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The sluggish redox reaction kinetics and "shuttle effect" of lithium polysulfides (LPSs) impede the advancement of high-performance lithium-sulfur batteries (LSBs). Transition metal phosphides exhibit distinctive polarity, metallic properties, and tunable electron configuration, thereby demonstrating enhanced adsorption and electrocatalytic capabilities towards LPSs. Consequently, they are regarded as exceptional sulfur hosts for LSBs. Moreover, the introduction of a heterogeneous structure can enhance reaction kinetics and expedite the transport of electrons/ions. In this study, a composite of hollow CoP-FeP cubes with heterostructure modified carbon nanotube (CoFeP-CNTs) was fabricated and utilized as sulfur host in advanced LSBs. The presence of carbon nanotubes (CNTs) facilitates enhanced electron and Li + transport. Meanwhile, the active sites within the heterogeneous interface of CoP-FeP suppress the "shuttle effect" and enhance the conversion kinetics of LPSs. Therefore, the CoFeP-CNTs/S electrode exhibited exceptional cycling stability and demonstrated a capacity attenuation of merely 0.051 % per cycle over 600 cycles at 1C. This study presents a highly effective tactic for synthesizing dual-acting transition metal phosphides with heterostructure, which will play a pivotal role in advancing the development of efficient LSBs., 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.)

Identifying multiexciton states generated from singlet fission is key to understanding the carrier multiplication process, which presents a strategy for improving the efficiency of photovoltaics and bioimaging. Broadband optically detected magnetic resonance (ODMR) is a sensitive technique to detect multiexciton states. Here, we report a dominant species a weakly exchange coupled triplet pair located on adjacent molecules oriented by nearly 90° (V2) under intense light excitation, contrasting to the π-stacked triplet pair under low excitation intensity. The weakly coupled species model precisely reproduces the intricate spin transitions in the Hilbert space of the triplet pair. Combining the magneto-photoluminescence and high-magnetic-field ODMR, we also identify a strongly exchange-coupled state of three triplet excitons formed by photoexcited V2, which manifests through the magnetic-field-induced level crossings between its quintet and triplet manifolds. Our findings demonstrate the microscopic picture of different multiexciton states and the possible transitions among them during exciton fission, which provide insight for the further molecular designs for fission materials.

Bisphenol A (BPA) is a well-recognized endocrine-disrupting chemical that poses risks to both human health and the environment. Laccase can effectively biodegrade bisphenol A, but the low environmental temperature (∼25 °C) restricts the biodegradation efficiency. In this study, the enzyme laccase and Fe 3 O 4 with solar-thermal conversion capability were coimmobilized into zeolitic imidazolate framework-8 (Lac@ZIF-8-Fe 3 O 4 ) to facilitate efficient biodegradation of bisphenol A under simulated solar irradiation. Compared to free laccase, Lac@ZIF-8-Fe 3 O 4 exhibited high activity recovery (115.5%), an ∼39% increased catalytic constant, more effective bisphenol A biodegradation (up to 24-fold) at extensive bisphenol A concentrations (5-100 mg/L), excellent thermal stability (50 °C, 12 h), acid-tolerance (pH 3), and storage ability in 10 days. Simulated solar irradiation (1 kW/m 2 ) increased the temperature of Lac@ZIF-8-Fe 3 O 4 solution (10 μg laccase/mL) from 25 to 42.5 °C within 15 min, resulting in 96.4% biodegradation of bisphenol A within 60 min, nearly double the biodegradation efficiency under dark condition (55.9%). Furthermore, Lac@ZIF-8-Fe 3 O 4 maintained 99.0% biodegradation efficiency even after 12 recycles of use under simulated solar irradiation (5 mg/L bisphenol A, 80 min/cycle). This work has thus offered efficient biocatalysis for integrating solar-energy promotion and enzymatic catalysis in treating environmental BPA pollutants. Further, the experimental findings benefited from the development of more sustainable and high-performance immobilized enzyme preparations for pollutant treatment via solar-thermal promotions.

Mosquitoes within the Culex pipiens complex play a crucial role in human disease transmission. Insecticides, especially pyrethroids, are used to control these vectors. Mosquito legs are the main entry point and barrier for insecticides to gain their neuronal targets. However, the resistance mechanism in mosquito legs is unclear. Herein, we employed transcriptomic analyses and isobaric tags for relative and absolute quantitation techniques to investigate the resistance mechanism, focusing on Cx. pipiens legs. We discovered 2346 differentially expressed genes (DEGs) between deltamethrin-resistant (DR) and deltamethrin-sensitive (DS) mosquito legs, including 41 cytochrome P450 genes. In the same comparison, we identified 228 differentially expressed proteins (DEPs), including six cytochrome P450 proteins. Combined transcriptome and proteome analysis revealed only two upregulated P450 genes, CYP325G4 and CYP6AA9 . The main clusters of DEGs and DEPs were associated with metabolic processes, such as cytochrome P450-mediated metabolism of drugs and xenobiotics. Transcription analysis revealed high CYP325G4 and CYP6AA9 expression in the DR strain at 72 h posteclosion compared with that in the DS strain, particularly in the legs. Mosquitoes knocked down for CYP325G4 were more sensitive to deltamethrin than the controls. CYP325G4 knockdown reduced the expression of several chlorinated hydrocarbon (CHC)-related genes, which altered the cuticle thickness and structure. Conversely, CYP6AA9 knockdown increased CHC gene expression without altering cuticle thickness and structure. P450 activity analysis demonstrated that CYP325G4 and CYP6AA9 contributed to metabolic resistance in the midgut and legs. This study identified CYP325G4 as a novel mosquito deltamethrin resistance factor, being involved in both metabolic and cuticular resistance mechanisms. The previously identified CYP6AA9 was investigated for its involvement in metabolic resistance and potential cuticular resistance in mosquito legs. These findings enhance our comprehension of resistance mechanisms, identifying P450s as promising targets for the future management of mosquito vector resistance, and laying a theoretical groundwork for mosquito resistance management.

To evaluate the effects of cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and cytochrome P450 family 2 subfamily C member 19 (CYP2C19) polymorphisms on the plasma concentrations, efficacy, and safety of lacosamide (LCM) among pediatric patients with epilepsy. This prospective study was conducted at two institutions. It included 215 pediatric patients with epilepsy who were under LCM. LCM plasma concentrations were quantified using validated ultra-performance liquid chromatography. CYP2C9 and CYP2C19 polymorphisms were analyzed in all pediatric patients in our hospital's Institute of Clinical Pharmacy research laboratory through polymerase chain reaction, agarose gel electrophoresis detection, gel recovery, and other steps. Seizure frequencies were recorded 3, 6, and 12 months after initiating LCM therapy and compared with the baseline monthly frequency. Clinical information, including efficacy, toxicity, and concomitant drugs, was collected. A total of 158 pediatric patients (73.5%) responded to LCM therapy. Of them, 77 patients reported adverse events while under LCM. The LCM plasma concentration was linearly correlated with its daily dose (r = 0.26, p < 0.001). Patients with adverse events reported higher LCM plasma concentrations (7.9 ± 4.0 µg/mL) than patients without adverse events (6.8 ± 3.0 µg/mL; p < 0.05). The poor metabolizer (PM) group demonstrated the highest concentration-to-dose ratio (1.7 ± 0.7 μg·mL -1 ·kg·mg -1 ) than the extensive metabolizer, intermediate metabolizer, and ultra-rapid metabolizer groups (0.8 ± 0.4, 1.0 ± 0.5, and 0.8 ± 0.4 μg·mL -1 ·kg·mg -1 , respectively). The PM group comprised the highest proportion of patients with effective LCM (9/11, 81.8%) and adverse events (7/11, 63.6%)., Conclusion: LCM plasma concentrations were strongly associated with its clinical efficacy and toxicity. CYP2C19 polymorphisms affect the plasma concentration and treatment efficacy in pediatric patients with epilepsy. CYP2C19 PMs with two no-function alleles are likely to have higher LCM plasma concentrations., What Is Known: • LCM is metabolized by CYP2C19, CYP2C9, and CYP3A4 into pharmacologically inactive O-desmethyl-lacosamide; it primarily undergoes renal elimination. • Plasma LCM concentrations in patients treated with the recommended dose vary widely between and within individuals variability., What Is New: • CYP2C19 polymorphisms affect the plasma concentration and treatment efficacy in Chinese pediatric patients with epilepsy. • CYP2C19 PMs with two no-function alleles are likely to have higher plasma LCM concentrations., Competing Interests: Declarations. Ethics approval: This study was conducted in accordance with the Declaration of Helsinki’s principles. This study was authorized by the Medical Ethics Committee of People’s Hospital of Xinjiang Uygur Autonomous Region (No. KY2019120614), and informed consent was obtained from individual participants and their parents. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Nanoplastics (NPs) exposure could disrupt the synthesis of steroid hormones, thereby posing a potential threat to male reproductive health. However, the existing comprehension of the molecular mechanisms participating in this process remains limited, and the reversibility of NPs-triggered male reproductive toxicity is poorly understood. This investigation focused on the impact of histone modification on testosterone production in mice under long-term exposure to environmentally relevant doses of polystyrene nanoplastics (PS-NPs). The results showed 500 nm and 100 nm PS-NPs could accumulate in mouse testis, with a subsequent significant decrease following a period of self-recovery. The testosterone levels significantly increased after exposure to 500 nm and 100 nm PS-NPs, and the protein levels of CYP11A1, CYP17A1, and 17β-HSD were upregulated. Furthermore, PS-NPs exposure decreased the levels of multiple histone modifications (H3K9me1/2, H3K4me2/3, and H3K4/9ac) while increased H3K9me3 in mouse testis. Histone H3K9 methylation is linked with gene inhibition, whereas H3K4 methylation and H3K4/9 acetylation contribute to gene activation. ChIP analysis further confirmed that H3K9me2 was markedly decreased in the promoter regions of Cyp11a1 and Hsd17b. Additionally, H3K9me2 demethylase Jhdm2a was significantly increased. These findings suggested that low-level PS-NPs inhibited H3K9me2 through upregulating Jhdm2a, thereby activating key steroidogenic proteins CYP11A1 and 17β-HSD, ultimately promoting testosterone synthesis in mouse testis. Importantly, the changes in testosterone, steroidogenic proteins and histone modifications were effectively reversed upon the cessation of exposure to 500 nm and 100 nm PS-NPs. Collectively, these discoveries offer fresh perspectives on the epigenetic mechanisms underlying male reproductive endocrine disruption caused by PS-NPs, and contribute to assessing the human health hazards associated with exposure to environmental NPs., 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. Published by Elsevier Ltd.)

Neurodegenerative diseases (NDDs) are a group of neurological disorders characterized by the progressive loss of neuronal structure and function, leading to cognitive and behavioral impairments. Despite significant research advancements, there is currently no definitive cure for NDDs. With global aging on the rise, the burden of these diseases is becoming increasingly severe, highlighting the urgency of understanding their pathogenesis and developing effective therapeutic strategies. Microglia, specialized macrophages in the central nervous system, play a dual role in maintaining neural homeostasis. They are involved in clearing cellular debris and apoptotic cells, but in their activated state, they release inflammatory factors that contribute significantly to neuroinflammation. The complement system (CS), a critical component of the innate immune system, assists in clearing damaged cells and proteins. However, excessive or uncontrolled activation of the CS can lead to chronic neuroinflammation, exacerbating neuronal damage. This review aims to explore the roles of microglia and the CS in the progression of NDDs, with a specific focus on the mechanisms through which the CS activates microglia by modulating mitochondrial function. Understanding these interactions may provide insights into potential therapeutic targets for mitigating neuroinflammation and slowing neurodegeneration., Competing Interests: Declaration of Competing Interest The authors declare that this review was conducted in the absence of any commercial or financial supports that could be considered a conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Dexmedetomidine may improve sleep quality after surgery, but conflicting results also exist. Herein, we explored the effects of perioperative dexmedetomidine on postoperative sleep quality in adult patients., Methods: In this systematic review and meta-analysis, randomized controlled trials investigating the effects of perioperative dexmedetomidine on sleep quality after noncardiac surgery were retrieved from Cochrane Library, PubMed, and EMBASE from inception to January 12, 2023, and updated on March 15, 2024. The Cochrane Collaboration's tool was applied to assess risk of bias. A random-effects model was used for meta-analysis. The primary outcome was the subjective sleep quality score on the first night after surgery., Results: A total of 29 trials containing 5610 participants were included. The subjective sleep score on the first postoperative night was lower (better) with dexmedetomidine than with placebo (SMD [standardized mean difference] = -0.8, 95% CI -1.1 to -0.6, p<0.00001; I2 = 93%; 22 trials; n = 4611). Sensitivity analysis showed that overall conclusion was not changed (SMD = -0.8, 95% CI -1.1 to -0.5, p<0.00001; I2 = 93%; 14 trials; n = 3846). Results of polysomnographic monitoring showed improved sleep structure with dexmedetomidine on the first night after surgery, as manifested by increased sleep efficiency index and stage N2 sleep and decreased arousal index and stage N1 sleep., Conclusions: This systematic review suggests that, among patients who underwent noncardiac surgery, perioperative dexmedetomidine administration may improve early postoperative sleep quality pattern. However, the resulting evidence were of low or very low qualities and further studies are required to confirm our results., Prospero Registration Number: CRD42023390972., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Mitochondrial adaptations dynamically reprogram cellular bioenergetics and metabolism and confer key properties for human cancers. However, the selective regulation of these mitochondrial responses remains largely elusive. Here, inspired by a genetic screening in acute myeloid leukemia (AML), we identify RAS effector RREB1 as a translational regulator and uncover a unique translation control system for nuclear-encoded mitochondrial proteins in human cancers. RREB1 deletion reduces mitochondrial activities and succinate metabolism, thereby damaging leukemia stem cell (LSC) function and AML development. Replenishing complex II subunit SDHD rectifies these deficiencies. Notably, inhibition of complex II re-sensitizes AML cells to venetoclax treatment. Mechanistically, a short RREB1 variant binds to a conserved motif in the 3' UTRs and cooperates with elongation factor eEF1A1 to enhance protein translation of nuclear-encoded mitochondrial mRNAs. Overall, our findings reveal a unique translation control mechanism for mitochondrial adaptations in AML pathogenesis and provide a potential strategy for targeting this vulnerability of LSCs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Jiawei-Xiaoyao Pill (JWX), a classic formula in traditional Chinese medicine, is derived from Xiaoyao Pill by adding significant amounts of Gardeniae Fructus (GF) and Moutan Cortex (MC). It is frequently used for the treatment of depression. JWX has been demonstrated to uniquely elicit rapid antidepressant-like effects within the prescribed dosage range. To date, GF has been shown to have rapid antidepressant-like effects, but a much higher dose is required than its proportion in JWX. It is assumed that the synergism of GF with a minimum number of other herbs in JWX serves as a refined formula that exerts these rapid antidepressant-like effects. Identification of a refined formula is important for prioritizing the herbs and ingredients to optimize the quality control of JWX. However, such a refined formula for JWX has not been identified yet., Aim of the Study: Here we aimed to identify a refined formula derived from JWX for optimized rapid antidepressant-like effects. Since the neuroinflammation mechanism involving in depression treatment has not been previously investigated for JWX, we tested the mechanism for both JWX and the refined formula., Materials and Methods: Individual herbs (MC; ASR, Angelica Sinensis Radix; Bupleuri Radix; Paeonia Radix Alba) that show antidepressant-like responses were mixed with GF at the proportional dosage in JWX to identify the refined formula. Rapid antidepressant-like effects were assessed by using NSF (Novelty Suppressed Feeding Test) and other behavioral tests following a single administration. The identified formula was further tested in a lipopolysaccharide (LPS)-induced depressive model, and the molecular signaling mechanisms were investigated using Western blot analysis, immunofluorescence, and pharmacological inhibition of mTOR signaling. Scopolamine (Scop) was used as a positive control for induction of rapid antidepressant effects., Results: A combination of GF, MC and ASR (GMA) at their dosages proportional to JWX induced behavioral signs of rapid antidepressant-like responses in both normal and LPS-treated mice, with the antidepressant-like effects sustained for 5 d. Similar to JWX or Scop, GMA rapidly reduced the neuroinflammation signaling of Iba-1-NF-кB, enhanced neuroplasticity signaling of CaMKII-mTOR-BDNF, and attenuated the upregulated expressions of the NMDAR sub-units GluN1 and GluN2B in the hippocampus of LPS-treated mice. GMA, JWX and Scop rapidly restored the number of BDNF-positive cells reduced by LPS treatment in the CA3 region of the hippocampus. Furthermore, rapamycin, a selective inhibitor of mTOR, blunted the rapid antidepressant-like effects and hippocampal BDNF signaling upregulation by GMA., Conclusion: GMA may serve as a refined formula from JWX, capable of inducing rapid antidepressant-like effects. In the LPS-induced depression model, the effects of GMA were mediated via rapidly alleviating neuroinflammation and enhancing neuroplasticity., Competing Interests: Declaration of competing interest The authors declare there is no commercial or financial relationships that could be construed as a potential conflict of interest regarding this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Interactions of water and chemical or bio-compound have a universal concern and have been extensively studied. For spectroscopic analysis, the complexity and the low resolution of the spectra make it difficult to obtain the spectral features showing the interactions. In this work, the structures and interactions in gaseous water and water-alcohol mixtures were studied using high-resolution infrared (HR-IR) spectroscopy. The spectral features of water clusters of different sizes, including dimer, trimer, tetramer and pentamer, were observed from the measured spectra of the samples in different volume concentrations, and the interactions of water and methanol/ethanol in the mixtures were obtained. In the analysis, a method based on principal component analysis was used to separate the overlapping spectra. In water-alcohol mixtures, when water is less, water molecules tend to interact with the OH groups on the exterior of the alcohol aggregate, and with the increase of water, a water cage forms around the aggregates. Furthermore, the ratio of the molecule number of methanol in the aggregate to that of water in the cage is around 1:2.3, and the ratio for ethanol is about 1:3.2., 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. Published by Elsevier B.V.)

The trigeminal ganglion (TG) comprises primary sensory neurons responsible for orofacial sensations, subsequently projecting to the trigeminal nuclei in the brainstem. However, the circuit basis of nasal mechanosensation is not well characterized. Here we elucidate the anatomical organization of both peripheral and central projections of the TG. We found that the non-peptidergic nociceptor, MrgprD + neurons in the TG densely innervate the nasal mucosa, whereas the LTMRs subtypes rarely innervate the nasal mucosa. We also identified the central projection pattern of the mechanosensory neurons in TG. TrkC + neurons project to dorsal part of the brainstem trigeminal complex and the solitary nucleus. TrkB + neurons project to the Pr5VL, Sp5O, Sp5I and Sp5C. TH + neurons project to ventrolateral Sp5I, the outer edge of Sp5C and the caudal part of solitary nucleus. Additionally, the MrgprD + neurons only densely project to outer edge of Sp5C. In addition, we further determined the ascending pathway of the TG neurons. Taken together, our study demonstrates the peripheral and central projection pattern of mechanosensory neurons in the TG, which provides a basis for the future functional studies., 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. Published by Elsevier Inc.)

Depression is one of the most common mental disorders. Perceived stress is a significant trigger and has adverse effects on depression. The complex longitudinal relationship between perceived stress and depression at the symptom level has significant implications for clinical intervention but is understudied. In our study, 823 students (67% female, median age 20.38, IQR 19.42-21.43) from a university in Tianjin were randomly sampled and completed measures of PHQ-9 and PSS-10, while 393 (65% female, median age 20.42, IQR 19.46-21.45) were followed up at three points, six months apart. The longitudinal relationships were estimated using cross-lagged modelling and cross-lagged panel network modelling. Among them, 49 students (59% female, median age 19.48, IQR 18.76-20.12) participated in resting-state functional magnetic resonance imaging (fMRI) scans. Cross-lagged analyses showed that depression and perceived stress predicted each other at the global level. At the dimensional level, depression and perceived helplessness were mutually predictive, while depression and perceived coping did not. In the cross-lagged panel network analyses, we identified symptoms in the top 20% of Bridge Expected Influence as bridging symptoms, specifically 'Guilt' (PHQ6) and 'Felt nervous and stressed' (PSS3). Notably, 'guilt' consistently demonstrated the highest Bridge Expected Influence across all time points and showed the strongest predictive power for perceived stress. We found that fALFF in the left superior frontal gyrus (SFG) mediated the association between "guilt" and perceived stress. Our findings elucidate the bidirectional relationship between symptoms of depression and perceived stress, identifying guilt is the most critical symptom of depression for the followed perceived stress, with SFG activity mediating this association., (© 2024 John Wiley & Sons Ltd.)

A nanoflower-like MoO 2 -Rh electrocatalyst exhibits a 3.5-fold higher mass activity in the hydrazine oxidation reaction compared with metallic Rh, attributed to the hydrogen spillover, acting as a hydrogen pump to deplete hydrogen from the Rh active site.

Introduction: Placenta accreta spectrum (PAS) disorders pose a grave threat to maternal life due to severe hemorrhage and the heightened risk of peripartum hysterectomy. Consequently, there's a pressing need for circulating biomarkers in clinical settings. MicroRNAs (miRNAs), being stable in peripheral circulation, hold promise as potential biomarkers for PAS., Methods: This study recruited singleton live pregnancies, including cases of invasive PAS, placenta previa (PP), and controls, across three phases. Initially, RNA-seq of peripheral blood identified 6 miRNAs in the screening phase. Subsequently, in the training and validation phases, miR-23a-5p, along with its target genes ASF1B and CHTF8, were validated using qRT-PCR. The diagnostic value of these markers for PAS and adverse outcomes was evaluated using Receiver Operating Characteristic (ROC) curves., Results: The results showed miR-23a-5p was down-regulated in PAS, whereas ASF1B and CHTF8 were up-regulated. miR-23a-5p had modest diagnostic efficiency for PAS and adverse outcomes, as the AUC were 0.689 and 0.711 respectively. However, when miR-23a-5p combined with CHTF8, the AUC can improve greatly to 0.869 in PAS diagnosis and 0.856 in prediction of adverse outcomes., Discussion: We propose the miR-23a-5p plays a role in PAS pathogenesis through regulating cell proliferation, migration, invasion, apoptosis by targeting various genes. This study confirmed its potential value of miR-23a-5p combined with target gene CHTF8 as novel biomarkers for PAS and adverse outcomes., 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. Published by Elsevier Ltd.)

Ongoing soil salinization severely hampers plant growth and the sustainability of global crops production. Hydrogen sulfide (H 2 S), acting as a critical gaseous signaling molecule, plays a vital role in plant response to various environmental cues such as salt stress. Nonetheless, it is not well understood how the transcriptional network regulates H 2 S production in response to salt stress in tomato. Herein, we determine that the bHLH transcription factor SlbHLH92 functions as a transcriptional activator in tomato (Solanum lycopersicum L.), upregulating the expression of the L-CYSTEINE DESULFHYDRASE 1 (SlLCD1) gene involved in H 2 S biosynthesis, thereby enhancing the plants' tolerance to salt stress. When exposed to salt stress, overexpression of SlbHLH92 in tomato leads to enhanced salt tolerance compared to wild-type plants. In contrast, suppression of SlbHLH92 expression with RNAi silencing results in increased sensitivity to salt stress. Subsequent molecular and biochemical investigations confirm that the salt-induced SlbHLH92 upregulates the expression of SlLCD1, leading to an increase in H₂S levels, as well as other salt-responsive genes (SlCBL10 and SlVQ16), by directly binding to specific cis-elements in their promoter regions. Furthermore, the VQ-motif containing protein SlVQ16 physically interacts with SlbHLH92, thereby promoting an increase in its transcriptional activity. Taken together, our study reveals an emerging mechanism in which the SlbHLH92-SlVQ16-H 2 S signaling cascade contributes to enhancing salt tolerance in tomato, presenting potential genetic targets for breeding salt-tolerant tomato cultivars., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Since the snare traction-assisted ESD has been proven effective in treating flat lesions of the digestive tract, we modified and innovated the process and path of the traditional snare entering the digestive tract, aiming to investigate the efficacy and safety of using the per-nasal "GTS partner" assisted traction technology in gastric ESD., Methods: Patients with superficial gastric neoplasms were prospectively enrolled between November 2022 and May 2024 and randomly assigned to a conventional ESD (C-ESD) group or per-nasal "GTS partner" traction-assisted ESD (GTS-ESD) group. The primary outcomes were procedure time and dissection speed., Results: The GTS-ESD and C-ESD groups included 40 patients each, and all the enrolled patients underwent the assigned treatment. The median procedure time in the GTS-ESD group was shorter than that in the C-ESD group (38 min vs. 48 min; P < 0.001), and the mean resection speed of the GTS-ESD group was faster than that of the C-ESD group (17.95 mm 2 /min vs. 11.86 mm 2 /min; P = 0.033). The median resection speed of lesions ≥ 20 mm was faster by GTS-ESD than by C-ESD (21.21 mm 2 /min vs. 12.83 mm 2 /min, P = 0.002). The en bloc resection rate (100% vs 100%) and R0 resection rate (100% vs. 97.5%) were similar between the two groups. There were no adverse events related to the per-nasal "GTS partner" assisted traction technology, and the traction technology had little interference with the endoscopist., Conclusions: The per-nasal "GTS partner" assisted traction technique can significantly shorten the gastric ESD procedure time and has the advantages of no damage to normal mucosa and adjustable traction direction, especially in the lower 1/3 of the stomach or lesions with a diameter of ≥ 20 mm., Competing Interests: Declarations. Disclosures: Yu-Zhen Bi, Li-Min Zhou, Si-Jia Yan, Yan Sun and Jun Zhang have no conflict of interest or financial ties to disclose., (© 2024. The Author(s).)

This narrative review examines the therapeutic efficacy of peripheral nerve stimulation (PNS) in the treatment of neuropathic pain (NP), a type of pain arising from lesions or diseases of the somatosensory system with a global prevalence ranging from 6.90% to 10.00%. Traditional pharmacological interventions often fall short for many persons, highlighting the need for alternative treatments such as PNS, which has demonstrated significant promise with minimal side effects. The review summarizes the effectiveness of PNS in various NP conditions, including trigeminal neuralgia and postherpetic neuralgia, and underscores the need for further research to refine treatment approaches. The mechanism of PNS is discussed, involving the activation of non-nociceptive Aβ fibers and modulation of neurotransmitters, and offering pain relief through both peripheral and central pathways. Despite the proven efficacy of PNS, challenges remain, including the need for randomized controlled trials and the optimization of stimulation parameters. The review concludes that PNS is a promising treatment modality for NP, warranting additional high-quality trials to solidify its role in clinical practice., (© 2024. The Author(s).)

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of childbearing age. The role of Sprouty RTK Signaling Antagonist 4 (SPRY4) in ovarian function in PCOS was investigated herein, focusing on its regulation of ERK1/2 phosphorylation. PCOS models were established in mice using dehydroepiandrosterone (DHEA). The expression levels of SPRY4 in ovarian tissues were analyzed through RT-qPCR and immunohistochemistry. SPRY4 knockdown was achieved via lentivirus, and its effects on endocrine function, ovarian morphology, oxidative stress, and ERK1/2 phosphorylation were evaluated. Afterwards, granulosa cells were isolated and treated with DHEA and ERK2 agonist tert-Butylhydroquinone. The impacts of ERK2 activation on the regulation of SPRY4 knockdown were assessed using ELISA, fluorescent probes, western blotting, and biochemical assays. SPRY4 knockdown normalized the estrous cycle, reduced serum levels of testosterone, anti-Müllerian hormone, and luteinizing hormone/follicle-stimulating hormone ratio, and improved ovarian morphology. Additionally, SPRY4 knockdown alleviated oxidative stress by decreasing reactive oxygen species and malondialdehyde levels while increasing superoxide dismutase activity. It also restored steroidogenic enzyme expression, which were disrupted by DHEA induction. In vitro, SPRY4 knockdown enhanced granulosa cell viability and reduced ERK1/2 phosphorylation, with tert-Butylhydroquinone reversing these effects and restoring oxidative stress and steroidogenesis disruptions. Together, SPRY4 modulates ERK1/2 phosphorylation to influence oxidative stress and steroidogenesis in PCOS. Targeting SPRY4 may provide novel therapeutic avenues for improving ovarian function and managing PCOS., 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.)

Epithelial-mesenchymal transition (EMT) is known to play a crucial role in the development of endometriosis (EMs). However, the exact mechanisms involved in EMT regulation in EMs are not well understood. In this study, we performed comprehensive research using clinical samples, single-cell sequencing, and in vivo/in vitro models to investigate the effects of advanced oxidation protein products (AOPPs) on EMT and the underlying mechanisms in EMs. Combining bioinformatics analysis with experimental validation, our results show that AOPPs accumulate in EMs tissues, and their levels positively correlate with the expression of EMT markers in fibrotic lesions of EMs patients. Stimulation with AOPPs leads to a concentration- and time-dependent alteration of EMT markers expression in both in vitro and in vivo models. These effects are mainly mediated by the generation of reactive oxygen species and nitrite, along with the activation of the ERK and P38 signaling pathways. In chronic administration studies using normal rats, AOPPs induce EMT and enhance collagen deposition. These findings significantly contribute to our understanding of the molecular mechanisms of EMs and provide a foundation for future research and therapeutic development in this field., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This study investigated the protective effect of dapagliflozin on H9c2 cardiomyocyte function under high glucose and hypoxia/reoxygenation (HG-H/R) conditions and identified the underlying molecular mechanisms. Dapagliflozin reduced the level of lactate dehydrogenase and reactive oxygen species in cardiomyocytes under HG-H/R conditions and was accompanied by a decrease in caspase-3/9 activity. In addition, Dapagliflozin significantly reduced mitochondrial permeability transition pore opening and increased ATP content, accompanied by upregulation of OPA1 with autophagy-related protein molecules and activation of the AMPK/mTOR signalling pathway in HG-H/R treated cardiomyocytes. OPA1 knockdown or compound C treatment attenuated the protective effects of dapagliflozin on the cardiomyocytes under HG-H/R conditions. Downregulation of OPA1 expression increased mitochondrial intolerance in cardiomyocytes during HG-H/R injury and the AMPK-mTOR-autophagy signalling is a key mechanism for protecting mitochondrial function and reducing cardiomyocyte apoptosis. Collectively, dapagliflozin exerted protective effects on the cardiomyocytes under HG-H/R conditions. Dapagliflozin attenuated myocardial HG-H/R injury by activating AMPK/mTOR-OPA1-mediated mitochondrial autophagy.

Background: Definitive chemoradiotherapy is recommended as the primary treatment for cervical esophageal carcinoma (CEC). However, local control rates remain unsatisfactory for some patients. Therefore, in this study, we introduced a new treatment paradigm for individuals with CEC, customizing the choice between subsequent local treatments based on their response to induction chemotherapy and immunotherapy., Patients and Methods: Induction treatment comprised two to four cycles of chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitors. Patients achieving complete response (CR) or near CR after induction treatment underwent definitive chemoradiotherapy (dCRT), while those not achieving CR or near CR underwent surgical resection., Results: Among the 40 eligible patients, 14 (35.0%) achieved a CR or near CR after induction treatment. Of the ten patients achieving a CR or near CR, one developed an esophageal fistula after dCRT (10.0%). Among the eight non-CR or non-near CR patients receiving chemoradiotherapy, six developed esophageal fistula (75.0%). Among the 26 patients who did not achieve CR or near CR after induction treatment, the 1-year cancer specific survival (CSS) rates were 93.3% [95% confidence interval (CI) 0.815-1%] for the 18 patients in the surgery group, and 71.4% (95% CI 0.447-1%) for the 8 patients in the chemoradiotherapy group (p = 0.027). The overall laryngeal preservation rate was 85.0% (34/40), with a functional laryngeal preservation rate of 77.5% (31/40)., Conclusion: The approach consisting of combined immunotherapy and chemotherapy successfully identified patients who were responding well to induction treatment and who were sensitive to radiotherapy, for chemoradiotherapy; thus, improving laryngeal preservation rates. In addition, it also identified patients with poor responses to induction treatment and radiotherapy, for timely surgery; hence, reducing radiotherapy complications and enhancing survival., (© 2024. The Author(s).)

Maternal sleep is closely related to subsequent gestational diabetes mellitus (GDM) in natural pregnancies. However, whether this connection exists in pregnant women conceiving with the help of assisted reproductive technology (ART) has not been confirmed. Hence, in this study, we evaluated whether early pregnancy sleep duration or sleep quality is associated with gestational diabetes mellitus in ART-pregnant women, as well as the influence of maternal age on this association. This prospective birth cohort study included 856 pregnant women who successfully conceived with the help of ART treatment. The sleep parameters of ART-pregnant women were assessed using the Pittsburgh Sleep Quality Index (PSQI) in early pregnancy. We explored the association between sleep and the risk of gestational diabetes mellitus using an unconditional binary logistic regression model. Different models were constructed to examine the robustness of the estimation by incorporating different confounding factors. Multivariable logistic regression revealed that sleep duration of more than 10 h among ART-pregnant women was significantly associated with the risk of GDM, and the association between sleep duration and gestational diabetes mellitus varied by maternal age. We found an increased risk of subsequent gestational diabetes mellitus with increasing sleep duration only in pregnant women aged <35 years. Additionally, no statistically significant association between sleep quality and gestational diabetes mellitus was found in this study. In conclusion, excessive sleep duration (≥10 h) is associated with a high risk of gestational diabetes mellitus in pregnant women who conceived with the help of assisted reproductive technology, and maternal age may modify this effect., (© 2024 European Sleep Research Society.)

Background: The species Cupressus funebris holds substantial ecological value and economic potential, particularly in the realms of rehabilitating barren mountain landscapes and advancing urban greening endeavors. However, inadequate attention has been given to research endeavors exploring the genetic diversity and morphological characteristics of Cupressus funebris , a deficiency that could potentially hinder its development, utilization, and conservation of genetic resources., Methods: To rectify the shortage of existing basic morphological data, a morphological analysis was conducted in this study on 180 Cupressus funebris germplasm resources sourced from five provenances. Key traits explored included growth characteristics, overall morphology, branch/leaf features, and seed traits. This will facilitate the evaluation of genetic diversity in Cupressus funebris ., Results: The findings reveal a considerable level of phenotypic variation (PVC of 16.9%) and genetic diversity (1.97 index) in Cupressus funebris germplasm resources. The phenotypic differentiation is observed to be 48% between provenances and 52% within provenances, primarily attributed to variation originating from individual provenances. Based on these morphological characteristics, the germplasm resources have been categorized into four distinct groups: Ecological Restoration Planting, Secondary Reserve Forest, Urban Greening, and Timber Forest. Interestingly, the pattern of variation observed within these groups is irregular, exhibiting no significant correlation with their respective provenances. Furthermore, conifer trees sharing similar growth characteristics tend to display comparable patterns of random variation, suggesting potential underlying genetic mechanisms. This study significantly enriches the phenotypic dataset within the genetic variation research of Cupressus funebris , facilitating development and utilization for ecological construction, timber breeding, and horticultural greening., Competing Interests: The authors declare that they have no competing interests., (© 2024 Yan et al.)

To comprehensively review cardiorenal syndrome (CRS)-related research, this study analyzes its whole landscape and future trends from a bibliometric perspective. Using "cardiorenal syndrome" as the key word, a representative dataset of CRS was constructed in the Web of Science Core Collection (Science Citation Index Expanded) database up to November 2023. VOSviewer (version 1.6.18) and R-Studio (version 1.4) were used to visualize CRS-related author and national collaboration networks, hotspot distribution clustering and historical citation networks. The annual number of publications shows an upward trend, especially since 2009. The United States is the most active country and closely cooperates with European countries. Cardiorenal Medicine is the journal that publishes the most CRS-related research. Urology & Nephrology and Cardiovascular System & Cardiology are the most prominent areas of CRS literature output. The leaders in CRS-related research are Ronco C from Italy and Mccullough PA, from the United States. Combined with keyword co-occurrence, theme evolution, and strategic distribution analysis, it was found that centering on the mechanism of CRS (cardiovascular lesions, venous congestion, and fibrosis), prognosis (transplantation, dialysis, hospitalization, mortality) and cardiac function management (b-type natriuretic peptide, diastolic dysfunction, left ventricular hypertrophy) is a possible research direction for a long time to come. Although CRS has a relatively short history, it has received a lot of attention and is currently enjoying a high level of overall acceptance. In conclusion, this study explores the major research areas, frontiers and trends in CRS, which are important for future research., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Despite advancements in breast cancer treatment, therapeutic resistance, and tumor recurrence continue to pose formidable challenges. Therefore, a deep knowledge of the intricate interplay between the tumor and the immune system is necessary. In the pursuit of combating breast cancer, the awakening of antitumor immunity has been proposed as a compelling avenue. Tumor stroma in breast cancers contains multiple stromal and immune cells that impact the resistance to therapy and also the expansion of malignant cells. Activating or repressing these stromal and immune cells, as well as their secretions can be proposed for exhausting resistance mechanisms and repressing tumor growth. NK cells and T lymphocytes are the prominent components of breast tumor immunity that can be triggered by adjuvants for eradicating malignant cells. However, stromal cells like endothelial and fibroblast cells, as well as some immune suppressive cells, consisting of premature myeloid cells, and some subsets of macrophages and CD4+ T lymphocytes, can dampen antitumor immunity in favor of breast tumor growth and therapy resistance. This review article aims to research the prospect of harnessing the power of drugs, adjuvants, and nanoparticles in awakening the immune reactions against breast malignant cells. By investigating the immunomodulatory properties of pharmacological agents and the synergistic effects of adjuvants, this review seeks to uncover the mechanisms through which antitumor immunity can be triggered. Moreover, the current review delineates the challenges and opportunities in the translational journey from bench to bedside.

Inflammatory bowel disease refers to a group of non-specific inflammatory illnesses affecting the gastrointestinal tract. According to pathogenic characteristics, it is divided into Ulcerative colitis and Crohn's disease. The exact cause and pathogenic mechanism of these disorders are not yet fully understood. In addition, there is currently no definitive diagnostic method for inflammatory bowel disease, which mainly depends on clinical symptoms, blood testing, imaging investigations, and endoscopic examination, which includes histology. Endoscopic Ultrasonography is a digestive tract examination technique that combines endoscopy and ultrasound. Compared to conventional endoscopy, it can visualize surface and deep lesions of the gastrointestinal wall, as well as provide information on the characteristics of the surrounding layers and nearby lymph nodes. Due to these advantages, Endoscopic Ultrasonography has played a significant role in the evaluation of inflammatory bowel disease in recent years. Through this work, we aim to identify the applications of this method in the case of patients with inflammatory bowel disease., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interests for this article., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The efficiency of molecular breeding largely depends on the cost of genotyping, which plays an important role in breeding and population genetic studies. Compared to pig, cattle, and sheep, poultry has a small size genome, and lower individual value. Developing a relatively low-density genotyping panel is needed to decrease the genotyping cost for poultries. In the present study, we developed a chicken 11 K single nucleotide polymorphism (SNP) genotyping panel for breeding and genetic analysis using genotyping by targeted sequencing (GBTS). The panel design was based on whole genome sequencing data from 7 local breeds and a commercial breed. In total 11,200 SNPs were included in the final chip. Population analyses of the eight breeds showed high SNP call rates and minor allele frequencies (MAF), enabling clear differentiation between populations. The families within population can also be identified. Additionally, the 11K panel was applied to a genomic prediction of Wenshang Barred chickens, the predictive ability and prediction accuracy between the WGS and chip dataset non-significantly differed. Therefore, the newly developed chicken low-density SNP is efficient, cost-effective, and well-suited for application in local Chinese chickens, which can accelerate chicken breeding improvements and enhance conservation efforts., 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. Published by Elsevier Inc.)

Nucleolar protein 3 (NOL3), as a markedly increased protein across a range of tumors, has been well acknowledged that plays an anti-apoptotic role in malignancies, while some novel impacts of NOL3 on metastasis and chemoresistance are demonstrated recently. In this study, we uncover another role of NOL3 on promoting proliferation in bladder cancer (BLCA). The reduction of NOL3 significantly inhibited cell proliferation, and we detected the stable cell cycle arrest after knockdown of NOL3 in two-type BLCA cell lines. Mechanistically, we present the first evidence that the PI3K/Akt pathway was considerably inhibited with the decrease of NOL3 in BLCA cell lines. In addition, LY294002, a PI3K inhibitor, rescued NOL3 overexpression-mediated activation of the PI3K/Akt axis and the depression of proliferation in BLCA cell lines. In conclusion, our study suggests that NOL3 is upregulated in BLCA cells and promotes proliferation via the PI3K/Akt pathway, indicating that NOL3 may be a potential therapeutic target for BLCA., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Institutional Review Board Statement: The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board (or Ethics Committee) of The First Affiliated Hospital of Chongqing Medical University (protocol code 2021-085 and 3 March 2021 of approval) for studies involving humans. The animal study protocol was approved by the Institutional Animal Care and Use Committee (IACUC) of Chongqing Medical University (IACUC-CQMU-2023-0226). Informed consent: Informed consent was obtained from all subjects involved in the study., (© 2024. The Author(s).)

Purpose: To evaluate the availability of human resources for ophthalmic services in mainland China., Methods: In 2021, we conducted a nationwide survey of ophthalmic outpatient services across 2996 tertiary hospitals and 10,404 secondary hospitals in 31 provinces in mainland China., Results: The response rate was 73.6% (9856/13400), with 78.7% (7759/9856) providing ophthalmic services. By 2021, the total number of ophthalmologists, ophthalmic nurses, and optometrists was 48,652, 64,495, and 14,320, respectively. The densities (per 50,000 population) were 1.7, 2.25, and 0.47, respectively. The density of ophthalmologists was < 1 only in the XiZang region. The average doctor-patient ratio was 2584.8. In Shanghai and Zhejiang provinces, this ratio exceeded 4000., Conclusion: There are currently 1.7 ophthalmologists, 2.25 nurses, and 0.47 optometrists for every 50,000 people in China. The number of ophthalmologists has reached the global average, but the number of optometrists is far below the global average. And the medical pressure across China is uneven, with some provinces such as Shanghai and Zhejiang facing enormous pressure., Competing Interests: Declarations. Ethics approval and consent to participate: This study does not involve specific patients or participants, informed consent was deemed unnecessary by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University. The Ethics Committee of Beijing Tongren Hospital approved this study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The anterior cingulate cortex (ACC) of the human brain is involved in higher-level cognitive functions such as emotion and self-awareness. We generated profiles of human and macaque ACC gene expression and chromatin accessibility at single-nucleus resolution. We characterized the conserved patterns of gene expression, chromatin accessibility, and transcription factor binding in different cell types. Combining the published mouse data, we discovered the molecular identities and cell-lineage origin of the primate von Economo neurons (VENs). Our in vitro and in vivo experiments identified a group of primate-shared and human-specific VEN marker genes, such as PCSK6, ADAMTSL3, and CDHR3, potentially contributing to VEN morphogenesis. We demonstrated that the human-specific sequence changes account for the cellular and functional innovations in the ACC during primate evolution and human origin. These findings provide new insights into understanding the cellular composition and molecular regulation of ACC and its evolutionary role in shaping human-owned higher cognitive skills., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Five new coumarins, including three phenypropaninized coumarins edgegardnerols A-C (1-3), two bicoumarins edgegardnerols D and E (4 and 5), along with eight known analogues, were isolated and identified from the dried buds of E. gardneri. Their structures were elucidated by comprehensive analysis of their NMR, IR, UV, HR-ESI-MS, and ECD data. Furthermore, the absolute configurations of the glucose moiety were confirmed by HPLC analysis after acidic hydrolysis and chemical derivatization. The cytotoxic activities of all isolated compounds were evaluated against A549 and SMMC-7721 cell lines. Among the tested isolates, compound 12 showed the most potent cytotoxicity with IC 50 values of 22.65 μM and 25.83 μM in these two cell lines, respectively. Compared with cisplatin (29.78 μM), compound 12 exhibited stronger cytotoxic activity in A549 cell line. The preliminary structure-activity relationship showed that 7-hydroxy group on coumarin skeleton was structurally required for the cytotoxity against the A-549 and SMMC-7721 cell lines., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To investigate the associations between comorbidities and multimorbidity patterns with motor and neuropsychiatric symptoms in patients with Parkinson's disease (PD) in prodromal PD., Methods: Multimorbidity is defined as the coexistence of two or more long-term conditions (LTCs) (also known as multiple comorbidities). A total of 921 participants without PD were included in the Parkinson's Progression Markers Initiative (PPMI) database and were categorized according to the LTC count. Participants were evaluated on motor and psychiatric symptoms. Pearson correlation to examine relationship of comorbidities and target symptoms. The baseline population was analyzed using Multiple linear regression model, while mixed effects model was utilized for longitudinal analysis. Fuzzy C-means clustering analysis was conducted to identify comorbidity patterns, followed by multiple linear regression for further analysis., Results: At baseline, a higher LTC count was significantly correlated with more severe motor (MDS-UPDRS I, II, ADL, all P < 0.05) and neuropsychiatric symptoms (QUIP, P < 0.001). Three multimorbidity patterns were identified. Among them, the cardiometabolic multimorbidity pattern (CAR) had the most significant correlation with the aforementioned symptoms. Our longitudinal analysis indicated that an increase in the LTC count was associated with the exacerbation of motor and neuropsychiatric symptoms., Conclusion: Comorbidities were cross-sectionally and longitudinally associated with the motor and neuropsychiatric symptoms of patients with prodromal PD. Among the three multimorbidity patterns, CAR posed the highest threat to the risk of more severe motor and neuropsychiatric symptoms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Sun, Ma and Tan.)

The aim of this study was to investigate the genetic factors of a patient with germinal vesicle arrest in oocytes. Clinical data and blood samples were collected from the patient and some were amplified for high-throughput gene and Sanger sequencing. Several molecular and cellular experiments were performed to determine the association between the gene mutation and germinal vesicle arrest. Two mutation sites (c.1282G > T and c.1247C > A) were found in the PATL2 gene. The c.1282G > T mutation is associated with oocyte maturation abnormalities according to previous research, whereas c.1247C > A is a novel mutation of unknown clinical significance. In cell transfection experiments, qRT-PCR, immunofluorescence, and Western blotting revealed that the mRNA and protein levels of the PATL2 gene with the c.1247C > A mutation were reduced. Sanger sequencing suggested that the patient inherited the PATL2 mutations from her parents via a compound heterozygous mode of inheritance. Collectively, this study describes the PATL2 -gene c.1247C > A mutation associated with germinal vesicle arrest in oocytes, providing a useful target for genetic and background tests for patients presenting with oocyte maturation abnormalities and/or germinal vesicle arrest following multiple unsuccessful attempts with assisted reproductive technology., 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.)

Sulfate-reducing bacteria (SRBs) and dissimilatory iron-reducing bacteria (DIRBs) are recognized as significant contributors to the occurrence of elevated arsenic (As) levels in groundwater. However, the precise effects and underlying mechanisms of their interactions on As behavior within sediments remain poorly understood. In this investigation, we compared the impacts and mechanisms of DIRBs, SRBs, and mixed bacterial consortia on the migration behavior of As and Fe/S species. Our findings revealed that during the initial phase of the reaction (0-8 days, Stage 1), the mixed bacterial consortium facilitated As release by intensifying the reduction of Fe (III) and sulfate, resulting in a maximum As concentration 1.5 times higher than that observed with either DIRBs or SRBs in isolation. Subsequently, in the intermediate phase (8-20 days, Stage 2), the mixed consortium suppressed the synthesis of sulfate reductase and the secretion of toxic substances (e.g., o-Methyltoluene) associated with steroid degradation pathways. This inhibition consequently reduced the formation of secondary Fe minerals and the fixation of As. Finally, in the latter stage (20-30 days, Stage 3), the system responded to the threat of toxic substances by secreting significant amounts of organic acids to facilitate their decomposition. However, this process also led to the re-decomposition of iron oxides, resulting in the release of As. These observations shed light on the intricate interplay between DIRBs and SRBs within bacterial consortia, elucidating their coordinated actions in inducing the migration and transformation of arsenic., 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. Published by Elsevier Ltd.)

Objective: This study aims to explore the effect of a case management model that breaks through the temporal and spatial characteristics on the at-home phase II exercise rehabilitation of postoperative patients treated with percutaneous coronary intervention (PCI)., Methods: We used the convenience sampling method to select 103 patients with coronary artery disease (53 in the observation group and 50 in the control group) who were admitted to the Department of Cardiovascular Internal Medicine at the Jiaxing No. 2 Hospital in January 2022 and January 2023 and underwent PCI treatment as study subjects. Patients in the control group were managed by the conventional continuity of care model, and those in the observation group were managed by the case management model that breaks through the temporal and spatial characteristics. Both groups of patients were intervened and followed up for 6 months, comparing the adherence to home II exercise rehabilitation and regular follow-ups, coronary heart disease risk factor indexes, unplanned readmission rate, and the incidence of adverse cardiovascular events between the two groups of patients., Results: Exercise adherence and regular follow-up adherence of patients discharged from the hospital at 1, 3, and 6 months after PCI were higher in the observation group than in the control group ( P  < 0.05). The comparison of risk factor indicators of patients in both groups at 6 months after discharge with those of patients before discharge showed different degrees of improvement, and the difference was statistically significant ( P  < 0.05). However, the difference in fasting blood glucose in the control group at 6 months after discharge compared with that before discharge was statistically significant ( P  < 0.05), whereas there was no statistical significance in the observation group ( P  > 0.05). The incidence of major adverse cardiovascular events and unplanned readmission at 6 months after discharge between the two groups was lower in the observation group than in the control group, and the difference was statistically significant ( P  < 0.05)., Conclusion: The case management mode that breaks through the spatiotemporal characteristics can improve the exercise adherence and regular follow-up adherence of post-PCI patients' at-home phase II exercise rehabilitation, which can effectively control the indexes of body mass index (BMI), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) and reduce the rate of unplanned readmission and the incidence of adverse cardiovascular events., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Jin, Wu, Huang, Zheng, Sun, Lu, Meng and Yu.)

Objectives: To develop methods for early detection of natural killer/T-cell lymphoma, nasal type (nasal NKTL) and to evaluate the use of apparent diffusion coefficient (ADC) measurements from diffusion-weighted imaging (DWI) for selecting biopsy sites to enhance the positive biopsy rate., Methods: The clinical data of 32 cases of nasal NKTL were retrospectively collected and analyzed. Cases were graded from 1 to 5 based on endoscopic and imaging findings. Biopsy methods included the superficial forceps method and deep incisional method. Data recorded included biopsy method, time to confirmed diagnosis, number of biopsies required, and ADC values of biopsy sites., Results: Both endoscopic and MRI lesion severity did not affect biopsy outcomes (p = 0.8248, 0.7571). The deep incisional biopsy method had a significantly higher probability of yielding positive pathological results compared to the superficial clamping method [OR (95% CI) = 23.2143 (6.0448, 89.1513) (χ 2  = 26.1089, p < 0.0001)]. The ADC value at the site with a positive biopsy result is significantly lower than at the site with a negative result (p = 0.0003). The diagnostic threshold for ADC value to predict a positive biopsy result was 0.603 × 10 -3  mm 2 /s, with a Youden index of 0.43., Conclusions: Nasal NKTL has distinct characteristics distinguishing it from sinusitis and other tumors. Deep incision biopsy under general anesthesia is superior to the superficial method. The location of the positive sampling site can be guided by measuring the ADC value, and the optimal diagnostic threshold of this proposed method is 0.603 × 10 -3  mm 2 /s., Level of Evidence: 4 Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Abstract: The European LeukemiaNet (ELN) acute myeloid leukemia (AML) genetic risk classification systems are based on response to intensive chemotherapy; their ability to discriminate outcomes in older patients treated with venetoclax-azacitidine may be suboptimal. This pooled analysis of the phase 3 VIALE-A trial (NCT02993523) and phase 1b study (NCT02203773) examined prognostic stratification according to the 2017 and 2022 ELN risk classifications and derived new molecular signatures differentiating venetoclax-azacitidine-treated patients based on overall survival (OS). Overall, 279 patients treated with venetoclax-azacitidine and 113 patients treated with placebo-azacitidine were analyzed. The ELN 2017 or 2022 prognostic criteria classified most patients as adverse-risk AML (60.2% and 72.8% for venetoclax-azacitidine and 65.5% and 75.2% for placebo-azacitidine, respectively). Although outcomes with venetoclax-azacitidine improved across all ELN risk groups compared with placebo-azacitidine, ELN classification systems poorly discriminated venetoclax-azacitidine outcomes. By applying a bioinformatic algorithm, new molecular signatures were derived differentiating OS outcomes with venetoclax-azacitidine. The mutational status of TP53, FLT3 internal tandem duplication (FLT3-ITD), NRAS, and KRAS categorized patients into higher-, intermediate-, and lower-benefit groups (52%, 25%, and 23% of patients, respectively), each associated with a distinct median OS (26.5 months [95% confidence interval (CI), 20.2-32.7]; 12.1 months [95% CI, 7.3-15.2]; and 5.5 months [95% CI, 2.8-7.6], respectively). ELN prognostic classifiers did not provide clinically meaningful risk stratification of OS outcomes in patients treated with venetoclax-azacitidine. TP53, FLT3-ITD, NRAS, and KRAS mutation status allows the classification of these patients into 3 risk groups with distinct differences in median OS. These trials were registered at www.clinicaltrials.gov as #NCT02993523 and #NCT02203773., (© 2024 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: The early childhood period is a critical development stage, and experiencing stress during this time may increase the risk of gastrointestinal disorders, including irritable bowel syndrome (IBS). Neonatal maternal separation (NMS) in rodent models has been shown to cause bowel dysfunctions similar to IBS, and 5-HT is considered to be a key regulator regulating intestinal function, but the precise underlying mechanisms remain unclear., Results: We established a maternal separation stress mouse model to simulate early-life stress, exploring the expression patterns of 5-HT under chronic stress and its mechanisms affecting gut function. We observed a significant increase in 5-HT expression due to NMS, leading to disruptions in intestinal structure and function. However, inhibiting 5-HT reversed these effects, suggesting its potential as a therapeutic target. Furthermore, our research revealed that excess 5-HT in mice with early life stress increased intestinal neural network density and promoted excitatory motor neuron expression. Mechanistically, 5-HT activated the Wnt signaling pathway through the 5-HT 4 receptor, promoting neurogenesis within the intestinal nervous system., Conclusion: These findings shed light on the intricate changes induced by early life stress in the intestines, confirming the regulatory role of 5-HT in the enteric nervous system and providing potential insights for the development of novel therapies for gastrointestinal disorders., Competing Interests: The authors declare that they have no competing interests., (© 2024 Yang et al.)

In this research, β-cyclodextrin magnetic-graphene-oxide pyrenyl gel composite (β-mGOP) was employed to remove trace mycotoxins from food products. The β-mGOP gels exhibited a three-dimensional macroporous structure that facilitated the rapid diffusion of target molecules into the nanoporous structure of the covalent organic frameworks embedded within the gel. The adsorption process of mycotoxins onto the β-mGOP gels conformed to the pseudo-second-order kinetics and the Freundlich adsorption model. These findings demonstrated exceptional rapid adsorption kinetics without pore collapse, making the material suitable as fillers for solid-phase extraction adsorbents. Additionally, a novel screening technique utilizing β-mGOP gels in conjunction with cyclic ion mobility mass spectrometry was developed to illustrate the efficacy of β-mGOP gels in capturing various trace substances in food and enhancing detection resolution. The versatile, uncomplicated, and scalable characteristics of β-mGOP gels indicate their promising potential for future applications in high-throughput analysis of trace contaminants in food., 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.)

Background: The interactions between pollutants and temperature coexposure, the mixing effects and their potential mechanisms remain uncertain., Methods: This retrospective cohort study included 11,766 women with infertility who received treatment at Fujian Hospital between 2015 and 2024. The daily mean concentrations of the six pollutants and the relative humidity and temperature data were acquired from the Fujian region. Data on genes were obtained from the Comparative Toxicogenomics Database., Results: O 3 (aOR=0.80, 95 % CI=0.725--0.891) and temperature (aOR=0.936, 95 % CI=0.916--0.957) were negatively correlated with live birth rates. Moreover, PM 10 (aOR=1.135, 95 % CI=1.028--1.252) and PM 2.5 (aOR=1.146, 95 % CI=1.03--1.274) were positively associated with preterm birth. Among the effects on live births, PM 2.5 , PM 10 , NO 2 , CO, and SO 2 had significant synergistic effects with temperature; in addition, O 3 had significant antagonistic effects with temperature. A notable trend toward declining live birth rates with elevated concentrations of mixed pollutants was observed. Different infertility patients have different sensitivities to coexposure. Gene enrichment and cell experiments are associated mainly with cellular life activities., Conclusions: Individual effects, interactions, and mixed effects between temperature and air pollutants and birth outcomes persist when air pollutant levels are relatively low. AAP may trigger miscarriage through cytotoxic effects., 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.)

Precision medicine is the future of drug development, and subgroup identification plays a critical role in achieving the goal. In this paper, we propose a powerful end-to-end solution squant (available on CRAN) that explores a sequence of quantitative objectives. The method converts the original study to an artificial 1:1 randomized trial, and features a flexible objective function, a stable signature with good interpretability, and an embedded false discovery rate (FDR) control. We demonstrate its performance through simulation and provide a real data example., (© 2024 John Wiley & Sons Ltd.)

Introduction: Age-related hearing loss (ARHL) is a degenerative condition that involves both peripheral and central auditory system pathologies. There is a close relationship between chronic inflammation and ARHL, but there is currently a lack of in-depth exploration of this relationship, particularly regarding causality., Methods: Using age-appropriate mice for basic experiments to examine changes in central auditory nervous system inflammation, a cohort study was conducted to select relevant clinical data and observe inflammation changes in the elderly population with ARHL. Mendelian randomization was employed to investigate the causal relationship between chronic inflammation and ARHL., Results: Clinical results indicate that CRP levels in the ARHL group are significantly higher than those in the normal group. Chronic inflammation also occurs in the auditory centers. Mendelian randomization studies provide causal evidence that genetic chronic inflammation factors do not increase the risk of ARHL., Discussion: This article provides reliable causal evidence of the relationship between chronic inflammation and ARHL, confirming the accumulation of inflammatory factors in the auditory center, which provides a basis for the prevention and treatment of ARHL and has a good prevention prospect. However, due to the differences of research objects, this study has limitations and needs further research., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Wang et al.)

All-fiber continuous-wave (CW) and passively Q-switched lasers at 1.36 µm ( 4 F 3/2  →  4 I 13/2 ) by a Nd 3+ -doped double cladding phosphate fiber are demonstrated for the first time, to the best of our knowledge. To suppress the competitive 0.9 and 1.05 µm emission, the Yb 3+ ions are intentionally introduced into the inner cladding of this Nd 3+ -doped fiber. CW laser at 1.36 µm with a signal-to-noise ratio over 50 dB is realized by using two fiber-type dielectric films as cavity mirrors. A 4.0% CW laser efficiency is obtained when the Nd 3+ -doped fiber length is 33 mm. The emission at 0.9 and 1.05 µm is well-suppressed, and no parasitic laser is observed. Taking a commercial semiconductor saturable absorber (SA) mirror as the SA, the compact 1.36-µm Q-switched laser is demonstrated, and the repetition rate of output pulses can be tuned from 230 to 522 kHz with a narrowest pulse duration of 152 ns. Our results may provide a promising way to realize 1.3 µm laser oscillation in Nd 3+ -doped fibers.

Aims: Clinical data supports electroacupuncture (EA) as an effective treatment for female reproductive disorders especially gonadotropin abnormalities. This study aims to detect the mechanism of EA that improves the neuroendocrine defects particularly the luteinizing hormone (LH) surge failure in early reproductive aging females., Materials and Methods: Middle-aged ovariectomized rats primed with hormone were treated by EA at acupoints CV4 and SP6 and undergone LH assay. Morphological experiments detected the activation of Kiss1 cells in the anteroventral periventricular nucleus (AVPV). Using targeted liquid chromatography with tandem mass spectrometry (LC-MS/MS) and RNA-sequencing, we determined the concentrations of neurotransmitter metabolites and transcriptomics in AVPV., Key Findings: EA significantly increased c-Fos and c-Fos-positive Kiss1 cells in the middle-aged AVPV as well as the total and peak LH release. Targeted LC-MS/MS and RNA-sequencing of AVPV identified differential neurotransmitters in the middle-aged females including Acetylcholine chloride, 5-Hydroxyindole-3-aceticacid, Kynurenine, Histamine, L-Histidine and L-Glycine, while EA decreased the concentration of Acetylcholine chloride. Totally 1255 differentially expressed genes modulated by EA were strongly implicated in neurotransmitter transport and KEGG pathways involved neuroactive ligand-receptor interaction, glutamatergic and gamma-aminobutyric acid-mediated synapse. Specifically, the mRNAs associated with the LH surge such as hormone receptor Pgr, adrenoceptor Adra1a, neurotransmitter transporters Slc17a6 and Slc32a1, glutamate decarboxylase Gad2 and Kiss1 were markedly altered by EA., Significance: These findings showed that the age-related reduction of LH surge occurred via differential neurotransmitter metabolisms and altered transcriptions in AVPV, which proposed EA-based therapy for improving responsiveness of the hypothalamus to hormone in women with advanced age., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Research on the associations of type-specific bullying victimization and poly-bullying victimization with suicidal ideation is limited and contradictory. This study aimed to examine these associations among school-aged adolescents., Methods: A total of 13,258 students from 3 middle schools and 4 high schools in a southern city in China completed a cross-sectional questionnaire in 2019. Multinomial logistic regressions were used to examine associations between type-specific bullying victimization and poly-victimization with suicidal ideation., Results: The latent class analysis identified three subgroups of suicidal ideation: low (70.0 %), moderate (24.0 %), and high (6.0 %). Compared with non-bullying victimization in the past year, the corresponding adjusted odds ratios [aOR] (95 % CI) of moderate and high suicidal ideation for only physical victimization were 1.74 (1.15, 2.63) and 2.51 (1.18, 5.38), respectively, for only relational victimization were 1.26 (0.97, 1.62) and 2.48 (1.65, 3.71), respectively, for only verbal victimization were 1.45 (1.17, 1.78) and 1.42 (0.90, 2.22), respectively, for only property victimization were 1.30 (1.03, 1.65) and 1.31 (0.80, 2.16), respectively, and for sexual victimization were 1.38 (1.03, 1.83) and 2.45 (1.50, 3.99), respectively. Poly-bullying victimization was associated with moderate (aOR two  = 1.45 (1.24, 1.70); aOR three  = 1.70 (1.41, 2.05), aOR four  = 2.03 (1.61, 2.58), aOR five  = 2.48 (1.74, 3.53)) and high suicidal ideation (aOR two  = 2.01 (1.49, 2.70), aOR three  = 3.87 (2.86, 5.25), aOR four  = 4.55 (3.20,6.46), aOR five  = 7.90 (5.06, 12.33))., Limitations: The research design is cross-sectional, and relevant data was based on self-reports., Conclusions: Different types of bullying victimization were associated with suicidal ideation and poly-bullying victimization and suicidal ideation association shows a dose-response-relationship., Competing Interests: Declaration of competing interest None of the authors have declared any potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: FGFR2 fusion has become a promising therapeutic target in iCCAs; however, the procedure for screening FGFR2 fusion has not been conventionally developed., Methods: FGFR2 fusion was identified using DNA + RNA-based NGS and FISH, and the concordance between DNA + RNA-based NGS, FISH, and IHC was compared., Results: FGFR2 fusions were detected in 9 out of 76 iCCAs (11.8%). The consistency of FISH and DNA + RNA-based NGS for FGFR2 fusions was high (κ value = 0.867, P = 0.001), while the consistency of IHC and DNA + RNA-based NGS was lower (κ value = 0.464, P = 0.072). All nine FGFR2 fusion-positive iCCAs were MSS with a median TMB of 2.1 mut/Mb, and only one had a CPS (PD-L1) above 5. Two FGFR2 fusion-positive iCCA patients were treated with and benefited from FGFR inhibitor therapy., Conclusions: FGFR2 fusion should be assessed for advanced iCCA patients. We recommend DNA + RNA-based NGS as the preferred option to supply all possible therapeutic targets. FISH should be preferred if the tumor sample is insufficient for NGS or if the patient is inclined to receive FGFR inhibitors promptly. Although IHC is not the preferred method to identify FGFR2 fusion, it might be used as preliminary screening for FGFR2 alterations if the hospital cannot offer NGS or FISH, and the results need to be validated before FGFR2 inhibitors treatment., Competing Interests: Declarations Conflict of interest The authors declare that they have no conflict of interest. Ethical approval This study was approved by the Institutional Review Board of TMUCIH (bc20240020) in compliance with the Helsinki Declaration. Written informed consent was obtained from individual or guardian participants., (© 2024. Japanese Society of Gastroenterology.)

Objective: This study was aimed to analyze the clinical and genetic characteristics of hypoparathyroidism in children., Methods: We performed a retrospective analysis of 74 patients diagnosed with pediatric hypoparathyroidism from 2014 to 2023, recruited in five medical centers across China. Data of basic information and clinical tests were extracted from patients' records. Whole-exome sequencing (WES), multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray analysis (CMA) were utilized to identify the genetic causes., Results: The results indicated a median onset age of 6.07 ± 4.82 years and a median diagnosis age of 6.91 ± 4.88 years. Of the 46 patients who underwent genetic tests, 35 were found to carry pathogenic variants related to hypoparathyroidism. Specifically, 19 cases (19/46, 41.30%) had 22q11.2 microdeletion, while other variations included AIRE (8/46, 17.39%), GATA3 (3/46, 6.52%), CaSR (2/46, 4.34%), and the rest 3 patients with mutations of TBCE, PTH and mitochondrial gene deletion respectively. Convulsions were the most common initial presentation, observed in 43 cases. The non-DGS group exhibited the lowest serum PTH levels compared to DiGeorge syndrome and gene-negative group. Among the 66 patients who underwent cranial CT or MR, 26 (26/66, 39.99%) presented with intracranial calcification., Conclusions: We reported the largest cohort of childhood hypoparathyroidism with genetic diagnoses, reinforcing the view that genetic disorders account for the majority of pediatric hypoparathyroidism, with the 22q11.2 microdeletion being the most prevalent. Identifying the genetic causes of hypoparathyroidism is crucial for predicting patient outcomes, managing comorbidities, and, importantly, informing decisions regarding the potential use of emerging recombinant human PTH therapy., Competing Interests: Declarations Competing interests There are no conflicts of interest to disclose., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)