Search

BACKGROUND: and OBJECTIVE: Motor control of the upper extremity during unilateral and bimanual functional tasks and functional change during daily activities were evaluated in patients with stroke treated with modified constraint-induced movement therapy (mCIMT). METHODS: In a pre-post randomized, controlled trial, 30 stroke patients received 2 hours of mCIMT or traditional rehabilitation (TR) for 3 weeks. Motor control of the upper extremity was evaluated using kinematic analysis in unilateral and bilateral tasks. Kinematic variables included spatial and temporal movement efficiency and type of movement control (preplanned control, representing well-learned movement, or feedback-guided control). Functional outcomes were evaluated using the Motor Activity Log (MAL) and the Functional Independence Measure (FIM). RESULTS: Patients receiving mCIMT showed more temporally (P = .013) and spatially (P = .011) efficient movement and more preplanned movement control (P = .009) during the bimanual task, and greater gains in FIM (P = .004) and MAL scores (amount of use: P < .0001, and quality of movement: P = .012) than patients in the TR group. Patients receiving mCIMT produced more ballistic/preplanned reaching movement than did patients receiving TR (P = .023) during the unilateral task; but there were no group differences in temporal or spatial efficiency in unilateral task performance. CONCLUSIONS: Relative to TR, mCIMT produced a greater improvement in functional performance and motor control. Improvement of motor control after mCIMT was based on improved spatial and temporal efficiency, apparently more salient during bimanual rather than unilateral task performance. This suggests that bilateral task performance should potentially be emphasized in kinematic study of changes in motor control after mCIMT. [ABSTRACT FROM AUTHOR]

Rechargeable batteries have been indispensable for various portable devices, electric vehicles, and energy storage stations. The operation of rechargeable batteries at low temperatures has been challenging due to increasing electrolyte viscosity and rising electrode resistance, which lead to sluggish ion transfer and large voltage hysteresis. Advanced electrolyte design and feasible electrode engineering to achieve desirable performance at low temperatures are crucial for the practical application of rechargeable batteries. Herein, the failure mechanism of the batteries at low temperature is discussed in detail from atomic perspectives, and deep insights on the solvent-solvent, solvent-ion, and ion-ion interactions in the electrolytes at low temperatures are provided. The evolution of electrode interfaces is discussed in detail. The electrochemical reactions of the electrodes at low temperatures are elucidated, and the approaches to accelerate the internal ion diffusion kinetics of the electrodes are highlighted. This review aims to deepen the understanding of the working mechanism of low-temperature batteries at the atomic scale to shed light on the future development of low-temperature rechargeable batteries., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The N7-methylguanosine (m7G) methyltransferase Mettl1 has been recently implicated in cardiac repair and fibrosis. In this study we investigated the role of Mettl1 in mouse cardiomyocytes injury and the underlying mechanisms. Cardiac ischemia/reperfusion (I/R) I/R model was established in mice by ligation of the left anterior descending coronary artery (LAD) for 45 min followed by reperfusion for 24 h. We showed the mRNA and protein levels of Mettl1 were significantly upregulated in mouse I/R hearts and H 2 O 2 -treated neonatal mouse cardiomyocytes (NMCMs). Mettl1 knockdown markedly ameliorated cardiac I/R injury, evidenced by decreased infarct size, apoptosis, and improved cardiac function. Overexpression of Mettl1 triggered cardiomyocytes apoptosis in vivo and in vitro. By performing RNA sequencing combined with m7G methylated RNA sequencing in Mettl1-overexpressing mouse hearts, we revealed that Mettl1 catalyzed m7G modification of the deubiquitinase cylindromatosis (CYLD) mRNA to increase the expression of CYLD, which enhanced the stability of P53 via abrogating its ubiquitination degradation. Vice versa, P53 served as a transcriptional factor to positively regulate Mettl1 expression during I/R injury. Knockdown of CYLD mitigated cardiomyocytes apoptosis induced by Mettl1 overexpression or oxidative stress. From the available drug-targets databases and literature, we identified 4 small molecule inhibitors of m7G modification. Sinefungin, one of the Mettl1 inhibitors exerted profound protection against cardiac I/R injury in vivo and in vitro. Collectively, this study has identified Mettl1 as a key regulator of cardiomyocyte apoptosis, and targeting the Mettl1-CYLD-P53 positive feedback circuit may represent a novel therapeutic avenue for alleviating cardiac I/R injury., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background: The cardiometabolic index (CMI) is a novel metric for assessing cardiometabolic health and type 2 diabetes mellitus (DM), yet its relationship with insulin resistance (IR) and prediabetes (preDM) is not well-studied. There is also a gap in understanding the nonlinear associations between CMI and these conditions. Our study aimed to elucidate these associations., Methods: We included 13,142 adults from the National Health and Nutrition Examination Survey (NHANES) 2007-2020. CMI was calculated by multiplying the triglyceride-to-high density lipoprotein cholesterol (TG/HDL-C) by waist-to-height ratio (WHtR). Using weighted multivariable linear and logistic regression explored the relationships of CMI with glucose metabolism markers, IR, preDM, and DM. Nonlinear associations were assessed using generalized additive models (GAM), smooth curve fittings, and two-piecewise logistic regression., Results: Multivariate regression revealed positive correlations between CMI and glucose metabolic biomarkers, including FBG (β = 0.08, 95% CI: 0.06-0.10), HbA1c (β = 0.26, 95% CI: 0.22-0.31), FSI (β = 4.88, 95% CI: 4.23-5.54), and HOMA-IR (β = 1.85, 95% CI: 1.56-2.14). There were also significant correlations between CMI and increased risk of IR (OR = 3.51, 95% CI: 2.94-4.20), preDM (OR = 1.49, 95% CI: 1.29-1.71), and DM (OR = 2.22, 95% CI: 2.00-2.47). Inverse nonlinear L-shaped associations were found between CMI and IR, preDM, and DM, with saturation inflection points at 1.1, 1.45, and 1.6, respectively. Below these thresholds, increments in CMI significantly correlated with heightened risks of IR, preDM, and DM., Conclusions: CMI exhibited inverse L-shaped nonlinear relationships with IR, preDM, and DM, suggesting that reducing CMI to a certain level might significantly prevent these conditions., (© 2024. The Author(s).)

Introduction: Despite the widespread provision of free contraceptives and post-abortion care (PAC) services, China grapples with a high rate of unintended pregnancies and subsequent abortions. We aimed to study the evolving characteristics of women seeking abortion and their contraceptive practices before and after abortions, to shed light on the optimisation of Chinese PAC services., Methods: This study utilised data from an abortion cohort between 2019 and 2021. We studied their demographic features, contraception and abortion histories, reasons and choices using chi-square or linear-by-linear tests. We also explored the potential impact of receiving services at PAC facilities on post-abortion contraception use and repeat abortions using logistic regression models., Results: Among the 9005 participants, 43.4% experienced repeat abortion, without a discernible trend over the 3 years. Noteworthy increases were observed in the percentages of college students (from 1.7% to 6.6%, p<0.01) and middle-aged women (from 23.2% to 26.8%, p<0.01) seeking abortions. Surgical abortion was chosen by nearly 90% of participants with a continuously increasing trend ( p trend <0.01). Nearly half of the participants experienced unintended pregnancies due to non-use of contraception. Of the remainder, the majority preferred less or the least effective methods both before and after abortion. Women residing in moderate-gross domestic product (GDP) regions faced a higher risk of repeat abortions (OR 1.33, 95% CI 1.16 to 1.54). Despite this, high-quality PAC services may encourage the use of reliable contraceptive methods, with 86.8% of women changing from least effective or no methods to (most) effective methods post-abortion, and prevent repeat abortions (OR 0.65, 95% CI 0.56 to 0.75)., Conclusions: Increased proportions of college students and middle-aged multiparous women seeking abortions were observed, together with inappropriate preferences for less effective contraception and increasing choice of surgical abortions. Future research should extend the focus to cover the entire abortion period, advocate the rational selection of contraceptive methods, and emphasise the specified PAC services tailored to different socioeconomic groups., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Widely-used C 60 fullerene nanoparticles (C 60 ) result in their release into the aquatic environment, which may affect the distribution and toxicity of pollutants such as arsenic (As), to aquatic organism. In this study, arsenate (As(V)) accumulation, speciation and subcellular distribution was determined in Danio rerio (zebrafish) intestine, head and muscle tissues in the presence of C 60 . Meanwhile we compared how single-walled carbon nanotubes (SWCNTs), multi-walled carbon nanotubes (MWCNTs), graphene oxide (GO) and graphene (GN) nanoparticles alter the behaviors of As(V). Results showed that C 60 significantly inhibited As accumulation and toxicity in D. rerio, due to a decrease in total As and monomethylarsonic acid (MMA) and As(V) species concentrations, a lower relative distribution in the metal-sensitive fraction (MSF). It was attributed that C 60 may coat As(V) ion channels and consequently, affect the secretion of digestive enzymes in the gut, favoring As excretion and inhibiting As methylation. Similarly, MWCNTs reduced the species concentration of MMA and As(V) in the intestines, low GSH (glutathione) contents in the intestine. Due to the disparity of other carbon-based nanomaterial morphologies, SWCNTs, GO and GN exhibited the various effects on the toxicity of As(V). In addition, the possible pathway of arsenobetaine (AsB) biosynthesis included migration from the intestine to muscle in D. rerio, with the precursor of AsB likely to be 2-dimethylarsinylacetic acid (DMAA). The results of this study suggest that C 60 is beneficial for controlling As(V) pollution and reducing the impact of As(V) biogeochemical cycles throughout the ecosystem., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Intracellular trafficking, an extremely complex network, dynamically orchestrates nearly all cellular activities. A versatile method that enables the manipulation of target transport pathways with high spatiotemporal accuracy in vitro and in vivo is required to study how this network coordinates its functions. Here, a new method called RIVET (Rapid Immobilization of target Vesicles on Engaged Tracks) is presented. Utilizing inducible dimerization between target vesicles and selective cytoskeletons, RIVET can spatiotemporally halt numerous intracellular trafficking pathways within seconds in a reversible manner. Its highly specific perturbations allow for the real-time dissection of the dynamic relationships among different trafficking pathways. Moreover, RIVET is capable of inhibiting receptor-mediated endocytosis. This versatile system can be applied from the cellular level to whole organisms. RIVET opens up new avenues for studying intracellular trafficking under various physiological and pathological conditions and offers potential strategies for treating trafficking-related disorders., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Photodynamic therapy (PDT) is a clinically approved therapeutic modality that has shown great potential for cancer treatment. However, there exist two major problems hindering PDT applications: the nonspecific phototoxicity requiring patients to stay in dark post-PDT, and the limited photodynamic efficiency. Herein, we report a photo-triggered porphyrin polyelectrolyte nanoassembling (photo-triggered PPN) strategy, in which porphyrin photosensitizer and photoswitchable energy accepter are assembled into polyelectrolyte micelles by a combined force of charge interaction and metal-ligand coordination. The polyelectrolyte-based PPN exhibits good biocompatibility, and bestows a unique "confining isolated" inner microenvironment for fully overcoming the π-π stacking of porphyrins with significant photodynamic efficiency (123-fold enhancement). Due to the high Förster resonance energy transfer (FRET) (91.5%) between porphyrin and photoswitch in closed-form, we could use light as a specific trigger to modulate photoswitch between closed- and open-form, and manipulate the 1O2 generation in three stages: pre-PDT (quenching 1O2 generation), during PDT (activating 1O2 generation), and post-PDT (silencing 1O2 generation). This de novo strategy has for the first time realized remotely manipulating and boosting 1O2 generation in PDT, well resolving the critical and general challenges of limited photodynamic efficiency and side effects from nonspecific phototoxicity., (© 2024 Wiley‐VCH GmbH.)

Soil fungi are pivotal in alpine and arctic ecosystems that are vulnerable to climate changes. Previous studies have shown broad connections between soil fungi in the arctic and alpine regions, but most of these studies are mainly from Europe and North America, with more sporadic studies from East Asia. Currently, little is known about the biogeographic relationships between soil fungi in alpine meadows of southwestern China (AMSC) and other regions of the world. In addition, the regional-scale spatial patterns of fungal communities in the AMSC, as well as their driving factors and ecological processes, are also poorly understood. In this study, we collected roots and surrounding soils of two dominant ectomycorrhizal plants, Bistorta vivipara and B. macrophylla from the AMSC, and performed bioinformatic and statistical analyses based on high-throughput sequencing of ITS2 amplicons. We found that: (1) fungi from the AMSC were closely related with those from boreal forests and tundra, and saprotrophic fungi had higher dispersal potential than ectomycorrhizal fungi; (2) community compositions exhibited clear divergences among geographic regions and between root and soil samples; (3) climate was the predominant factor driving regional-scale spatial patterns but had less explanatory power for saprotrophic and total fungi from roots than those from soils; (4) homogeneous selection and drift were the key ecological processes governing community assembly, but in communities of saprotrophic and total fungi from soil samples, drift contributed less and its role was partially replaced by dispersal limitation. This study highlights the importance of climatic selection and stochastic processes on fungal community assembly in alpine regions, and emphasizes the significance of simultaneously investigating fungi with different trophic modes and from both roots and soils., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: There is conflicting evidence regarding whether heart failure (HF) increases the risk of developing cancer., Objective: This study aimed to assess the association between HF and incident cancer, considering gender differences and HF phenotypes., Methods: This retrospective study was conducted on data of adult individuals, free of cancer at baseline, from the First Affiliated Hospital of Wenzhou Medical University between January 2009 and February 2023. The patients with HF were categorized as HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). The primary outcome was incident cancer, including obesity-related, tobacco-related, lung, colorectal and breast cancers., Results: Of 33 033 individuals enrolled, 16 722 were diagnosed with HF, including 10 086 (60.3%) with HFpEF and 6636 (39.7%) with HFrEF. During a median follow-up period of 4.6 years (inter-quartile range: 2.6-7.3), incident cancer was diagnosed in 10.5% (1707 patients) of the non-HF group and 15.1% (2533 individuals) of the HF group. After adjusting for potential confounding factors, patients with HF had a 58% increased risk of cancer than those without HF [adjusted hazard ratio (HR) 1.58, 95% confidence interval (CI) 1.48-1.69, P < 0.001]. This risk was consistent across genders (female: adjusted HR 1.95, 95% CI 1.74-2.18, P < 0.001; male: adjusted HR 1.41, 95% CI 1.30-1.54, P < 0.001) and HF phenotypes (HFpEF: adjusted HR 1.69, 95% CI 1.57-1.81, P < 0.001; HFrEF: adjusted HR 1.32, 95% CI 1.20-1.46, P < 0.001)., Conclusions: Both HFpEF and HFrEF are associated with an increased risk of incident cancer. This correlation maintains its validity across genders., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Apical hypertrophic cardiomyopathy (ApHCM) is a variant of hypertrophic cardiomyopathy, with distinct clinical characteristics and outcomes. We aimed to clarify the natural history of patients with ApHCM and identify the risk of end-stage heart failure incidence., Methods and Results: This retrospective study was conducted on patients with hypertrophic cardiomyopathy in China between January 2009 and February 2024. Patients were stratified into ApHCM and non-ApHCM groups. The primary outcome was a composite of major adverse cardiovascular events, including all-cause deaths, heart failure hospitalization, sudden cardiac death, and ventricular tachycardia. The secondary outcome was the incidence of end-stage heart failure, defined as left ventricular ejection fraction <50%. Kaplan-Meier and univariable and multivariable Cox proportional analyses were applied. Adjustment variables were included for important baseline characteristics, comorbidities, and medication use. Of 5653 patients enrolled with hypertrophic cardiomyopathy, 584 (10.3%) had ApHCM and 5069 (89.7%) had non-ApHCM. During the median follow-up period of 4.6 years (1.6-8.0 years), major adverse cardiovascular events occurred in 32.2% (n=1808), with a lower incidence in patients with ApHCM than non-ApHCM (20.4% versus 33.3%, P <0.001). Non-ApHCM was an independent predictor of major adverse cardiovascular events (hazard ratio [HR], 1.65 [95% CI, 1.36-1.99]; P <0.001). In the serial cohort, patients with ApHCM exhibited a lower incidence of end-stage heart failure than those with non-ApHCM (12.4% versus 2.7%, P <0.001). Non-ApHCM was associated with a higher risk of end-stage heart failure development (HR, 2.31 [95% CI, 1.28-4.15]; P <0.001). In subgroup and sensitivity analysis, the results were consistent for our main and secondary outcomes., Conclusions: ApHCM is relatively common in hypertrophic cardiomyopathy and shows lower rates of all-cause mortality and heart failure hospitalizations than non-ApHCM.

This study evaluated the acceptability and tolerability of three alcohol-based hand rubs (ABHRs) at Sarawak General Hospital, Malaysia. Conducted from 12-26 November 2021 using a modified WHO Protocol, it involved a survey among health workers and concessionaires, with a 35% response rate (1,598 of 4,628 participants). The majority were nurses (60.8%), with the medical division most represented (28.4%). Most respondents (93.2%) used ABHRs at least five days a week and found them easily accessible (72.3%). Product B was the preferred ABHR (65%), primarily for its color and fragrance, surpassing WHO's 50% approval rate in these aspects. However, no other product features met WHO criteria. There were no significant differences in self-reported skin tolerability across the products, and none achieved overall WHO approval. These results offer important insights for ABHR selection in developing countries and highlight the value of the WHO Protocol in assessing product acceptability and tolerability.

Hypertensive renal damage (HRD) is a major cause of end-stage renal disease. Among the causes of end-stage renal disease, HRD accounts for nearly 34% of the total number of cases. Antihypertensive treatment is primarily drug-based, but therapeutic efficacy is less effective and can have serious side effects. Chinese medicine (CM) has significant advantages in the treatment of HRD. CM is rich in various active ingredients and has the property of targeting multiple targets and channels. Therefore, the regulatory network of CM on disease is complex. A large number of CM have been employed to treat HRD, either as single applications or as part of compound formulations. The key possible mechanisms of CM for HRD include regulation of the renin-angiotensin-aldosterone system, antioxidation, anti-inflammation, rescue of endothelial function, regulation of vasoactive substance secretion and obesity-related factors, etc. This review summarized and discussed the recent advance in the basic research mechanisms of CM interventions for HRD and pointed out the challenges and future prospects., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To report the efficiency of OT utilisation and perioperative outcomes with a dedicated spine team approach in AIS patients who underwent posterior spinal fusion (PSF) surgeries in a consecutive case operation list., Methods: Three AIS patients operated in a day (8:00 AM-8:00 PM) by a dedicated spine team were recruited between 2021 and 2022. The dedicated team comprised of three senior spine consultants who operated using a dual attending surgeon strategy, an anaesthetic consultant, dedicated surgical scrub nurses, anaesthesiology nurses, radiographers, and neuromonitoring technicians. Patients were categorised according to the sequence of operation list of the day (Case 1, Case 2, and Case 3). OT efficiency was represented by OT time in five stages (preoperative time, operative time, postoperative time, total OT time, and turnover time). OT time and perioperative outcomes were compared., Results: 102 cases were analysed. On average, Case 1 began at 8:38 AM whereas Case 3 ended by 5:54 PM. OT efficiency was consistent throughout the day of operation with comparable OT time in all five stages between groups (p > 0.05). The mean turnover time was 15.1 ± 13.5 min and the mean operative time was 123.0 ± 28.1 min. Intraoperative arterial blood gas (ABG) parameters were maintained in an optimal range. The complication rate was 2.0% (N = 2/102)., Conclusion: Consistent OT efficiency was demonstrated with a dedicated spine team approach. Despite performing three AIS cases in a consecutive case operation list, patients' safety was not compromised as perioperative outcomes between groups were comparable., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The diagnosis and treatment of attention deficit hyperactivity disorder (ADHD) comorbid with epilepsy have been insufficiently addressed in China. We conducted a study in China to investigate the current status, diagnosis, and treatment of ADHD in children to further our understanding of ADHD comorbid with epilepsy, strengthen its management, and improve patients' quality of life., Methods: We carried out a multicenter cross-sectional survey of children with epilepsy across China between March 2022 and August 2022. We screened all patients for ADHD and compared various demographic and clinical factors between children with and without ADHD, including gender, age, age at epilepsy onset, duration of epilepsy, seizure types, seizure frequency, presence of epileptiform discharges, and treatment status. Our objective was to explore any possible associations between these characteristics and the prevalence of ADHD., Results: Overall, 395 epilepsy patients aged 6-18 years were enrolled. The age at seizure onset and duration of epilepsy ranged from 0.1-18 to 0.5-15 years, respectively. Focal onset seizures were observed in 212 (53.6%) patients, while 293 (76.3%) patients had epileptiform interictal electroencephalogram (EEG) abnormalities. Among the 370 patients treated with anti-seizure medications, 200 (54.1%) had monotherapy. Although 189 (47.8%) patients had ADHD, only 31 received treatment for it, with the inattentive subtype being the most common. ADHD was more common in children undergoing polytherapy compared to those on monotherapy. Additionally, poor seizure control and the presence of epileptiform interictal EEG abnormalities may be associated with a higher prevalence of ADHD., Conclusions: While the prevalence of ADHD was higher in children with epilepsy than in normal children, the treatment rate was notably low. This highlights the need to give more importance to the diagnosis and treatment of ADHD in children with epilepsy., (© 2024. Children's Hospital, Zhejiang University School of Medicine.)

Unlike conventional rigid counterparts, soft and stretchable electronics forms crack- or defect-free conformal interfaces with biological tissues, enabling precise and reliable interventions in diagnosis and treatment of human diseases. Intrinsically soft and elastic materials, and device designs of innovative configurations and structures leads to the emergence of such features, particularly, the mechanical compliance provides seamless integration into continuous movements and deformations of dynamic organs such as the bladder and heart, without disrupting natural physiological functions. This review introduces the development of soft, implantable electronics tailored for dynamic organs, covering various materials, mechanical design strategies, and representative applications for the bladder and heart, and concludes with insights into future directions toward clinically relevant tools., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The widespread emergence of airborne diseases has transformed our lifestyle, and respirators have become an essential part of daily life. Nevertheless, finding respirators that fit well can be challenging due to the variety of human facial sizes and shapes, potentially compromising protection. In addition, the current respirators do not inform the user of the air quality in case of continuous long-term use. Here, we introduce a smart filtering facepiece respirator incorporating a humidity sensor and pressure sensory feedback for self-fit adjusting and maintaining an adequate fit. The humidity detection sensor uses laser-induced graphene, and the pressure sensor array based on the dielectric elastomeric sponge monitors the respirator contact on the user's face, providing real-time closed-loop feedback and the wearer's fitting status. Those membrane sensors show outstanding performance, such as a low humidity hysteresis of 0.131 % and a precise pressure detection limit of 0.23 ± 0.02 kPa. As a result of the self-fit adjusting mode, the overall fit factor is increased by 10 % on average compared to the commercial respirator. This significant improvement in fit factor, coupled with the innovative design, has the potential to develop next-generation facepiece respirators as essential personal protective equipment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Georgia Tech a pending US patent application., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Two in vivo experiments were conducted to evaluate the potential of Pharbitis nil seeds (PA) as an anti-methanogenic additive to ruminant feed. In experiment 1, six Hanwoo steers (459.0 ± 25.8 kg) were fed either a total mixed ration (TMR; 32-d period) or TMR supplemented with PA at 5% dry matter (DM) intake (TMR-PA; 45-d period) for two consecutive periods. Fecal and urine outputs were measured in an apparent digestibility trial in both periods. Methane (CH 4 ) yield and heat energy (HE) were measured using respiratory chambers equipped with gas analyzers. In experiment 2, five rumen cannulated Holstein steers (744 ± 35 kg) were fed the same TMR or TMR-PA diets for 40 days; rumen samples were collected at 0, 1.5, and 3 h after feeding on the last day of the feeding period. In experiment 1, although there were no differences ( p > 0.05) in nutrients or gross energy intake (GEI) between the groups, an increase ( p < 0.05) in the apparent digestibility of DM (9.1%) and neutral detergent fiber (22.9%) was observed in the TMR-PA fed Hanwoo steers. Pronounced decreases ( p < 0.05) in CH 4 (g/Kg DM; 17.1%) and urinary N excretion (% N intake; 7.6%) were observed in the TMR-PA group, leading to a 14.7% increase in metabolizable energy intake (% GEI). However, only a numerical increase ( p > 0.05) in retained energy was observed due to the increase in HE loss. In experiment 2, a drastic decrease ( p < 0.05) in rumen ammonia concentration (56.3%) associated with an increased ( p = 0.091) rumen short-chain fatty acid concentration 1.5 h after feeding were observed in TMR-PA fed Holstein steers. A 26.6% increase ( p < 0.05) in the propionate proportion during the treatment period clearly reflected a shift in the ruminal H 2 sink after 3 h of feeding. A 40% reduction ( p = 0.067) in the relative abundance of rumen protozoa Entodinium caudatum was also observed. It was concluded that PA could be a natural feed additive for CH 4 and N emission abatement., 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 Bharanidharan, Xaysana, Hong, Kim, Byun, Lee, Tomple, Kim and Ibidhi.)

Phages, the natural predators of bacteria, were discovered more than 100 years ago. However, increasing antimicrobial resistance rates have revitalized phage research. Methods that are more time-consuming and efficient than wet-laboratory experiments are needed to help screen phages quickly for therapeutic use. Traditional computational methods usually ignore the fact that phage-bacteria interactions are achieved by key genes and proteins. Methods for intraspecific prediction are rare since almost all existing methods consider only interactions at the species and genus levels. Moreover, most strains in existing databases contain only partial genome information because whole-genome information for species is difficult to obtain. Here, we propose a new approach for interaction prediction by constructing new features from key genes and proteins via the application of K-means sampling to select high-quality negative samples for prediction. Finally, we develop DeepPBI-KG, a corresponding prediction tool based on feature selection and a deep neural network. The results show that the average area under the curve for prediction reached 0.93 for each strain, and the overall AUC and area under the precision-recall curve reached 0.89 and 0.92, respectively, on the independent test set; these values are greater than those of other existing prediction tools. The forward and reverse validation results indicate that key genes and key proteins regulate and influence the interaction, which supports the reliability of the model. In addition, intraspecific prediction experiments based on Klebsiella pneumoniae data demonstrate the potential applicability of DeepPBI-KG for intraspecific prediction. In summary, the feature engineering and interaction prediction approaches proposed in this study can effectively improve the robustness and stability of interaction prediction, can achieve high generalizability, and may provide new directions and insights for rapid phage screening for therapy., (© The Author(s) 2024. Published by Oxford University Press.)

Background: In the realm of pediatric cerebral palsy (CP), visual motor challenges often overshadow a child's developmental journey. This study delves into the responsiveness and crucial benchmarks, specifically the minimal clinically important difference (MCID), of the Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery VMI) among children with varying motor severities., Method: Eighty-eight children with CP (50 males, 38 females; aged three to 12 years) with Gross Motor Function Classification System (GMFCS) levels I to III were recruited from the rehabilitation department of Chang Gung Memorial Hospital in Taiwan. Each participant received the Beery VMI tests at baseline and at one-year follow-up. The standardized response mean (SRM) was calculated to determine the responsiveness of Beery VMI, and a distribution-based approach was used to estimate MCID., Results: The Beery VMI exhibited remarkable responsiveness across GMFCS levels I to III (SRM = 0.98-2.36). MCIDs for Beery VMI varied across severities, with ranges of 2.93 to 4.41 (0.2 S.D.), 7.31 to 11.49 (0.5 S.D.), and 11.70 to 18.38 (0.8 S.D.). Notably, in the visual perception subset, MCIDs were 3.93 to 4.03 (0.2 S.D.), 9.83 to 10.07 (0.5 S.D.), and 15.73 to 16.11 (0.8 S.D.). In the supplemental motor coordination subtest, MCIDs spanned 1.67 to 4.87 (0.2 S.D.), 4.18 to 12.17 (0.5 S.D.), and 6.68 to 19.47 (0.8 S.D.)., Conclusions: Beery VMI demonstrates robust responsiveness in children with CP. Motor-severity-tailored MCIDs offer a guide for clinicians and researchers, hinting at treatment efficacy. Particularly, lower change scores in VMI and motor coordination subtests may signal effective interventions for moderate motor disability over mild cases., Competing Interests: Declaration of Competing Interest Chia-Ling Chen reports financial support was provided by Ministry of Science and Technology. Chia-Ling Chen reports financial support was provided by Chang Gung Medical Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Question: How many couples with at least one child under 3 years would like to have another one or more child(ren) in Eastern China and will an in-cash subsidy be conducive to couple's fertility intentions?, Summary Answer: In sum, only 15.1% of respondents had further fertility intentions (FFI) before learning about the subsidy, and the planned in-cash subsidy policy increased respondents' overall FFI by 8.5%., What Is Known Already: Fertility has been declining globally and has reached a new low in China. The reasons why the Chinese three-child policy was under-realized, and how couples will react to a planned monthly ¥1000 (€141.2) subsidy policy, are not fully understood., Study Design Size Duration: During January and February 2022, a cross-sectional online survey aiming to understand families' expenses of raising a child under 3 years old, and couples' FFI, was conducted. During the survey period, 272 510 respondents scanned the QR code. This study reports the findings pertaining to questions on respondents' sociodemographic characteristics, household factors, FFI, and changes in intention from negative to positive after learning about the planned in-cash subsidy. After exclusion, 144 893 eligible responses were included., Participants/materials Setting Methods: Respondents' FFI, the effect of a planned ¥1000/month*36 months' in-cash subsidy (€5083.2 in total) on people with a negative FFI before the subsidy, and potential reasons for persistent negative FFI after learning about the subsidy were collected through an anonymous online survey. Stepwise binary logistic regression models were used to select associated factors. The potential fertility rate change and government costs were estimated. A stratified analysis by current child number and sensitivity analysis were also conducted., Main Results and the Role of Chance: In sum, 15.7% (22 804/144 893) of respondents were male, 15.1% of respondents reported a positive FFI, and 10.0% (12 288/123 051) without an FFI at first changed their intention after learning about the planned in-cash subsidy policy. For those who still said 'no FFI', 46.5%, 20.6%, and 14.7% chose pressure on housing status, expenses on children's education, and lack of time or energy for caring for another child as their first reasons. FFI was strongest in participants receiving the most financial support from their parents, i.e. grandparents (OR = 1.73, 95% CI = 1.63-1.84 for the >¥100 000/year group), and weakest in those already having two children (OR = 0.23, 95% CI = 0.22-0.24). For those with no FFI before learning about the subsidy policy, respondents with the highest house loan/rent (>¥120 000/year, OR = 1.27, 95% CI = 1.18-1.36) were more likely to change their FFI from 'No' to 'Yes', and those with the highest household income (>¥300 000/year, OR = 0.65, 95% CI = 0.60-0.71) were least susceptible to the policy. In our study population, about 1843 more births every year and an additional 0.3 children per woman were projected under a conservative estimation. Annual estimated cost at the provincial scale would be ¥817.7 (€115.5) million, about 1.02‰ of the total General Public Budget Revenue in 2022. The findings were generally robust in the stratified analysis and sensitivity analysis., Limitations Reasons for Caution: Selection bias and information errors may exist in the online survey responses. The large sample size and detailed further analysis were used to minimize such biases., Wider Implications of the Findings: Fertility intentions in Eastern China are rather low. Policymakers should focus more on financial and childcare burdens for a better realization of the three-child policy, including housing, education and childcare services. An in-cash subsidy, which has never been used in China previously, shows promising potential for increasing FFI. However, the application of such policy should be in line with local conditions for better cost-effectiveness regarding fertility-boosting and fiscal sustainability for the government in the long run., Study Funding/competing Interests: This work was supported by the National Key Research and Development Plan of China (2019YFC0840702). The authors declare no conflict of interests., Trial Registration Number: N/A., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

To create a healthier indoor environment via sustainable technologies, there is a growing demand for constructing high-performance air filters from natural materials. Addressing this need, we have fabricated high-performance protein air filters with a tailored frame-channel structure via electrospinning. The innovative feature of the protein air filter is generated by adding a small amount of an organic salt, tetrabutylammonium chloride (TBAC), to modulate the denaturation of zein for tuning electrical charge distribution and hydrophilicity of the protein solutions. The results highlight that the optimized filter with 1.0 wt% TBAC exhibits a denser nanofiber assembly on the frame and a sparser arrangement on the channel. Functionally, the filter demonstrates ultralow pressure drop (ca. 9.04 Pa) that is only a third of that observed in unmodified formulation and commercial air filters, while it maintains high filtration efficiency in capturing PM 2.5 (99.42% ± 0.30%) and PM 0.3 (98.25 ± 0.39%). More importantly, the filter indicates multifunctional perspectives, e.g., high removal efficiency for formaldehyde (HCHO) and PM 2.5 under high airflow rates (up to 8 L/min) or after prolonged testing period (120 min). Our design of the frame-channel structure for the protein air filter marks a leap forward in developing biomass-based structural materials.

Ethnopharmacological Relevance: Bu-Zhong-Yi-Qi Decoction(BZYQD) is a traditional formula commonly used in China, known for its effects in tonifying Qi and raising Yang. It can relieve symptoms of cognitive impairment such as forgetfulness and lack of concentration caused by qi deficiency, which is common in aging and debilitating. However, much of the current research on BZYQD has been focused on its impact on the digestive system, leaving its molecular mechanisms in improving cognitive function largely unexplored., Aim of the Study: Cognitive decline in the aging central nervous system is intrinsically linked to oxidative damage. This study aims to investigate the therapeutic mechanism of BZYQD in treating mild cognitive impairment caused by qi deficiency, particularly through repair of mitochondrial oxidative damage., Materials and Methods: A rat model of mild cognitive impairment (MCI) was established by administering reserpine subcutaneously for two weeks, followed by a two-week treatment with BZYQD/GBE. In vitro experiments were conducted to assess the effects of BZYQD on neuronal cells using a H 2 O 2 -induced oxidative damage model in PC12 cells. The open field test and the Morris water maze test evaluated the cognitive and learning memory abilities of the rats. HE staining and TEM were employed to observe morphological changes in the hippocampus and its mitochondria. Mitochondrial activity, ATP levels, and cellular viability were measured using assay kits. Protein expression in the SIRT3/MnSOD/OGG1 pathway was analyzed in tissues and cells through western blotting. Levels of 8-OH-dG in mitochondria extracted from tissues and cells were quantified using ELISA. Mitochondrial morphology in PC12 cells was visualized using Mito Red, and mitochondrial membrane potential was assessed using the JC-1 kit., Results: BZYQD treatment significantly improved cognitive decline caused by reserpine in rats, as well as enhanced mitochondrial morphology and function in the hippocampus. Our findings indicate that BZYQD mitigates mtDNA oxidative damage in rats by modulating the SIRT3/MnSOD/OGG1 pathway. In PC12 cells, BZYQD reduced oxidative damage to mitochondria and mtDNA in H 2 O 2 -induced conditions and was associated with changes in the SIRT3/MnSOD/OGG1 pathway., Conclusion: BZYQD effectively counteracts reserpine-induced mild cognitive impairment and ameliorates mitochondrial oxidative stress damage through the SIRT3/MnSOD/OGG1 pathway., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Prolonged length of stay (LOS) increases the economic burden on patients, therefore, optimizing LOS is a critical clinical challenge for physicians. This study aims to examine the correlation between the postoperative LOS and surgery-related adverse events after bullectomy. We defined prolonged postoperative LOS after bullectomy and analyzed the preoperative risk factors linked to prolonged LOS., Methods: In this retrospective study, we analyzed patient data from thoracoscopic bullectomy performed at our hospital between January 2018 and December 2023. The receiver operating characteristic (ROC) curve was used to identify the optimal cut-off values defining prolonged LOS after bullectomy. It was then characterized as prolonged LOS. Patients were divided into prolonged and normal LOS groups based on their postoperative duration. Further, univariate and multivariate logistic regression analyses were performed to identify preoperative risk factors associated with prolonged postoperative LOS after bullectomy., Results: Among the 152 patients analyzed, binary logistic regression revealed a significant effect of surgery-related adverse events after bullectomy on the LOS (P < 0.001). A postoperative LOS exceeding 3 days was considered prolonged. Among the 152 patients, 38.2 % (58/152) experienced a prolonged LOS out of which 20.4 % (31/152) developed surgery-related adverse events. Multivariate regression analysis revealed that preoperative risk factors associated with prolonged LOS included age ≥60 years (OR = 3.052, 95%CI 1.226-7.586, P = 0.016), current smoking status (OR = 2.754, 95%CI 1.482-6.346, P = 0.025), and ASA grade 3 (OR = 4.783, 95%CI 2.356-9.131, P = 0.003)., Conclusion: In summary, the postoperative length of stay beyond 3 days after bullectomy was considered prolonged. The preoperative risk factors associated with prolonged postoperative stays after bullectomy included age (over 60), current smoking, and grade 3 ASA. Therefore, quick identification and intervention in patients with these high-risk factors may promote rapid recovery., 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/Objectives: This study aims to compare the health-related quality of life (HRQOL) between healthcare providers without chronic diseases and participants with chronic diseases presenting with one of the four different primary diagnoses on the health-related quality of life with six domains (HRQ-6D) scale. Methods: This is a cross-sectional study to compare the HRQOL between healthcare providers without chronic diseases and participants with chronic diseases. Data collection was performed from May 2022 to May 2023. Data for the comparison group were taken from healthcare providers without chronic diseases, and for the participant group with chronic diseases, the data were collected from actual patients with one of four types of primary diagnoses who were recruited from specialist cardiology, oncology, psychiatry, and nephrology clinics. All the participants of this study filled in the HRQ-6D. Results: There were 238 (58.6%) healthcare providers without chronic diseases who participated in this study, as well as 41 (10.1%) patients with end-stage renal disease (ESRD), 48 (11.8%) patients with cancer, and 40 (9.9%) patients who were depressed, and the remaining patients had heart disease. The means (SD) of HRQ-6D scores among healthcare providers without chronic diseases for pain, physical strength, emotion, mobility, self-care, perception of future health, and overall HRQ-6D score were 75.3% (19.8), 74.5% (21.1), 85.6% (18.4%), 93.0% (12.3), 91.6% (13.9), 74.2% (23.3), and 82.4% (13.6), respectively. In comparisons between healthcare providers without chronic diseases and participants with chronic diseases, all mean differences of the overall HRQ-6D score and its domains and dimensions were statistically significant ( p < 0.001). Conclusions: The overall score of the HRQ-6D, as well as its domains and dimensions are sensitive in detecting the study participants with chronic diseases from among those without chronic diseases. Therefore, the HRQ-6D is a reliable and valid scale to measure HRQOL. Future studies may use this scale for interventional, observational, and cost-effectiveness studies.

Identification of potential bacterial players in colorectal tumorigenesis has been a focus of intense research. Herein, we find that Clostridium symbiosum (C. symbiosum) is selectively enriched in tumor tissues of patients with colorectal cancer (CRC) and associated with higher colorectal adenoma recurrence after endoscopic polypectomy. The tumorigenic effect of C. symbiosum is observed in multiple murine models. Single-cell transcriptome profiling along with functional assays demonstrates that C. symbiosum promotes the proliferation of colonic stem cells and enhances cancer stemness. Mechanistically, C. symbiosum intensifies cellular cholesterol synthesis by producing branched-chain amino acids (BCAAs), which sequentially activates Sonic hedgehog signaling. Low dietary BCAA intake or blockade of cholesterol synthesis by statins could partially abrogate the C. symbiosum-induced cell proliferation in vivo and in vitro. Collectively, we reveal C. symbiosum as a bacterial driver of colorectal tumorigenesis, thus identifying a potential target in CRC prediction, prevention, and treatment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

cAMP response element binding (CREB) protein 2 (CRTC2) is a transcriptional coactivator of CREB and plays an important role in the immune system. Thus far, the physiological roles of Crtc2 in teleost are still poorly understood. In this study, the crtc2 gene was identified and characterized from yellow catfish (Pelteobagrus fulvidraco; therefore, the gene is termed as pfcrtc2), and its evolutionary and molecular characteristics as well as potential immunity-related roles were investigated. Our results showed that the open reading frame of pfcrtc2 was 2346 bp in length, encoding a protein with 781 amino acids. Gene structure analysis revealed its existence of 14 exons and 13 introns. A phylogenetic analysis proved that the tree of crtc2 was clustered into five groups, exhibiting a similar evolutionary topology with species evolution. Multiple protein sequences alignment demonstrated high conservation of the crtc2 in various vertebrates with similar structure. Syntenic and gene structural comparisons further established that crtc2 was highly conserved, implying its similar roles in diverse vertebrates. Tissue distribution pattern detected by quantitative real-time PCR showed that the pfcrtc2 gene was almost expressed in all detected tissues except for eyes, with the highest expression levels in the gonad, indicating that Crtc2 may play important roles in various tissues. In addition, pfcrtc2 was transcribed at all developmental stages in yellow catfish, showing the highest expression levels at 12 h after fertilization. Finally, the transcriptional profiles of crtc2 were significantly increased in yellow catfishes injected with Aeromonas hydrophila or Poly I:C, which shared a consistent change pattern with four immune-related genes including IL-17A, IL-10, MAPKp38, and NF-κBp65, suggesting pfCrtc2 may play critical roles in preventing both exogenous bacteria and virus invasion. In summary, our findings lay a solid foundation for further studies on the functions of pfcrtc2, and provide novel genetic loci for developing new strategies to control disease outbreak in teleost., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

As the regenerative mechanisms of biological organisms, self-healing provides useful functions for soft electronics or associated systems. However, there have been few examples of soft electronics where all components have self-healing properties while also ensuring compatibility between components to achieve multifunctional and resilient bio-integrated electronics. Here, we introduce a stretchable, biodegradable, self-healing conductor constructed by combination of two layers: (i) synthetic self-healing elastomer and (ii) self-healing conductive composite with additives. Abundant dynamic disulfide and hydrogen bonds of the elastomer and conductive composite enable rapid and complete recovery of electrical conductivity (~1000 siemens per centimeter) and stretchability (~500%) in response to repetitive damages, and chemical interactions of interpenetrated polymer chains of these components facilitate robust adhesion strength, even under extreme mechanical stress. System-level demonstration of soft, self-healing electronics with diagnostic/therapeutic functions for the urinary bladder validates the possibility for versatile, practical uses in biomedical research areas.

Background: Surgical resection is the primary treatment for gastrointestinal (GI) cancers, but postoperative skeletal muscle loss (SML) is common and linked to poor prognosis. This study aims to identify patterns of muscle change, examine its association with quality of life (QoL), and explore predictors of SML in the first 3 months., Patients and Methods: A prospective cohort study was conducted on patients newly diagnosed with GI cancer and undergoing surgery in China between September 2021 and May 2022. Skeletal muscle mass (SMM) and QoL were assessed at admission, 7 days, 1 month, and 3 months post-surgery. Demographic, clinical data, and biomarkers were collected. Missing data were imputed using multiple imputation. Data were analyzed using growth mixture modelling, bivariate analyses, and logistic regression., Results: A total of 483 patients completed baseline assessment. Of the 242 patients with complete muscle assessments, 92% experienced SML. Three distinct patterns of muscle change were identified: 57% had normal preoperative SMM with mild postoperative SML, 16% had low preoperative SMM with moderate SML, and 27% had normal preoperative mass but severe postoperative SML. Moderate/severe SML was associated with more postoperative complications, poorer health, and higher symptom burden. Independent predictors included advanced age, preoperative sarcopenia, advanced cancer stage, and low prognostic nutrition index (PNI ≤ 45). The results did not change when using imputed values., Conclusions: Although SML is prevalent, patterns of muscle change are heterogeneous among patients. Advanced age, preoperative sarcopenia, advanced cancer stage, and cancer-related inflammation are predictors for moderate/severe SML, highlighting the need for early detection and management., (© 2024. Crown.)

Dysphagia is more common in conditions such as stroke, Parkinson's disease, and head and neck cancer. This can lead to pneumonia, choking, malnutrition, and dehydration. Currently, the diagnostic gold standard uses radiologic imaging, the videofluoroscopic swallow study (VFSS); however, it is expensive and necessitates specialized facilities and trained personnel. Although several devices attempt to address the limitations, none offer the clinical-grade quality and accuracy of the VFSS. Here, this study reports a wireless multimodal wearable system with machine learning for automatic, accurate clinical assessment of swallowing behavior and diagnosis of silent aspirations from dysphagia patients. The device includes a kirigami-structured electrode that suppresses changes in skin contact impedance caused by movements and a microphone with a gel layer that effectively blocks external noise for measuring high-quality electromyograms and swallowing sounds. The deep learning algorithm offers the classification of swallowing patterns while diagnosing silent aspirations, with an accuracy of 89.47%. The demonstration with post-stroke patients captures the system's significance in measuring multiple physiological signals in real-time for detecting swallowing disorders, validated by comparing them with the VFSS. The multimodal electronics can ensure a promising future for dysphagia healthcare and rehabilitation therapy, providing an accurate, non-invasive alternative for monitoring swallowing and aspiration events., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The relationship among polycystic ovary syndrome (PCOS), endometrial cancer (EC), and glycometabolism remains unclear. We explored shared genes between PCOS and EC, using bioinformatics to unveil their pathogenic connection and influence on EC prognosis. Gene Expression Omnibus datasets GSE226146 (PCOS) and GSE196033 (EC) were used. A protein-protein interaction (PPI) network was constructed to identify the central genes. Candidate markers were screened using dataset GSE54250. Differences in marker expression were confirmed in mouse PCOS and human EC tissues using RT-PCR and immunohistochemistry. The effect of PGD on EC proliferation and migration was explored using Ki-67 and Transwell assays. PGD's impact on the glycometabolic pathway within carbon metabolism was assessed by quantifying glucose content and lactic acid production. R software identified 31 common genes in GSE226146 and GSE196033. Gene Ontology functional classification revealed enrichment in the "purine nucleoside triphosphate metabolism process," with key Kyoto Encyclopedia of Genes and Genomes pathways related to "carbon metabolism." The PPI network identified 15 hub genes. HK2, NDUFS8, PHGDH, PGD, and SMAD3 were confirmed as candidate markers. The RT-PCR analysis validated distinct HK2 and PGD expression patterns in mouse PCOS ovarian tissue and human EC tissue, as well as in normal and EC cells. Transfection experiments with Ishikawa cells further confirmed PGD's influence on cell proliferation and migration. Suppression of PGD expression impeded glycometabolism within the carbon metabolism of EC cells, suggesting PGD as a significant PCOS risk factor impacting EC proliferation and migration through modulation of single carbon metabolism. These findings highlight PGD's pivotal role in EC onset and prognosis., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Purpose: Vibrio vulnificus (V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs., Methods: An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis., Results: In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival (p = 0.014), reduced the serum creatinine (p = 0.002), urea nitrogen (p = 0.030), aspartate aminotransferase (p = 0.029), and alanine aminotransferase (p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1β: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1β, IL-6, TNF-α in liver (IL-1β: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1β: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid (p = 0.225), liver (p = 0.186), or kidney (p = 0.637)., Conclusion: Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus., (Copyright © 2024 Chinese Medical Association. Production and hosting by Elsevier B.V. All rights reserved.)

Athletes are at high risk of dehydration, fatigue, and cardiac disorders due to extreme performance in often harsh environments. Despite advancements in sports training protocols, there is an urgent need for a non-invasive system capable of comprehensive health monitoring. Although a few existing wearables measure athlete's performance, they are limited by a single function, rigidity, bulkiness, and required straps and adhesives. Here, an all-in-one, multi-sensor integrated wearable system utilizing a set of nanomembrane soft sensors and electronics, enabling wireless, real-time, continuous monitoring of saliva osmolality, skin temperature, and heart functions is introduced. This system, using a soft patch and a sensor-integrated mouthguard, provides comprehensive monitoring of an athlete's hydration and physiological stress levels. A validation study in detecting real-time physiological levels shows the device's performance in capturing moments (400-500 s) of synchronized acute elevation in dehydration (350%) and physiological strain (175%) during field training sessions. Demonstration with a few human subjects highlights the system's capability to detect early signs of health abnormality, thus improving the healthcare of sports athletes., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Purpose: To develop diagnostic recommendations for diffuse large B-cell vitreoretinal lymphoma (VRL) in Chinese patients., Methods: Retrospective observational case series. Seventy-three eyes of 40 VRL patients and 8 control patients were analyzed. Eighteen patients from Beijing Tongren Hospital and 46 patients from literature were involved as validations., Results: Diagnostic methods included (1) typical clinical manifestations; (2) vitreous cytology; (3) immunohistochemical examination of vitreous or choroid/retina; (4) aqueous humor or vitreous cytokine; (5) vitreous cell gene rearrangement; (6) vitreous flow cytometry. If patients meet (1)+(2)+(3), or if they meet (1), and two of (4), (5), (6) are positive, they can be diagnosed as VRL. The sensitivity and specificity values for accurate diagnosis were 0.975 and 1.00. One hundred percent eyes from Beijing Tongren Hospital and 92.7% eyes from literature can be diagnosed., Conclusion: We developed diagnostic recommendations for diffuse large B-cell VRL through vitreous cytology combined with multiple auxiliary examinations.

A new microsporidian disease of the pond-reared ridgetail white prawn, Palaemon carinicauda, was found in China. Light microscopy, pathology, and scanning electron microscopy showed that the parasite infected the host's skeletal muscle tissue and formed spherical sporophorous vesicles (SPOVs). Electron microscopy revealed that its merogonic life stages developed in direct contact with the host cytoplasm. The sporogonic life stages underwent octosporoblastic sporogony with the formation of eight uninucleate spores in each SPOV. Fresh SPOVs were 5.4 ± 0.55 µm in diameter. The octospores were oval and measured 2.3 × 1.5 μm (fresh) and 1.96 × 1.17 μm (fixed). The isofilar polar filament was coiled with 9-10 turns and arranged in two rows. Phylogenetic analysis based on the SSU rRNA gene suggests that this microsporidium has close affinities with members of the genera Potaspora and Apotaspora, but represents an independent generic taxon. We therefore propose the establishment of a new genus and species (Paospora carinifang n. gen., n. sp.) within the family Spragueidae. We also propose a taxonomic revision to transfer Potaspora macrobrachium to this new genus and reclassify it as Paospora macrobrachium comb. nov., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: As hypertensive heart disease (HHD) presents a significant public health challenge globally, we analysed its global, regional, and national burdens and trends from 1990 to 2019., Methods: We used data from the Global Burden of Disease (GBD) 2019 study, focussing on the age-standardised prevalence rates (ASPRs) of HHD prevalence, age-standardised disability-adjusted life year (DALY) rates, average annual percentage change (AAPC), and risk factor attributions. We compared the HHD burden across sociodemographic index (SDI) strata, gender, age groups, and 204 countries and territories., Results: In 2019, the global prevalence of HHD was estimated at 18 598 thousand cases, with DALYs reaching 21 508 thousand. From 1990 to 2019, the ASPRs increased (AAPC = 0.21; 95% confidence interval (CI) = 0.17, 0.24), while the age-standardised DALY rates decreased (AAPC = -0.45; 95% CI = -1.23, -0.93). We observed the highest increase in ASPRs in high-middle SDI quantile countries, and an overall negative correlation between age-standardised DALY rates and SDI. Individuals above 70 years of age were the most affected, particularly elderly women. There has been a significant increase in HHD burden attributed to high body mass index (BMI) since 1990. The burden of HHD is concentrated in the middle SDI quintile, with population ageing and growth being major drivers for the increase in DALYs. We identified opportunities for reducing age-standardised DALY rates in the middle SDI quintile or lower., Conclusion: Despite a declining trend in the age-standardised DALY rates, the ASPRs of HHD continue to rise, especially in high-middle SDI regions. Meanwhile, countries in middle and lower SDI quintiles face a higher burden of age-standardised DALY rates. Targeted attention towards elderly women and controlling high BMI, alongside enhancing hypertension and HHD management awareness, is crucial for reducing the global burden of HHD., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

The pancreatic tumor microenvironment presents multiple obstacles for polymer-based drug delivery systems, limiting tumor penetration and treatment efficacy. Here, we engineer a hyaluronidase/reactive oxygen species cascade-responsive size/charge bidirectional-tunable nanodelivery (btND, G/R@TKP/HA) for co-delivery of gemcitabine and KRAS siRNA, capable of navigating through tumor barriers and augmenting anticancer efficiency. When penetrating the tumor stroma barrier, the hyaluronic acid shell of the nanodelivery undergoes degradation by hyaluronidase in an extracellular matrix, triggering size tuning from large to small and charge tuning from negative to positive, thereby facilitating deeper penetration and cellular internalization. After endocytosis, the nanodelivery protonizes in the endo/lysosome, prompting rapid endo/lysosomal escape, effectively overcoming the lysosome barrier. Intracellular ROS further disrupt the nanodelivery, inducing its size tuning again from small to large and a positive charge decrease for high tumor retention and controlled drug release. The btND shows remarkable antitumor activity in pancreatic cancer mouse models, highlighting the efficacy of this approach in penetrating tumor barriers and enhancing anticancer outcomes., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Background: In recent years, there have been many instances of negative sentiments expressed by and resignations observed from doctors working in the Ministry of Health (MOH), Malaysia. However, little is known about the perspectives of medical students and their career intentions. This study aims to determine the current Malaysian medical students' career intentions immediately after graduation and upon completing the 2 years of housemanship and to establish the factors influencing these intentions., Methods: This was a cross-sectional study of 859 Malaysian medical students from 21 medical schools who voluntarily completed a self-administered online questionnaire that was disseminated by representatives from medical schools nationwide and social media platforms of a national medical student society., Results: 37.8% of the respondents were optimistic about a career with the Ministry of Health (MOH), Malaysia in the future. Most of the respondents (91.2%) plan to join and complete the MOH Housemanship programme as soon as possible after graduation, with the majority of them (66.2%) planning to complete it in their state of origin. After 2 years of Housemanship programme, only more than half of the respondents (63.1%) plan to continue their careers in MOH. Slightly more than a quarter (27.1%) of the total respondents plan to emigrate to practise medicine, with 80.7% of them planning to return to Malaysia to practise medicine after some years or after completing specialisation training. Combining the career intentions of Malaysian medical students immediately after graduation and upon completion of the 2 years housemanship programme, only a slight majority (57.5%) of the respondents plan to continue their career in MOH eventually. Most of the respondents (85.0%) intend to specialise., Conclusion: A concerning number of Malaysian medical students plan to leave the Ministry of Health workforce, the main healthcare provider in Malaysia, in the future. Urgent government interventions are needed to address the underlying factors contributing to the potential exodus of future doctors to prevent further straining of the already overburdened healthcare system, posing a significant threat to public well-being. An annual national study to track medical students' career intentions is recommended to gather crucial data for the human resources for health planning in Malaysia., (© 2024. The Author(s).)

Background: Intracranial hemorrhage is the major safety concern of standard-dose ticagrelor (90 mg twice daily) based dual antiplatelet therapy (DAPT). The bleeding avoidance strategy through dose de-escalation has been investigated in interventional cardiology. However, the preserved antithrombotic efficacy and better safety of half-dose (45 mg twice daily) ticagrelor remains unverified in patients undergoing stent-assist coiling (SAC) or flow diversion (FD) treating unruptured intracranial aneurysms (UIA)., Methods: A single-center, prospective, cohort study was conducted to compare DAPT with aspirin 100 mg daily plus half-dose ticagrelor vs standard-dose clopidogrel (75 mg daily) in UIA patients. The adenosine diphosphate inhibition (ADPi) rate was utilized to quantify the antagonization of adenosine diphosphate (ADP)-induced platelet aggregation. The patients were followed-up at 6 month after discharge. The primary efficacy outcome was the major adverse cardiovascular and cerebrovascular events (MACCE), and the primary safety outcome was major bleeding. The secondary outcome was minor hemorrhage., Results: Our study included 322 UIA patients, of which 254 patients were eventually enrolled after propensity score matching. The ADPi of half-dose ticagrelor (51.56%±31.46%) was comparable (P=0.089) to that of clopidogrel (57.44%±22.76%). The outcomes were also comparable. Five (3.94%) patients in the ticagrelor group and eight (6.30%) patients in the clopidogrel group reported MACCE (P=0.393). One patient in the ticagrelor group was diagnosed with asymptomatic intracranial hemorrhage 1 month after stenting. There were 36 (28.35%) minor hemorrhagic events in the ticagrelor group and 35 (27.56%) in the clopidogrel group, (P=0.889)., Conclusion: Half-dose ticagrelor was effective and safe as a potential alternative to clopidogrel in the DAPT regimen for patients undergoing SAC/FD for UIA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Protein kinase A (PKA) plays essential roles in diverse cellular functions. However, the spatiotemporal dynamics of endogenous PKA upon activation remain debated. The classical model predicts that PKA catalytic subunits dissociate from regulatory subunits in the presence of cAMP, whereas a second model proposes that catalytic subunits remain associated with regulatory subunits following physiological activation. Here we report that different PKA subtypes, as defined by the regulatory subunit, exhibit distinct subcellular localization at rest in CA1 neurons of cultured hippocampal slices. Nevertheless, when all tested PKA subtypes are activated by norepinephrine, presumably via the β-adrenergic receptor, catalytic subunits translocate to dendritic spines but regulatory subunits remain unmoved. These differential spatial dynamics between the subunits indicate that at least a significant fraction of PKA dissociates. Furthermore, PKA-dependent regulation of synaptic plasticity and transmission can be supported only by wildtype, dissociable PKA, but not by inseparable PKA. These results indicate that endogenous PKA regulatory and catalytic subunits dissociate to achieve PKA function in neurons., Competing Interests: Competing interests The authors declare no competing interests.

New therapeutics are necessary for preventing Plasmodium vivax malaria due to easy transmissibility and dormancy in the liver that increases the clinical burden due to recurrent relapse. We isolated 12 Pv Apical Membrane Antigen 1 (PvAMA1) specific human monoclonal antibodies from Peripheral Blood Mononuclear Cells of a Pv exposed individual. PvAMA1 is essential for sporozoite and merozoite invasion, making it a unique therapeutic target. HumAb 826827 blocked the invasion of human erythrocytes using Pv clinical isolates and inhibited sporozoite invasion of human hepatocytes in vitro (IC50 of 0.3 to 3.7 ug/mL). It also significantly reduced liver infection of chimeric FRG humHep mice in vivo. The crystal structure of rPvAMA1 bound to 826827 shows that 826827 partially occupies the highly conserved hydrophobic groove in PvAMA1 that binds its known receptor, RON2. We have isolated a potent humAb that is isolate transcendent, blocks both pre erythrocytic and blood stage infection, and could be a new therapy for Pv.

Objective: To explore the diagnostic value of nanopore sequencing technology for detecting nontuberculous mycobacterial pulmonary disease (NTM-PD) in bronchial alveolar lavage fluid (BALF)., Methods: A retrospective analysis was conducted on 83 patients with suspected NTM-PD admitted to Anhui Chest Hospital from January 2021 to November 2023. All patients underwent bronchoscopic examination, and BALF samples were collected for smear acid-fast staining, mycobacterial culture, and nanopore sequencing. The diagnostic efficiencies of these three methods were compared., Results: Among these patients, 27 were diagnosed with NTM-PD, 43 with pulmonary tuberculosis (PTB), and 13 with other lung diseases (OLD). The sensitivity, specificity, positive and negative predictive value of nanopore sequencing for diagnosing NTM-PD were 88.9%, 87.5%, 77.4%, and 94.2%, respectively. Nanopore sequencing demonstrated significantly higher sensitivity than smear and culture methods. The area under the receiver operating characteristic (ROC) curve (AUC) for nanopore sequencing was 0.882, significantly higher than that of smear (0.547) and culture (0.658), with P values less than 0.05., Conclusion: Nanopore sequencing technology has high diagnostic efficiency for NTM-PD and can directly identify bacterial species, but specificity issues should be considered in clinical application., Competing Interests: None., (AJTR Copyright © 2024.)

6-methoxybenzoxazolinone (6-MBOA) is a secondary plant metabolite predominantly found in monocotyledonous plants, especially Gramineae. In damaged tissue, 2-β-D-glucopyranosyloxy-4-hydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA-Glc) is hydrolyzed to DIMBOA, which spontaneously decomposes into 6-MBOA. It is commonly detected in plants consumed by voles and livestock and can also be present in cereal-based products. Discovered in 1955, this compound is renowned for its ability to trigger animal reproduction. However, there is a lack of research on its functional and mechanistic properties, leaving much of their potential unexplored. This review aimed to comprehensively summarize the effects of 6-MBOA on animal reproduction and human health, as well as its defensive role against herbivores. Studies have shown that 6-MBOA effectively inhibits the digestion, development, growth, and reproduction of insects. 6-MBOA may act as a partial agonist of melatonin and exert a regulatory role in mammalian reproduction, resulting in either promoting or inhibiting effects. 6-MBOA has been theorized to possess anti-tumor, anti-AIDS, anti-anxiety, and weight-loss effects in humans. However, insufficient attention has been paid to its defense properties against mammalian herbivores, and the mechanisms underlying its effects on mammalian reproduction remain unclear. In addition, research on its impact on human health is still in its preliminary stages. The review emphasizes the need for further systematic and comprehensive research on 6-MBOA to fully understand its diverse functions. Elucidating the effects of 6-MBOA on animal reproduction, adaptation, and human health would advance our understanding of plant-herbivore coevolution and the influence of environmental factors on animal population dynamics. Furthermore, this knowledge could potentially promote its application in human health and animal husbandry., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The synthesis of polycyclic aromatic hydrocarbon (PAH) data allows us to quantify and gain insights into the spatiotemporal dynamics of PAH contamination in marine bays. Here, a data synthesis framework was developed to understand data-driven insights into the spatiotemporal levels, compositional profiles, and potential sources of PAHs in water and sediment of marine bays. PAHs were detected in 69 bays worldwide, with contamination hotspots located in Asian bays. PAH concentrations in pre-2000 were significantly lower than those in the 2000s and post-2010, while the dominant species in water and sediment were 2-3 ring and 4-6 ring PAHs, respectively. The composition patterns of PAHs included 2-3 ring, 3-5 ring, and 4-5 ring dominant categories, but no significant distance decay relationship was found in the composition similarity due to international energy trade. Temporal dynamic patterns of concentrations included Descending-, Ascending-, and Inverted V-type, whereas over longer time spans, the pattern is more similar to the Inverted V-type owing to the reductions in emission intensity. PAHs were derived from both petrogenic and pyrolytic sources, with combustion from both coal and petroleum being the dominant source. These data-driven discoveries provide quantitative insights into the spatiotemporal patterns in the concentration and composition of PAHs, contributing to the mitigation of PAH contamination.

There is insufficient data on systemic embolic events (SSEs) in patients with ischemic left ventricular aneurysm (LVA) concerning the impact of anticoagulation therapy. In this retrospective cohort study with 1043 patients with ischemic LVA, SSEs occurred in 7.2% over 2.4 years. After adjusting for relevant factors, the use of anticoagulants was independently associated with a lower incidence of SSE (3.1% vs. 9.0%, P < 0.001; subdistribution hazard ratios (SHR) 0.21, 95% confidence intervals (CI) 0.10-0.44, P < 0.001), with no significant difference in net adverse clinical events (NACEs) (10.6% vs. 13.3%, P = 0.225). Specifically, anticoagulation in patients with apical segment akinesis significantly reduced SSEs (3.9% vs. 13.6%, P = 0.002) and NACE rates (7.8% vs. 19.4%, P = 0.002). Major bleeding rates did not significantly differ between groups (5.6% vs. 3.5%, P = 0.111). These findings highlight the SSE risk in ischemic LVA and suggest potential benefits of anticoagulation, particularly in those with apical segment akinesis. These findings need to be validated in independent datasets., (© 2024. The Author(s).)

Preclinical studies are crucial for developing amyotrophic lateral sclerosis drugs. Current FDA-approved drugs have been created by monitoring limb muscle function and histological analysis of amyotrophic lateral sclerosis model animals. Drug candidates for this disease have yet to be tested for bulbar-onset type due to the limitations of traditional preclinical tools: excessive animal use and discrete detection of disease progress. Here, our study introduces an all-in-one, wireless, integrated wearable system for facilitating continuous drug efficacy assessment of dysphagia-related muscles in animals during natural eating behaviors. By incorporating a kirigami-based strain-isolation mechanism, this device mounted on the skin of animals mitigates electromyography signal contamination caused by unpredictable animal movements. Our findings indicate this system, measuring the progression of motor neuron denervation, offers high precision in monitoring drug effects on dysphagia-responsible bulbar muscles. This study paves the way for more humane and efficient approaches to developing treatment solutions for degenerative neuromuscular diseases., (© 2024. The Author(s).)