiments validated core monomers., Results: Nineteen active components of HC were identified, with acacetin as the primary active compound. The predictive analysis identified 454 targets of the active compounds in HC. Intersection mapping with 2685 CRC-related targets yielded 171 intervention targets, including 30 core targets. GO and KEGG analyses indicated that HC may influence the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Molecular docking showed that acacetin exhibited an optimal interaction with AKT1 , identifying PI3K , AKT , and P53 as key genes likely targeted by HC during CRC treatment. Acacetin inhibited HT-29 cell proliferation and migration, as well as promoted apoptosis, in vitro . Western blotting analysis revealed increased p53 and cleaved caspase-3 expression and decreased levels of p-PI3K , p-Akt , and survivin, which likely contributed to CRC apoptosis., Conclusion: Acacetin, the principal active compound in the HC pair, inhibited the proliferation and migration of HT-29 cells and promoted apoptosis through the PI3K/Akt/p53 signaling pathway., Competing Interests: Conflict-of-interest statement: Authors have no conflicts of interest to declare., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Considering that changes in the choroidal thickness are closely related to ocular growth, we studied the choroidal thickness (CT) and the blood flow features in children with unilateral myopic anisometropia (UMA) as well as investigating the relationship between choroidal changes and myopia., Methods: Subjective refractive, axial length (AL), and biometric parameters were measured in 98 UMA children (age: 8-15 years). CT and choroidal blood-flow features, including the choroidal vessel volume (CVV), choroidal vascularity index (CVI), and choriocapillaris perfusion area (CCPA), were measured through swept-source optical coherence tomography angiography. The macular region was categorized into four concentric circles of diameters 0-1 mm (central fovea), 1-3 mm (parafovea), 3-6 mm (perifovea), and 6-9 mm (extended), and further categorized into superior (S), inferior (I), temporal (T), and nasal (N) quadrants., Results: The aforementioned four regions of myopic eyes displayed significantly lower CT, CVV, and CVI than those of non-myopic eyes. CCPA changes differed across different regions of both the eyes (parts of N and T quadrants). There was an inverse association between CT and the interocular AL difference (central and other regions S, T quadrant). No correlation was noted between CVV and CVI with interocular AL difference. CT and CVV were positively correlated in the 0-6-mm macular region of myopic eyes (Spearman correlation coefficient = 0.763, P < 0.001)., Conclusions: In UMA children, CCT and blood flow may be related to myopia progression. A robust correlation between CT and CVV in the 0-6-mm macular region and reduced CT and diminished blood flow indicated an association with myopia., (© 2024. The Author(s).)

Learning and memory impairment (LMI), a common degenerative central nervous system disease. Recently, more and more studies have shown that Ganoderma lucidum (GL) can improve the symptoms of LMI. The active ingredients in GL and their corresponding targets were screened through TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and BATMAN-TCM (Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine) databases, and the potential LMI targets were searched for through GeneCard (GeneCards Human Gene Database) and DrugBank. Then, we construct a 'main active ingredient-target' network and a protein-protein interaction (PPI) network diagram.The GO (Gene Ontology) functional enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway annotation analysis were performed on the common targets through DAVID (Database for Annotation Visualization and Integrated Discovery) to clarify the potential molecular mechanism of action of active ingredients in GL. The tumor necrosis factor (TNF) protein was verified by Western blot; Twenty one active ingredients in GL and 142 corresponding targets were screened out, including 59 targets shared with LMI. The 448 biological processes shown by the GO functional annotation results and 55 signal pathways shown by KEGG enrichment analysis were related to the improvement of LMI by GL, among which the correlation of Alzheimer's disease pathway is the highest, and TNF was the most important protein; TNF can improve LMI. GL can improve LMI mainly by 10 active ingredients in it, and they may play a role by regulating Alzheimer's disease pathway and TNF protein., (© 2024 The Author(s).)

Background: This study aimed to investigate alterations in serum markers [creatine kinase-MB (CKMB), cardiac troponin T (cTnT), myoglobin (Myo), B-type natriuretic peptide (BNP), D-dimer (DD), procalcitonin (PCT) and interleukin-6 (IL6)] in early Omicron variant infection and analyzed their correlation with clinical parameters., Methods: Retrospective analysis of 1,138 mild/asymptomatic cases at Tianjin First Central Hospital, including age, gender, serum markers and nucleic acid test results. Statistical analysis used SPSS software, version 24.0., Results: Elevated cTnT, BNP (125-400), and DD (0.55-1.10) levels were prevalent at 12.92%, 15.64%, and 14.50%, respectively. Females had significantly higher proportions with slightly elevated BNP (19.34%) and DD (19.69%) levels. Patients over 35 had a higher proportion of slight elevation in BNP (20.00%). Abnormal levels of serum markers were significantly associated with older age, increased PCT and IL6 levels, as well as delayed nucleic acid clearance. Additionally, levels of immunoglobulin G (IgG) were notably reduced in these cases. Patients with prolonged nucleic acid clearance (>14 days) had higher BNP and DD levels upon admission. Logistic regression identified PCT (OR = 237.95) as the most significant risk factor for abnormal serum markers for cardiovascular system injury., Conclusion: Early Omicron infection might do subclinical damage to the cardiovascular system. Elevated cTnT, BNP and DD levels were correlated with age, gender, inflammatory factors, and IgG. Notably, high PCT level emerged as the most robust predictor of abnormal serum biomarkers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Cao, Xie, Yi, Liu, Zhang, Yue, Li, Zhou and Mu.)

Somatic variation is a major type of genetic variation contributing to human diseases including cancer. Of the vast quantities of somatic variants identified, the functional impact of many somatic variants, in particular the missense variants, remains unclear. Lack of the functional information prevents the translation of rich variation data into clinical applications. We previously developed a method named Ramachandran Plot-Molecular Dynamics Simulations (RP-MDS), aiming to predict the function of germline missense variants based on their effects on protein structure stability, and successfully applied to predict the deleteriousness of unclassified germline missense variants in multiple cancer genes. We hypothesized that regardless of their different genetic origins, somatic missense variants and germline missense variants could have similar effects on the stability of their affected protein structure. As such, the RP-MDS method designed for germline missense variants should also be applicable to predict the function of somatic missense variants. In the current study, we tested our hypothesis by using the somatic missense variants in TP53 as a model. Of the 397 somatic missense variants analyzed, RP-MDS predicted that 195 (49.1%) variants were deleterious as they significantly disturbed p53 structure. The results were largely validated by using a p53-p21 promoter-green fluorescent protein (GFP) reporter gene assay. Our study demonstrated that deleterious somatic missense variants can be identified by referring to their effects on protein structural stability., (© The Author(s) 2024. Published by Oxford University Press.)

Cellular electrophysiology is the foundation of many fields, from basic science in neurology, cardiology, oncology to safety critical applications for drug safety testing, clinical phenotyping, etc. Patch-clamp voltage clamp is the gold standard technique for studying cellular electrophysiology. Yet, the quality of these experiments is not always transparent, which may lead to erroneous conclusions for studies and applications. Here, we have developed a new computational approach that allows us to explain and predict the experimental artefacts in voltage-clamp experiments. The computational model captures the experimental procedure and its inadequacies, including: voltage offset, series resistance, membrane capacitance and (imperfect) amplifier compensations, such as series resistance compensation and supercharging. The computational model was validated through a series of electrical model cell experiments. Using this computational approach, the artefacts in voltage-clamp experiments of cardiac fast sodium current, one of the most challenging currents to voltage clamp, were able to be resolved and explained through coupling the observed current and the simulated membrane voltage, including some typically observed shifts and delays in the recorded currents. We further demonstrated that the typical way of averaging data for current-voltage relationships would lead to biases in the peak current and shifts in the peak voltage, and such biases can be in the same order of magnitude as those differences reported for disease-causing mutations. Therefore, the presented new computational pipeline will provide a new standard of assessing the voltage-clamp experiments and interpreting the experimental data, which may be able to rectify and provide a better understanding of ion channel mutations and other related applications., Competing Interests: Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Education, cognition, and intelligence are associated with cholelithiasis occurrence, yet which one has a prominent effect on cholelithiasis and which cardiometabolic risk factors mediate the causal relationship remain unelucidated., Aim: To explore the causal associations between education, cognition, and intelligence and cholelithiasis, and the cardiometabolic risk factors that mediate the associations., Methods: Applying genome-wide association study summary statistics of primarily European individuals, we utilized two-sample multivariable Mendelian randomization to estimate the independent effects of education, intelligence, and cognition on cholelithiasis and cholecystitis (FinnGen study, 37041 and 11632 patients, respectively; n = 486484 participants) and performed two-step Mendelian randomization to evaluate 21 potential mediators and their mediating effects on the relationships between each exposure and cholelithiasis., Results: Inverse variance weighted Mendelian randomization results from the FinnGen consortium showed that genetically higher education, cognition, or intelligence were not independently associated with cholelithiasis and cholecystitis; when adjusted for cholelithiasis, higher education still presented an inverse effect on cholecystitis [odds ratio: 0.292 (95%CI: 0.171-0.501)], which could not be induced by cognition or intelligence. Five out of 21 cardiometabolic risk factors were perceived as mediators of the association between education and cholelithiasis, including body mass index (20.84%), body fat percentage (40.3%), waist circumference (44.4%), waist-to-hip ratio (32.9%), and time spent watching television (41.6%), while time spent watching television was also a mediator from cognition (20.4%) and intelligence to cholelithiasis (28.4%). All results were robust to sensitivity analyses., Conclusion: Education, cognition, and intelligence all play crucial roles in the development of cholelithiasis, and several cardiometabolic mediators have been identified for prevention of cholelithiasis due to defects in each exposure., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: The human microbiota plays a key role in cancer diagnosis, pathogenesis, and treatment. However, osteosarcoma-associated oral microbiota alterations have not yet been unraveled. The aim of this study was to explore the characteristics of oral microbiota in osteosarcoma patients compared to healthy controls, and to identify potential microbiota as a diagnostic tool for osteosarcoma., Methods: The oral microbiota was analyzed in osteosarcoma patients (n = 45) and matched healthy controls (n = 90) using 16S rRNA MiSeq sequencing technology., Results: The microbial richness and diversity of the tongue coat were increased in osteosarcoma patients as estimated by the abundance-based coverage estimator indices, the Chao, and observed operational taxonomy units (OTUs). Principal component analysis delineated that the oral microbial community was significant differences between osteosarcoma patients and healthy controls. 14 genera including Rothia, Halomonas, Rhodococcus, and Granulicatella were remarkably reduced, whereas Alloprevotella, Prevotella, Selenomonas, and Campylobacter were enriched in osteosarcoma. Eventually, the optimal four OTUs were identified to construct a microbial classifier by the random forest model via a fivefold cross-validation, which achieved an area under the curve of 99.44% in the training group (30 osteosarcoma patients versus 60 healthy controls) and 87.33% in the test group (15 osteosarcoma patients versus 30 healthy controls), respectively. Notably, oral microbial markers validated strong diagnostic potential distinguishing osteosarcoma patients from healthy controls., Conclusion: This study comprehensively characterizes the oral microbiota in osteosarcoma and reveals the potential efficacy of oral microbiota-targeted biomarkers as a noninvasive biological diagnostic tool for osteosarcoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Li, Wang, Zhang, Ren and Wang.)

Cortisol is a key stress biomarker in humans and animals, including fishes. In aquafarming, stress monitoring using cortisol quantification can help to optimize aquaculture practices for welfare and productivity enhancement. However, most current methods for cortisol detection rely on invasive tissue sampling. In this work, we developed a gold nanoparticle (AuNP)-based cortisol sensor to address the demand of detecting picomolar ranges of cortisol from complex fish tank water matrices as a non-invasive alternative for more effective stress monitoring. We first identified a DNA aptamer with effective binding to cortisol and then conjugated the thiol-labelled aptamer to AuNPs together with a blocker molecule (CALNN) to form an Au-Apt-CALNN conjugate that is stable in fish tank water. The cortisol detection principle is based on magnesium chloride (MgCl 2 )-induced particle aggregation, where the cortisol-bound aptamer on the AuNPs folds into a tertiary structure and provides greater protection for Au-Apt-CALNN against MgCl 2 -induced aggregation due to steric stabilization. At an optimum MgCl 2 concentration, the differential stability of particles with and without cortisol binding offers a limit of detection (LOD) of 100 pM for cortisol within a 35 min reaction. The aptasensor has been validated on recirculating aquaculture system (RAS) fish tank water samples by the HPLC method and was able to detect changes in water cortisol induced by two different stress paradigms. This on-site deployable and non-invasive sensor offers opportunities for more efficient and real-time fish stress monitoring for the optimization of aquaculture practices.

The occurrence of wound infection following a Caesarean section procedure poses a substantial clinical obstacle. Transcutaneous Electrical Nerve Stimulation (TENS) has been identified as a promising supplementary treatment option for improving the healing process and decreasing the incidence of infections. This study assessed the efficacy of TENS therapy in the postoperative care of patients who have had Caesarean section. We randomly assigned a total of 108 women who had Caesarean sections to either a TENS group (n = 54) or control (n = 54). The TENS therapy was provided twice daily for a duration of 30 min for the period of 14 days following the surgery. The main measure of interest in this study was the occurrence of wound infection during 30-day period. Additionally, secondary measures included the rate of wound healing, levels of pain experienced and level of patient satisfaction. In comparison to the control (22.2%, p < 0.05), the TENS group had notably reduced occurrence of wound infection, with the rate of 7.4%. TENS group had superior wound healing results, as measured by REEDA scale, at 7 days (2.1 ± 0.8 vs. 2.5 ± 1.0, p < 0.04), 14 days (1.2 ± 0.5 vs. 1.9 ± 0.7, p < 0.05) and 30 days (0.3 ± 0.5 vs. 0.7 ± 0.6, p < 0.05). Furthermore, TENS group had reduced pain levels on the Visual Analog Scale (VAS) at all evaluation intervals (p < 0.05). TENS group exhibited significantly higher levels of patient satisfaction, as evidenced by 64.8% of participants rating high satisfaction, in contrast to 40.7% in the control group (p < 0.05). The incidence of adverse effects was found to be minor, as indicated by a skin irritation rate of 3.7% and reported discomfort rate of 1.9% at the electrode location. TENS therapy effectively decreased the occurrence of post-Caesarean wound infections, expedited the healing process and enhanced pain control. This treatment was well-received by patients and had little negative consequences. The aforementioned results provided evidence in favour of incorporating TENS into post-Caesarean care regimens, which may have significant consequences for improving patient outcomes and maximizing healthcare resources., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Styles and stigmas are crucial components of the fertilization process that allows a pear tree to bear fruit. The information regarding the development mechanism of pear style and stigma is still unclear. Our results demonstrated that IAA, ABA, and BR are significantly increased at 1 DBF, while JA is decreased at 5 DBF. The fructose and starch contents significantly increased at 1 DBF when the style with stigma was ready for pollination. Transcriptome and DNA methylation analysis showed 8087 DEGs and 3771 DMRs were enriched in plant hormones biosynthesis, carbohydrate biosynthesis and metabolism, and TFs in 1 DBF as compared with 7 DBF. The CHH methylation type of DMRs accounts for 84.75%. Most DMRs of CHH upregulated in 1 DBF vs. 7 DBF. This study found for the first time that transcription factor ERFs and DNA methylation are involved in regulating the growth and development of fruit plant style and stigma., Competing Interests: The authors declare that there is no conflict to interest., (© 2024 The Author(s).)

The hippocampus is thought to provide the brain with a cognitive map of the external world by processing various types of spatial information. To understand how essential spatial variables such as direction, position, and distance are transformed along its circuits to construct this global map, we perform single-photon widefield microendoscope calcium imaging in the dentate gyrus and CA3 of mice freely navigating along a narrow corridor. We find that spatial activity maps in the dentate gyrus, but not in CA3, are correlated after aligning them to the running directions, suggesting that they represent the distance traveled along the track in egocentric coordinates. Together with population activity decoding, our data suggest that while spatial representations in the dentate gyrus and CA3 are anchored in both egocentric and allocentric coordinates, egocentric distance coding is more prevalent in the dentate gyrus than in CA3, providing insights into the assembly of the cognitive map., Competing Interests: Soham Saha is a co-founder of MedInsights SAS, Paris., (© 2024 The Author(s).)

Psoriasis is an immune-mediated, chronic, relapsing, inflammatory, systemic disease induced by individual-environmental interactions, and is often lifelong because of the difficulty of treatment. In recent years, a variety of targeted therapies, including biologics, have improved the lesions and quality of life of most psoriasis patients, but they still do not address the problem of relapse and may be associated with decreased efficacy or adverse events such as infections over time. Therefore, there is an urgent need for breakthroughs in psoriasis treatment and in relapse-delaying and non-pharmacologic strategies, and stem cell therapy for psoriasis has emerged. In recent years, research on stem cell therapy for psoriasis has received a lot of attention, however, there is no reference standard as well as consensus in this field of research. Therefore, according to the latest consensus and guidelines, combined with relevant literature reports, clinical practice experience and the results of discussions with experts, this consensus specifies the types of stem cells commonly used in the treatment of psoriasis, the methods, dosages, and routes of stem cell therapy for psoriasis, as well as the clinical evaluations (efficacy and safety) of stem cell therapy for psoriasis. In addition, this consensus also provides normative standards for the processes of collection, preparation, preservation and quality control of stem cells and their related products, as well as recommendations for the management of stem cells during infusion for the treatment of psoriasis. This consensus provides the latest specific reference standards and practice guidelines for the field of stem cell therapy for psoriasis.

Objective: Screening and predicting potential targets for gastrodin antioxidant stress based on network pharmacology methods, and exploring the effect of gastrodin on lead acetate induced oxidative stress in PC12 cells through cell experiments., Methods: Through the Pharmaper database Predict the target of action of gastrodin. Through OMIM and GeneCards to collect oxidative stress targets from database, and intersect with drug targets to obtain drug disease intersection targets; Construct a PPI network diagram using the STRING database. Perform GO enrichment analysis and KEGG pathway enrichment analysis on intersection targets through the DAVID platform. Lead acetate (PbAc) exposure was used to establish a lead poisoning cell model, and intracellular ROS levels, ALB, AKT1, and Caspase-3 levels were measured., Results: A total of 288 targets of gastrodin action, 638 targets related to oxidative stress, and 62 drug disease intersection targets were obtained, among which core targets such as ALB, AKT1, CASP3 may be closely related to oxidative stress. KEGG pathway analysis showed that gastrodin antioxidant stress mainly involved in lipid, cancer pathway and other signaling pathways. The results of the cell experiment showed that 50 μM is the optimal effective concentration for PbAc induced ROS production in PC12 cells. Gastrodin significantly increased the ROS content of PC12 cells treated with PbAc, Upregulation of ALB expression and downregulation of AKT1 and CASP3 expression., Conclusions: Gastrodin may alleviate PbAc-induced ROS in PC12 cells, indicating potential protective effects against oxidative stress. Further studies are needed to confirm these findings and explore the underlying mechanisms., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

This study examined the impact of brief mindfulness meditation (BMM) training on attention function and dispositional mindfulness in young males. 126 male participants aged 18-26 from the security industry were recruited, with 66 participants (M = 22.84, SD = 2.41) undergoing 4-week mindfulness meditation training and 60 participants (M = 23.07, SD = 2.29) in the active control group. The intervention was integrated into the participants' schedules. Measures included Five Facets Mindfulness Questionnaires (FFMQ), concentration and assignment attention tasks, Attention Network Test (ANT), and saliva cortisol concentration. Findings indicate that brief mindfulness meditation training led to significant improvements in participants' FFMQ scores), with marginally significant enhancements in the executive control network. However, it had no discernible effect on alertness and orientation networks. Additionally, brief mindfulness meditation training enhanced attention allocation to light stimulation and prolonged individual attention. Surprisingly, there was no observed decrease in saliva cortisol concentration among meditation training participants. However, this study did not find a decrease in saliva cortisol concentration in the brief mindfulness meditation group. In conclusion, this study highlights the potential of a 4-week brief mindfulness meditation training program to enhance dispositional mindfulness and specific aspects of attention function in young men, offering practical insights into the benefits of mindfulness meditation practices for this demographic., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Electroacupuncture (EA) has been shown to facilitate brain plasticity-related functional recovery following ischemic stroke. The functional magnetic resonance imaging technique can be used to determine the range and mode of brain activation. After stroke, EA has been shown to alter brain connectivity, whereas EA's effect on brain network topology properties remains unclear. An evaluation of EA's effects on global and nodal topological properties in rats with ischemia reperfusion was conducted in this study., Methods and Results: There were three groups of adult male Sprague-Dawley rats: sham-operated group (sham group), middle cerebral artery occlusion/reperfusion (MCAO/R) group, and MCAO/R plus EA (MCAO/R + EA) group. The differences in global and nodal topological properties, including shortest path length, global efficiency, local efficiency, small-worldness index, betweenness centrality (BC), and degree centrality (DC) were estimated. Graphical network analyses revealed that, as compared with the sham group, the MCAO/R group demonstrated a decrease in BC value in the right ventral hippocampus and increased BC in the right substantia nigra, accompanied by increased DC in the left nucleus accumbens shell (AcbSh). The BC was increased in the right hippocampus ventral and decreased in the right substantia nigra after EA intervention, and MCAO/R + EA resulted in a decreased DC in left AcbSh compared to MCAO/R., Conclusion: The results of this study provide a potential basis for EA to promote cognitive and motor function recovery after ischemic stroke., (© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Phlomoides , with 150-170 species, is the second largest and perhaps most taxonomically challenging genus within the subfamily Lamioideae (Lamiaceae). With about 60 species, China is one of three major biodiversity centers of Phlomoides . Although some Phlomoides species from China have been included in previous molecular phylogenetic studies, a robust and broad phylogeny of this lineage has yet to be completed. Moreover, given the myriad new additions to the genus, the existing infrageneric classification needs to be evaluated and revised. Here, we combine molecular and morphological data to investigate relationships within Phlomoides , with a focus on Chinese species. We observed that plastid DNA sequences can resolve relationships within Phlomoides better than nuclear ribosomal internal and external transcribed spacer regions (nrITS and nrETS). Molecular phylogenetic analyses confirm the monophyly of Phlomoides , but most previously defined infrageneric groups are not monophyletic. In addition, morphological analysis demonstrates the significant taxonomic value of eight characters to the genus. Based on our molecular phylogenetic analyses and morphological data, we establish a novel section Notochaete within Phlomoides , and propose three new combinations as well as three new synonyms. This study presents the first molecular phylogenetic analyses of Phlomoides in which taxa representative of the entire genus are included, and highlights the phylogenetic and taxonomic value of several morphological characters from species of Phlomoides from China. Our study suggests that a taxonomic revision and reclassification for the entire genus is necessary in the future., Competing Interests: The authors declare no conflict of interest., (© 2024 Kunming Institute of Botany, Chinese Academy of Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)