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The ability to detect environmental cold serves as an important survival tool. The sodium channels NaV1.8 and NaV1.9, as well as the TRP channel Trpm8, have been shown to contribute to cold sensation in mice. Surprisingly, transcriptional profiling shows that NaV1.8/NaV1.9 and Trpm8 are expressed in nonoverlapping neuronal populations. Here we have used in vivo GCaMP3 imaging to identify cold-sensing populations of sensory neurons in live mice. We find that ~80% of neurons responsive to cold down to 1 °C do not express NaV1.8, and that the genetic deletion of NaV1.8 does not affect the relative number, distribution, or maximal response of cold-sensitive neurons. Furthermore, the deletion of NaV1.8 had no observable effect on transient cold-induced (≥5 °C) behaviors in mice, as measured by the cold-plantar, cold-plate (5 and 10 °C), or acetone tests. In contrast, nocifensive-like behavior to extreme cold-plate stimulation (-5 °C) was completely absent in mice lacking NaV1.8. Fluorescence-activated cell sorting (FACS) and subsequent microarray analysis of sensory neurons activated at 4 °C identified an enriched repertoire of ion channels, which include the Trp channel Trpm8 and potassium channel Kcnk9, that are potentially required for cold sensing above freezing temperatures in mouse DRG neurons. These data demonstrate the complexity of cold-sensing mechanisms in mouse sensory neurons, revealing a principal role for NaV1.8-negative neurons in sensing both innocuous and acute noxious cooling down to 1 °C, while NaV1.8-positive neurons are likely responsible for the transduction of prolonged extreme cold temperatures, where tissue damage causes pan-nociceptor activation. [ABSTRACT FROM AUTHOR]

Background: Opioid-induced hyperalgesia is recognized in the laboratory and the clinic, generating central hyperexcitability in the absence of peripheral pathology. We investigated pregabalin, indicated for neuropathic pain, and ondansetron, a drug that disrupts descending serotonergic processing in the central nervous system, on spinal neuronal hyperexcitability and visceral hypersensitivity in a rat model of opioid-induced hyperalgesia.Methods: Male Sprague-Dawley rats (180-200 g) were implanted with osmotic mini-pumps filled with morphine (90 μg · μl⁻¹ · h⁻¹) or saline (0.9% w/v). On days 7-10 in isoflurane anesthetized animals, we evaluated the effects of (1) systemic pregabalin on spinal neuronal and visceromotor responses, and (2) spinal ondansetron on dorsal horn neuronal response. Messenger ribonucleic acid concentrations of α2δ-1, 5HT3A, and μ-opioid receptor in the dorsal root ganglia of all animals were analyzed.Results: In morphine-treated animals, evoked spinal neuronal responses were enhanced to a subset of thermal and mechanical stimuli. This activity was attenuated by pregabalin (by at least 71%) and ondansetron (37%); the visceromotor response to a subset of colorectal distension pressures was attenuated by pregabalin (52.8%; n = 8 for all measures, P < 0.05). Messenger ribonucleic acid concentrations were unchanged.Conclusions: The inhibitory action of pregabalin in opioid-induced hyperalgesia animals is neither neuropathy-dependent nor reliant on up-regulation of the α₂δ-1 subunit of voltage-gated calcium channels-mechanisms proposed as being essential for pregabalin's efficacy in neuropathy. In opioid-induced hyperalgesia, which extends to colonic distension, a serotonergic facilitatory system may be up-regulated, creating an environment that is permissive for pregabalin-mediated analgesia without peripheral pathology. [ABSTRACT FROM AUTHOR]

The recent high-energy density sodium (Na) metal batteries (SMBs) are restricted by their processability, lifetime, and safety. These issues can be addressed by controlling the reactions at the Na metal by modifying the Na metal anode (SMA) with the sodiophilic hosts. Herein, a multifunctional Na 2 Se/Zn-Mn skeleton is introduced for SMA and fabricate a processable Na@Na 2 Se/Zn-Mn composite using repeated cold rolling/folding approach through the spontaneous reaction between Na metal and ZnMnSe alloy. This unique intermetallic composite has Zn and Mn metal sites for uniform deposition of Na, while Na 2 Se generates a stable SEI for rapid Na + ion transport. It offers outstanding sodiophilicity, high processability, excellent mechanical strength, and high ionic conductivity due to the synergistic effect of multi-component, enabling stable Na plating/stripping at high current densities and areal capacities. An optimized Na 2 Se/Zn-Mn skeleton enables Na||Na symmetric cells to attain a high critical current density of 5.0 mA cm -2 at 5.0 mAh cm -2 with an extended lifespan of 9000 h at 1.0 mA cm -2 at 1.0 mAh cm -2 . Remarkably, when configured into a full cell with a Na 3 V 2 (PO 4 ) 3 cathode, the SMB displays an extended lifespan of 2000 cycles at 10 C and an impressive high-rate capacity of ≈61.6 mAh g - ¹ at 30 C., (© 2024 Wiley‐VCH GmbH.)

Citric acid (CA) is well-known for mitigating cadmium (Cd) toxicity in plants. Yet, the underlying mechanisms driving growth promotion, Cd detoxification/tolerance, and enhanced phytoremediation processes remain incompletely understood. This study investigated the effects of CA application (2.5 mM) on Brassica napus grown in Cd-contaminated (30 mg kg -1 ) growth medium through a controlled pot experiment. Cd exposure alone significantly impaired various plant physiological parameters in B. napus. Whereas CA application significantly (p < 0.05) enhanced physiological attributes, Cd detoxification and tolerance by modulating key genes involved in photosynthesis and Cd transport, including the metal-transporting P 1B -type ATPases (Cd/zinc heavy metal-transporting ATPase 1; HMA1) and light-harvesting chlorophyll a/b-binding 3 (LHCB3). Notably, CA application increased Cd accumulation in stems and leaves by 4% and 35%, respectively, enhancing bioconcentration factors (BCF) by 12% in stems and 40% in leaves while reducing root BCF by 10%. This translocation was facilitated by the upregulation of HMA4, HMA2, and plant Cd resistance (PCR2) genes in plant leaves, improving Cd mobility within the plant. Furthermore, CA induced a 34% increase in phytochelatins and a 32% upregulation in metallothioneins, accompanied by a significant reduction in oxidative stress markers, including a 40% decrease in hydrogen peroxide and a 44% decline in malondialdehyde levels in leaves. Enhanced antioxidant enzyme activity and osmolyte accumulation further contributed to improved Cd detoxification/sequestration in leaves, reduced oxidative stress, and improved photosynthetic efficiency, resulting in enhanced plant biomass production and Cd tolerance. Transcriptomic analysis showed that CA treatment substantially influenced the expression of 12,291 differentially expressed genes (DEGs), with 750 common genes consistently downregulated in CK vs Cd treatment group but upregulated in Cd vs Cd-CA treatment group. Additionally, CA modulated 11 DEGs associated with 32 gene ontologies in the citrate pathway under Cd stress, highlighting its targeted regulatory effect on metabolic pathways involved in Cd stress response. This study offers novel insights into the synergistic role of CA in promoting plant growth and regulating Cd uptake in B. napus, highlighting its potential to enhance phytoremediation strategies., 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 Ltd. All rights reserved.)

Entomopathogenic fungi (EPF) are known for their efficacy in controlling adult mosquito populations by penetrating through their cuticle. However, the effect of oral administration of EPF on the biological parameters of Aedes aegypti and Anopheles stephensi remains largely unexplored. This study aimed to assess the effect of orally administrated EPF isolates on the survival, feeding behavior, fecundity, fertility, follicle development and host-searching behavior in response to yeast-generated CO 2 of Ae. aegypti and An. stephensi. An initial screening of 50 isolates involved exposure of adult Ae. aegypti and An. stephensi by integument inoculation. Subsequently, the entomopathogenic effect of the five highly virulent isolates was confirmed through oral administration revealing Beauveria pseudobassiana 42-51 as a potent mosquito killer. B. pseudobassiana 42-51 was administered orally to evaluate sub-lethal effects. The results showed a 63 % and 43 % reduction in blood feeding of Ae. aegypti and An. stephensi, respectively. Furthermore, a decrease in egg hatching rate was observed, with a reduction of 83% for Ae. aegypti and 74% for An. stephensi on the seventh day following fungal administration, showing decreased hatchability in both species. Poor and abnormal follicle development was observed in both mosquito species. Also, the host-searching behavior was evaluated by attraction to CO 2 utilizing a Y-tube olfactometer. A tendency of reduction in the attraction rate towards the odor was observed three days post-fungal administration. These findings underscore the significant impact of oral administration of B. pseudobassiana 42-51 on mosquitoes, highlighting not only its lethal effects but also sub lethal impacts on their biology. Moreover, this fungus may exhibit the potential to simultaneously control both mosquito species and serve as a biocontrol agent for the management of vector-borne diseases., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Venous thromboembolism is responsible for a significant burden of disease worldwide. Despite the publication of multiple international guidelines, anecdotal evidence suggests significant clinical variation exists in the diagnostic and management pathways of pulmonary embolism (PE). We conducted a retrospective cohort study using electronic medical records to examine clinical variation in patients admitted to a tertiary referral center in Australia with a diagnosis of PE between November 2018 and January 2020. Three hundred cases met the inclusion criteria; we found variation in rates of compression ultrasonography, acute investigation of the right ventricle, and planning of repeat imaging at specialist follow-up. Guidelines do not address the use of compression ultrasonography in already diagnosed PE, are conflicting in their recommendation for acute investigation of the right ventricle, and recommend repeat imaging only if there are persistent symptoms at the time of specialist follow-up. The variations we found in this study may in part be due to physician preference or due to the paucity of evidence for some of these diagnostic practices. Robust future studies are required to guide the use of these investigations in PE., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Devesh Thakkar et al.)

2D transitional metal selenide heterostructures are promising electrode materials for potassium-ion batteries (PIBs) owing to the large surface area, high mechanical strength, and short diffusion pathways. However, the cycling performance remains a significant challenge, particularly concerning the electrochemical conversion reaction. Herein, 2D Se-rich ZnSe/CoSe 2 @C heterostructured composite is fabricated via a convenient hydrothermal approach followed by selenization process, and then applied as high-performance anodes for PIBs. For example, the capacity delivered by the heterostructured composite is mainly contributed to the synergistic effect of conversion and alloy/de-alloy processes aroused by K + , where K + may highly insert or de-insert into Se-rich ZnSe/CoSe 2 @C. The obtained electrode delivers an outstanding reversible charge capacity of 214 mA h g -1 at 1 A g -1 after 4000 cycles for PIBs, and achieves 262 mAh g -1 when coupled with a PTCDA cathode in the full cell. The electrochemical conversion mechanism of the optimized electrode during cycling is investigated through in situ XRD, Raman, and ex situ HRTEM. In addition, the heterostructured composite as anodes also displays excellent electrochemical performances for sodium-ion batteries (SIBs) and lithium-ion batteries (LIBs). This work opens up a new window for investigating novel electrode materials with excellent capacity and long durability., (© 2024 Wiley‐VCH GmbH.)

Conversion and alloying-type transitional metal sulfides have attracted significant interests as anodes for Potassium-ion batteries (PIBs) and Sodium-ion batteries (SIBs) due to their high theoretical capacities and low cost. However, the poor conductivity, structural pulverization, and high-volume expansions greatly limit the performance. Herein, Co 1-x S/ZnS hollow nanocube-like heterostructure decorated on reduced graphene oxide (Co 1-x S/ZnS@rGO) composite is fabricated through convenient hydrothermal and post-heat vulcanization techniques. This unique composite can provide a more stable conductive network and shorten the diffusion length of ions, which exhibits a remarkable initial charge capacity of 638.5 mA h g -1 at 0.1 A g -1 for SIBs and 606 mA h g -1 at 0.1 A g -1 for PIBs, respectively; It is worth noting that the composite presents remarkable long stable cycle performance in PIBs, which initially delivered 274 mA h g -1 and sustained the charge capacity up to 245 mA h g -1 at high current density of 1 A g -1 after 2000 cycles. A series of in situ/ex situ detections and first principle calculations further validate the high potassium ions adsorption ability of Co 1-x S/ZnS anode materials with high diffusion kinetics. This work will accelerate the fundamental construction of bimetallic sulfide hollow nanocubes heterostructure electrodes for energy storage applications., (© 2024 Wiley‐VCH GmbH.)

Mn-based fluorophosphates have attracted much attention as cathodes for sodium-ion batteries owing to their high cost effectiveness, considerable capacity, and stable framework. However, the fascinating Mn 3+/2+ redox couple suffers from inadequate activation due to the Mn-O covalent character and poor electronic conductivity, impeding its further applications. Herein, a local electronic structure regulation strategy is proposed to improve the Mn 3+/2+ redox potential and reversible capacity simultaneously through introducing elements with low-energy 3d orbitals to expand the energy gap between the e g orbitals and Fermi energy of Na. Moreover, the 3d element substitution serves to narrow the band gap toward the improved intrinsic electronic conductivity. In comparison with pristine Na 2 Fe 0.45 Mn 0.55 PO 4 F, the as-prepared Na 2 Fe 0.45 Mn 0.4 V 0.1 PO 4 F cathode achieves an increase from 3.5 to 3.6 V in the high-voltage platform and an improvement in energy density from 330 to 361 Wh kg -1 . This work inspires new ideas in adjusting the redox potential of polyanionic cathodes through deliberate regulation of the local electronic structure.

Fusarium solani KMZW-1 is recognized for its potential as a biocontrol agent against agricultural and forestry pests, particularly due to its compatibility with integrated pest management (IPM) strategies. This study aimed to investigate the complete genome of F. solani KMZW-1 and assess its pathogenicity against Bactrocera dorsalis . Whole-genome sequencing revealed a genome size of 47,239,278 bp, comprising 27 contigs, with a GC content of 51.16% and fungus identified as F. solani KMZW-1. The genome completeness was assessed as 97.93% using BUSCO analysis, the DFVF sequence identifier was Fusarium 0G092560.1, and AntiSMASH analysis identified 35 gene clusters associated with secondary metabolite biosynthesis, providing insights into the genetic basis of its pathogenic mechanisms and biocontrol potential. Comparative genomic analysis found 269 unique genes for F. solani KMZW-1, and collinearity analysis exhibited a high degree of synteny with Fusarium solani-melongenae . The pathogenicity of F. solani KMZW-1 was assessed using concentrations ranging from 1 × 10 4 to 1 × 10 11 conidia/mL. Higher concentrations (1 × 10 10 to 1 × 10 11 conidia/mL) resulted in significantly increased cumulative mortality rates of B. dorsalis adults compared to the control group. Notably, the pathogenicity was higher in male adults than in females. Probit analysis yielded LC 50 (50% lethal concentration) values of 5.662 for female and 4.486 for male B. dorsalis adults. In summary, F. solani , KMZW-1 exhibits strong insecticidal activity against B. dorsalis and shows potential as a biocontrol agent with IPM strategies. These findings provide robust genomic evidence supporting the use of F. solani KMZW-1 in managing against B. dorsalis populations.

Objective To determine the frequency of false-negative mammograms, and identify the factors contributing to missed breast cancer diagnoses in Pakistani women. Materials and methods This descriptive, prospective cross-sectional study was conducted at a tertiary care hospital from December 15, 2020, to December 10, 2023, including 150 women aged 30 to 60 who underwent bilateral mammography and concurrent breast ultrasound. The study analyzed the frequency and causes of false negatives, categorizing them into patient-related, tumor-related, technical-related, and provider-related factors. Stratification was performed based on age groups and Breast Imaging Reporting and Data System (BI-RADS) scores, and statistical significance was assessed using Chi-square tests. Results The study found a 5.1% frequency of false-negative mammograms. Lesion-related factors were seen in 59 (39.7%) patients; patient-related factors were seen in 40 (26.7%) patients; provider-related factors were seen in 29 (19.3%) patients; and technical-related factors were seen in 22 (26.7%) patients. Conclusion Dense breast tissue significantly contributes to missed breast cancer diagnoses in Pakistani women. While lesion-related, provider-related, and technical-related factors uniformly affect mammography outcomes, addressing patient-specific challenges - particularly in younger women with dense breasts - is crucial. The study suggests incorporating supplementary imaging modalities, like ultrasound, in routine screening for better detection, potentially informing national breast cancer screening guidelines in Pakistan., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. IRB/EC INMOL-AECH issued approval INMOL-53-(42). Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Malik et al.)

In this study, we prepared a hybrid film incorporating the MnFeO 3 -decorated conducting two-dimensional (2D) MXene sheet-suspended [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) electron transfer layer (ETL) for the perovskite solar cells (PSCs) and detectors. The incorporation of MXene-MnFeO 3 with the PCBM ETL could drive exceptional conducting features for the PSCs. Moreover, the presence of MXene-MnFeO 3 facilitated superior charge transfer pathways, thereby enhancing the electron extraction and collection processes. This enhancement was directed to improve the electron mobility within the device, resulting in high photocurrents. The designed interface engineering with the MXene-MnFeO 3 nanocomposite-tuned PCBM ETL has produced a remarkable power conversion efficiency of 17.79% ± 0.27. Moreover, X-ray detectors employing PCBM modulated with the MXene-MnFeO 3 ETL achieved notable performance metrics including 18.47 μA/cm 2 CCD-DCD, 5.53 mA/Gy·cm 2 sensitivity, 7.64 × 10 -4 cm 2 /V·s electron mobility, and 1.51 × 10 15 cm 2 /V·s trap density.

Our study investigates vertebral fractures in individuals with distal radius fractures. Among 512 patients, 41.21% had vertebral fractures, predominantly in the lumbar spine. These findings highlight the importance of screening for vertebral fractures in this population, informing early intervention strategies to mitigate risks associated with osteoporosis., Purpose: This study's main goal was to look into the frequency, location, kind, and severity of asymptomatic vertebral fragility fractures (VFF) in people who had fractures of the fragility of the distal radius. Although VFF is frequently misdiagnosed, it is linked to higher mortality, morbidity, and hip fracture risk. The study also attempted to investigate the relationship between VFF and certain demographic and lifestyle factors, as well as FRAX data, in this patient population., Methods: Between January, 2021, and January, 2022, individuals with low-energy distal radial fractures who presented to the emergency room of tertiary care hospital of Karachi, Pakistan, were the subject of a cross-sectional study and were 45 years of age or older except those who fitted the exclusion criteria (n = 208). The thoracic and/or lumbar spine was imaged using radiology, and information on demographics, way of life, and FRAX (Fracture Risk Assessment Tool) was gathered. Using the Genant semiquantitative approach, an impartial and blinded orthopaedist identified VF in the images and determined their severity. SPSS version 20 was used to analyse the data., Results: Two hundred eleven (41.21%) of them were found to have radiographic VFF and only 12 (2.34%) of the 512 patients who were tested were getting osteoporotic therapy. The thoracic spine (32.7%), followed by the lumbar spine (43.12%), was the area most frequently afflicted. In 24.17% of the patients, multiple fractures of the thoracolumbar spine were found. The wedge form (54.5%), followed by biconcave (30.81%) and crush (14.7%), was the most prevalent VFF type. The majority of detected VFF were rated as having a 25-40% height loss (64.9%) then severe (> 40%) fractures (35.1%), according to the Genant grading method. Notably, there were no variations in smoking, drinking, BMI, or FRAX score between patients with and without VFF that were statistically significant., Conclusion: Based on our study's findings, it is clear that osteoporotic vertebral fragility fractures occur in almost half of individuals with distal radius fractures. The lumbar spine is notably the most affected region, predominantly with wedge fractures. Given the high prevalence of asymptomatic vertebral fragility fractures (VFF), proactive measures are necessary to mitigate associated risks. Prioritising comprehensive fall risk assessments for these patients and interventions to enhance bone mineral density and strength are crucial. Early identification of asymptomatic VFF enables timely intervention, optimising patient care and minimising the risk of complications in this vulnerable population., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

The rapid advancement of nanotechnology has sparked much interest in applying nanoscale perovskite materials for photodetection applications. These materials are promising candidates for next-generation photodetectors (PDs) due to their unique optoelectronic properties and flexible synthesis routes. This review explores the approaches used in the development and use of optoelectronic devices made of different nanoscale perovskite architectures, including quantum dots, nanosheets, nanorods, nanowires, and nanocrystals. Through a thorough analysis of recent literature, the review also addresses common issues like the mechanisms underlying the degradation of perovskite PDs and offers perspectives on potential solutions to improve stability and scalability that impede widespread implementation. In addition, it highlights that photodetection encompasses the detection of light fields in dimensions other than light intensity and suggests potential avenues for future research to overcome these obstacles and fully realize the potential of nanoscale perovskite materials in state-of-the-art photodetection systems. This review provides a comprehensive overview of nanoscale perovskite PDs and guides future research efforts towards improved performance and wider applicability, making it a valuable resource for researchers., (© 2024. The Author(s).)

Digital therapeutics have evolved rapidly with technological advances in healthcare. Despite their increasing use, gaps remain in understanding their regulatory frameworks, integration, and efficacy for conditions like substance use disorder, insomnia, attention deficit hyperactivity disorder, and post-traumatic stress disorder. This study evaluates FDA-approved digital therapeutics and explores their potential to revolutionize psychiatric treatments amid ongoing technological and regulatory changes. We conducted a comprehensive review of major databases, focusing on articles published up to January 2024 on FDA-approved digital therapeutics. We excluded non-English articles and those lacking empirical data or focusing on non-FDA-approved therapeutics. Our analysis covered regulatory compliance, clinical outcomes, and integration with traditional treatments. The review of nine FDA-cleared digital therapeutics revealed benefits like improved treatment accessibility and potential reductions in healthcare costs. For example, Somryst, a cognitive-behavioral therapy-based treatment for insomnia, showed that over 40 percent of users overcame chronic insomnia, and 60 percent experienced improvements without adverse effects. However, challenges remain, including low provider adoption, inadequate insurance coverage, and high user dropout rates. While digital therapeutics enhance accessibility, they face regulatory challenges, reimbursement issues, and the need for robust clinical evidence. Success depends on collaboration among stakeholders to demonstrate value, ensure safety, and integrate them into existing healthcare systems., Competing Interests: The authors report no conflicts of interest.

Laser-induced graphene (LIG) and Laser-scribed graphene (LSG) are both advanced materials with significant potential in various applications, particularly in the field of sustainable sensors. The practical uses of LIG (LSG), which include gas detection, biological process monitoring, strain assessment, and environmental variable tracking, are thoroughly examined in this review paper. Its tunable characteristics distinguish LIG (LSG), which is developed from accurate laser beam modulation on polymeric substrates, and they are essential in advancing sensing technologies in many applications. The recent advances in LIG (LSG) applications include energy storage, biosensing, and electronics by steadily advancing efficiency and versatility. The remarkable flexibility of LIG (LSG) and its transformative potential in regard to sensor manufacturing and utilization are highlighted in this manuscript. Moreover, it thoroughly examines the various fabrication methods used in LIG (LSG) production, highlighting precision and adaptability. This review navigates the difficulties that are encountered in regard to implementing LIG sensors and looks ahead to future developments that will propel the industry forward. This paper provides a comprehensive summary of the latest research in LIG (LSG) and elucidates this innovative material's advanced and sustainable elements.

Cancer pain is a growing problem, especially with the substantial increase in cancer survival. Reports indicate that bone metastasis, whose primary symptom is bone pain, occurs in 65-75% of patients with advanced breast or prostate cancer. We optimized a preclinical in vivo model of cancer-induced bone pain (CIBP) involving the injection of Lewis Lung Carcinoma cells into the intramedullary space of the femur of C57BL/6 mice or transgenic mice on a C57BL/6 background. Mice gradually reduce the use of the affected limb, leading to altered weight bearing. Symptoms of secondary cutaneous heat sensitivity also manifest themselves. Following optimization, three potential analgesic treatments were assessed; 1) single ion channel targets (targeting the voltage-gated sodium channels Na V 1.7, Na V 1.8, or acid-sensing ion channels), 2) silencing µ-opioid receptor-expressing neurons by modified botulinum compounds, and 3) targeting two inflammatory mediators simultaneously (nerve growth factor (NGF) and tumor necrosis factor (TNF)). Unlike global Na V 1.8 knockout mice which do not show any reduction in CIBP-related behavior, embryonic conditional Na V 1.7 knockout mice in sensory neurons exhibit a mild reduction in CIBP-linked behavior. Modified botulinum compounds also failed to cause a detectable analgesic effect. In contrast, inhibition of NGF and/or TNF resulted in a significant reduction in CIBP-driven weight-bearing alterations and prevented the development of secondary cutaneous heat hyperalgesia. Our results support the inhibition of these inflammatory mediators, and more strongly their dual inhibition to treat CIBP, given the superiority of combination therapies in extending the time needed to reach limb use score zero in our CIBP model., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: John N Wood reports financial support was provided by Cancer Research UK. 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., (© 2024 The Author(s).)

Physical exercise is increasingly recognized for its potential therapeutic effects in individuals with substance use disorders (SUDs), particularly in terms of relapse prevention, mental health improvement, and enhanced quality of life (QoL). This systematic review aimed to statistically summarize findings from numerous randomized controlled trials (RCTs) on the effects of physical exercise on mental health outcomes, QoL, abstinence-related outcomes, and cravings among SUD patients. A systematic search was conducted across PubMed, Web of Science, and Scopus databases, resulting in the inclusion of 15 studies, comprising RCTs, cohort studies, observational studies, and quasi-experimental designs. The review revealed a significant reduction in stress and depression, with a standardized mean difference (SMD) of 0.63, indicating a moderate effect size. Patients engaging in physical exercise reported a higher QoL across various domains, although the trend toward reduced cravings was not statistically significant, suggesting a need for further research in this area. The findings suggest that physical exercise can positively contribute to the treatment of SUD patients by enhancing mental health and QoL., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Nazmin et al.)

The increasing prevalence of coal mine dust-related lung diseases in coal miners calls for urgent and meticulous scrutiny of airborne respirable coal mine dust (RCMD), specifically focusing on particles at the nano-level. This necessity is driven by expanding research, including the insights revealed in this paper, that establish the presence and significantly increased toxicity of nano-sized coal dust particles in contrast to their larger counterparts. This study presents an incontrovertible visual proof of these tiny particulates in samples collected from underground mines, utilizing advanced techniques such as scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS). The intricate elemental composition of nano-sized coal dust identified through EDS analysis reveals the presence of elements such as silica and iron, which are known to contribute to lung pathologies when inhaled over prolonged periods. The outcomes of the statistical analyses reveal significant relationships between particle size and elemental composition, highlighting that smaller particles tend to have higher carbon content, while larger particles exhibit increased concentrations of elements like silica and aluminum. These analyses underscore the complex interactions within nano-sized coal dust, providing critical insights into their behavior, transport, and health impacts. The nano-sized coal dust could invade the alveoli, carrying these toxic elements from where they are impossible to exhale. The revelation of nano-sized coal dust's existence and the associated health hazards necessitate their incorporation into the regulatory framework governing the coal mining industry. This study lays the groundwork for heightened protective measures for miners, urging the invention of state-of-the-art sampling instruments, comprehensive physicochemical profiling of RCMD nanoparticles, and the pursuit of groundbreaking remedies to neutralize their toxic impact. These findings advocate for a paradigm shift in how the coal mining industry views and handles particulate matter, proposing a re-evaluation of occupational health standards and a call to action for protecting coal miners worldwide., 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 peel stripe margin pattern is one of the most important quality traits of watermelon. In this study, two contrasted watermelon lines [slb line (P 1 ) with a clear peel stripe margin pattern and GWAS-38 line (P 2 ) with a blurred peel stripe margin pattern] were crossed, and biparental F 2 mapping populations were developed. Genetic segregation analysis revealed that a single recessive gene is modulating the main-effect genetic locus ( Clcsm ) of the clear stripe margin pattern of peel. Bulked segregant analysis-based sequencing (BSA-Seq) and fine genetic mapping exposed the delimited Clcsm locus to a 19.686-kb interval on chromosome 6, and the Cla97C06G126680 gene encoding the MYB transcription factor family was identified. The gene mutation analysis showed that two non-synonymous single-nucleotide polymorphism (nsSNP) sites [Chr6:28438793 (A-T) and Chr6:28438845 (A-C)] contribute to the clear peel stripe margin pattern, and quantitative real-time polymerase chain reaction (qRT-PCR) also showed a higher expression trend in the slb line than in the GWAS-38 line. Further, comparative transcriptomic analysis identified major differentially expressed genes (DEGs) in three developmental periods [4, 12, and 20 days after pollination (DAP)] of both parental lines. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses indicated highly enriched DEGs involved in metabolic processes and catalytic activity. A total of 44 transcription factor families and candidate genes belonging to the ARR-B transcription factor family are believed to regulate the clear stripe margin trait of watermelon peel. The gene structure, sequence polymorphism, and expression trends depicted significant differences in the peel stripe margin pattern of both parental lines. The ClMYB36 gene showed a higher expression trend for regulating the clear peel stripe margin of the slb line, and the ClAPRR5 gene depicted a higher expression for modulating the blurred peel stripe margin in the GWAS-38 line. Overall, our fine genetic mapping and transcriptomic analysis revealed candidate genes differentiating the clear and blurred peel stripe patterns of watermelon fruit., 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 Yang, Amanullah, Duan, Guo, Xu, Bao, An, Yuan, Liu, Liu, Gao, Zhao, Li and Gao.)

Background: Tumour thrombus of the facial vein is an exceedingly rare complication arising from mucoepidermoid carcinoma of the salivary glands. Early detection is pivotal for appropriate management, as delays can lead to metastatic disease, worsening the prognosis., Case Description: We present a case involving a 76-year-old male with a history of mucoepidermoid carcinoma of the right submandibular gland, previously treated with surgical resection and radiotherapy. The patient, a long-term worker in a rubber factory, presented with a painless, firm swelling in the right cheek, persisting for three months. Contrast-enhanced computed tomography (CECT) showed distended facial vein with enhancing thrombus confirmed by sonographic correlation demonstrating intralesional vascularity. Cannon ball pulmonary nodules were also noted. Radiological findings led to a core biopsy, confirming tumor thrombosis of the facial vein due to mucoepidermoid carcinoma. However, the patient declined a biopsy of the pulmonary nodules, and has been referred to oncology for further management., Conclusions: This case highlights the critical importance of considering venous tumour thrombus in patients with previous salivary gland malignancies presenting with new or persistent facial swellings. It emphasises the role of advanced imaging techniques in the early identification of this rare entity. Additionally, it stresses the need for healthcare providers to engage in thorough discussions with patients about the potential consequences of forgoing recommended treatments, reinforcing the need for vigilance in monitoring such patients., Learning Points: Tumours of head and neck may cause thrombosis of veins by direct invasion resulting in a tumour thrombus, or indirectly by exerting a mass effect and vein compression.These can be distinguished by contrast-enhanced computed tomography (CECT) or magnetic resonance imaging (MRI).Doppler ultrasound may show patchy neovascularisation in a tumour thrombus, which would be absent if thrombosis was caused by compression., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2024.)

Epilepsy is one of the most frequent neurological illnesses caused by epileptic seizures and the second most prevalent neurological ailment after stroke, affecting millions of people worldwide. People with epileptic disease are considered a category of people with disabilities. It significantly impairs a person's capacity to perform daily tasks, especially those requiring focusing or remembering. Electroencephalogram (EEG) signals are commonly used to diagnose people with epilepsy. However, it is tedious, time-consuming, and subjected to human errors. Several machine learning techniques have been applied to recognize epilepsy previously, but they have some limitations. This study proposes a deep neural network (DNN) machine learning model to determine the existing limitations of previous studies by improving the recognition efficiency of epileptic disease. A public dataset is used in this study and classified into training and testing sets. Experiments were performed to evaluate the DNN model with different dataset classification ratios (80:20), (70:30), (60:40), and (50:50) for training and testing, respectively. Results were evaluated by using different performance metrics including validations, and comparison processes that allow the assessment of the model's effectiveness. The experimental results showed that the overall efficiency of the proposed model is the highest compared with previous works, with an accuracy rate of 97%. Thus, this study is more accurate and efficient than the existing seizure detection approaches. DNN model has great potential for recognizing epileptic patient activity using a numerical EEG dataset offering a data-driven approach to improve the accuracy and reliability of seizure detection systems for the betterment of patient care and management of epilepsy., 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 Khurshid, Wahid, Ali, Gumaei, Alzanin and Mosleh.)

Purpose: Patients with Waldenström macroglobulinemia (WM) have disparate outcomes. Newer therapies have emerged since the development of International Prognostic Scoring System, and MYD88 L265P mutation is now frequently assessed at diagnosis, warranting reexamination of the prognostic parameters., Patients and Methods: We reviewed records of 889 treatment-naïve patients with active WM, consecutively seen between January 01, 1996, and December 31, 2017, to identify clinical predictors of overall survival (OS) in univariate analyses. Patients with complete data for the parameters significant on the univariate analyses (n = 341) were included in a multivariable analysis to derive a prognostic model, subsequently validated in a multi-institutional cohort., Results: In the derivation cohort (n = 341), age (hazard ratio [HR], 1.9 [95% CI, 1.2 to 2.1]; P = .0009), serum lactate dehydrogenase (LDH) above upper limit of normal (HR, 2.3 [95% CI, 1.3 to 4.5]; P = .007), and serum albumin <3.5 g/dL (HR, 1.5 [95% CI, 0.99 to 2.3]; P = .056) were independently prognostic. By assigning a score of 1 point each to albumin <3.5 g/dL (HR, 1.5) and age 66-75 years (HR 1.4) and 2 points for age >75 years (HR, 2.6) or elevated LDH (HR, 2.3), four groups with distinct outcomes were observed on the basis of the composite scores. Five-year OS was 93% for the low-risk (score 0), 82% for low-intermediate risk (score 1), 69% for intermediate-risk (score 2), and 55% for the high-risk (score ≥3; P < .0001) groups. In the validation cohort (N = 335), the model maintained its prognostic value, with a 5-year OS of 93%, 90%, 75%, and 57% for the four groups, respectively ( P < .0001)., Conclusion: Modified Staging System for WM (MSS-WM), utilizing age, albumin, and LDH is a simple, clinically useful, and externally validated prognostic model that reliably risk-stratifies patients with symptomatic WM into four groups with distinct prognosis.

Yunnan semi-fine wool (YSFW) is a recently developed dual-purpose (meat and wool) sheep breed mainly found in Yunnan Province, China. Moreover, dietary calcium is essential for animal health and productivity. The current experiment aimed to investigate the impact of dietary calcium on sheep gut metabolite profile. For this, thirty YSFW rams (male, age = 10 months, and body weight = 40.37 ± 0.49 kg) were randomized into three groups (n = 10 rams/group), followed by a completely randomized design, and the groups were allotted to one of three dietary calcium levels (Q&#95;1 = 0.50%, Q&#95;3 = 0.73%, and Q&#95;5 = 0.98% on a dry basis). The rams were fed ad libitum by feeding twice a day (at 08:00 and 17:00 h/day) throughout the experimental period (44 day). On the 21st day of the experiment, fecal samples were collected from 27 rams (9/group) and untargeted metabolite profiling was performed by using ultra-performance liquid chromatography. The PCA plot showed that the Q&#95;5 group metabolites were clustered more tightly than for Q&#95;1 and Q&#95;3, respectively. The tightly clustering molecules were mainly alkaloids and their derivatives, benzenoids, lignans and related compounds, lipids, nucleotides, organic acids, and nitrogenous-based derivatives. According to the Kyoto Encyclopedia of Genes and Genomes pathway analysis, these molecules potentially contribute to metabolic pathways, biosynthesis of secondary metabolites, proteinaceous compounds, and the metabolism of the protein derivatives, particularly amino acids. The PLS-DA plots revealed a significant difference between the Q&#95;1, Q&#95;3, and Q&#95;5 groups, suggesting that Q&#95;5 had a clear separation across the groups. Based on the metabolomic analysis, feeding different levels of dietary calcium significantly changed the metabolomic profile of YSFW rams, which primarily entails metabolic pathways such as energy, protein, and lipid metabolism.

Layered oxides of sodium-ion batteries suffer from severe side reactions on the electrode/electrolyte interface, leading to fast capacity degradation. Although surface reconstruction strategies are widely used to solve the above issues, the utilization of the low-cost wet chemical method is extremely challenging for moisture-sensitive Na-based oxide materials. Here, the solvation tuning strategy is proposed to overcome the deterioration of NaNi 1/3 Mn 1/3 Fe 1/3 O 2 in water-based solution and conduct the surface reconstruction. When capturing the water molecules by the solvation structure of cations, here is Li + , the structural collapse and degradation of layered oxides in water-based solvents are greatly mitigated. Furthermore, Li(H 2 O) 3 EA + promotes the profitable Li + /Na + exchange to build a robust surface, which hampers the decomposition of electrolytes and the structural evolution upon cycling. Accordingly, the lifespan of Li-reinforced materials is prolonged to three times that of the pristine one. This work represents a step forward in understanding the surface reconstruction operated in a water-based solution for high-performance sodium layered oxide cathodes., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

The heterostructure of transition-metal chalcogenides is a promising approach to boost alkali ion storage due to fast charge kinetics and reduction of activation energy. However, cycling performance is a paramount challenge that is suffering from poor reversibility. Herein, it is reported that Se-rich particles can chemically interact with local hexagonal ZnSe/MnSe@C heterostructure environment, leading to effective ions insertion/extraction, enabling high reversibility. Enlightened by theoretical understanding, Se-rich particles endow high intrinsic conductivities in term of low energy barriers (1.32 eV) compared with those without Se-rich particles (1.50 eV) toward the sodiation process. Moreover, p orbitals of Se-rich particles may actively participate and further increase the electronegativity that pushes the Mn d orbitals (dxy and dx 2 -y 2 ) and donate their electrons to dxz and dyz orbitals, manifesting strong d-d orbitals interaction between ZnSe and MnSe. Such fundamental interaction will adopt a well-stable conducive electronic bridge, eventually, charges are easily transferred from ZnSe to MnSe in the heterostructure during sodiation/desodiation. Therefore, the optimized Se-rich ZnSe/MnSe@C electrode delivered high capacity of 576 mAh g -1 at 0.1 A g -1 after 100 cycles and 384 mAh g -1 at 1 A g -1 after 2500 cycles, respectively. In situ and ex situ measurements further indicate the integrity and reversibility of the electrode materials upon charging/discharging., (© 2024 Wiley‐VCH GmbH.)