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Texture is an important quality index reflecting a series of sensory evaluations of fruit, and softening is the main texture change of most postharvest fruit. Persimmon fruit ( Diospyros kaki ) shows a pattern of decreasing firmness after harvest, leading to a short duration of sale and excessive waste. We found that the treatment with gibberellin (GA) could effectively inhibit the postharvest softening of persimmon fruit, but the underlying mechanism is unclear. In the GA signal transduction pathway, DELLA protein is the key component and is involved in many growth and development processes regulated by GA, while whether DELLA is involved in GA-regulated fruit ripening is not yet known. In this research, two DELLA genes DkDELLA1/2 were found to enhance the transactivation effect of DkNAC9 on the DkEGase1 promoter, thus participating in persimmon fruit softening regulated by GA. The results may provide new findings for the regulatory network of GA and the DELLA protein family.

Abstract: This study aimed to introduce a modified Byars staged procedure and investigate its application value in patients with severe hypospadias. We retrospectively analyzed the clinical data of patients with severe hypospadias admitted to the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between October 2012 and October 2022. In total, 31 patients underwent the conventional Byars procedure (conventional group), and 45 patients underwent the modified Byars staged procedure (modified group). Our modified strategy was built upon the standard Byars procedure by incorporating glansplasty during the first stage and employing a Y-shaped flap in conjunction with a glandular tunnel for urethroplasty during the second stage. Notably, there were no statistically significant differences in the preoperative baseline characteristics, duration of surgery, amount of blood loss, or occurrence of postoperative complications, including urethral fistula, stricture and diverticulum, or penile curvature, between the conventional and modified groups. However, there was a significantly lower incidence of coronal sulcus fistula (0 vs 16.1%, P = 0.02) and glans dehiscence (0 vs 12.9%, P = 0.02) in the surgical group than that in the conventional group. In addition, the modified group exhibited a notably greater rate of normotopic urethral opening (100.0% vs 83.9%, P = 0.01) and a higher mean score on the Hypospadias Objective Penile Evaluation (HOPE; mean ± standard error of mean: 8.6 ± 0.2 vs 7.9 ± 0.3, P = 0.02) than did the conventional group. In conclusion, the modified Byars staged procedure significantly reduced the risks of glans dehiscence and coronal sulcus fistula. Consequently, it offers a promising approach for achieving favorable penile esthetics, thereby providing a reliable therapeutic option for severe hypospadias., (Copyright ©The Author(s)(2024).)

Aim: We explored demoralisation syndrome among post-operative patients with breast cancer and its relationship with patients' body image and marital intimacy., Design: A cross-sectional study., Methods: In this cross-sectional study, 237 patients with breast cancer who were hospitalised in the breast surgery department of Grade A tertiary hospital in Xiamen, China from June 2022 to December 2023 and met the standards of adaxation were selected by the convenience sampling method. The survey tool consists of four parts: general data questionnaire, demoralisation scale-II (DS-II), quality of relationship index (QRI) and body image scale (BIS)., Results: In this study, we examined the demoralisation syndrome in 237 post-operative breast cancer patients, predominantly aged 45-59 years (47.3%), with the majority living with family (94.1%) and having children (95.4%). A small proportion (5.9%) lived alone, and 3% were uninsured, opting to pay for their treatment out-of-pocket. The majority (83.1%) had undergone mastectomy, and 51.9% visited the hospital for chemotherapy, with 5.1% experiencing disease recurrence. The mean demoralisation score was 8.52 (SD = 8.47). We found that 22.8% had moderate and 14.8% had severe demoralisation symptoms. Socioeconomic factors such as age, residence, income, tumour staging, post-operative time, hospital purpose and disease recurrence were associated with demoralisation. Multivariate analysis revealed that income, cancer stage, recurrence, quality of recovery index (QRI) and BIS were independent influencing factors for demoralisation syndrome after breast cancer surgery. These findings highlight the importance of considering a range of patient characteristics when addressing demoralisation in post-operative breast cancer patients., Patient Contribution: Demoralisation syndrome in patients after breast cancer surgery is influenced by a combination of sociodemographics, disease, intimate relationship and body image. Clinical medical staff should accurately evaluate and identify patients with demoralisation syndrome after breast cancer surgery and formulate and implement personalised intervention strategies according to their physical conditions and possible influencing factors, so as to reduce the incidence of demoralisation syndrome and improve the quality of life., (© 2024 The Author(s). Nursing Open published by John Wiley & Sons Ltd.)

The phytopathogenic oomycete Phytopythium helicoides, previously known as Pythium helicoides, has emerged as a new threat to the Shatangju citrus cultivar (Citrus reticulata cv. Shatangju; '' in Chinese) in southern China. To enable rapid diagnosis and control of the leaf blight and stem rot caused by P. helicoides, we developed a visualized loop-mediated isothermal amplification (LAMP) assay targeting the β-tubulin gene of the pathogen. Using a carefully selected set of primers and optimized reaction conditions at 60 °C for 60 min, the LAMP assay can specifically detect the pathogen among various citrus-associated phytopathogens. The assay demonstrated high sensitivity, detecting as little as 30 pg of the pathogen DNA, comparable to the sensitivity of quantitative polymerase chain reaction (qPCR). We validated the practical application of this LAMP assay for diagnosing infections in citrus leaves and strawberry crowns. This newly developed LAMP assay offers a specific, sensitive, and rapid detection tool for P. helicoides, aiding in the control of Shatangju citrus leaf blight and stem rot, as well as other related crop diseases like strawberry crown rot., Competing Interests: Declarations. Ethics approval: The authors declare that no human participants or animals were involved in this research. Competing interests: The authors declare no competing interests., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Background: Emodin has protective effects on acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). This meta-analysis intended to illustrate the efficacy of emodin on ALI/ARDS animal models., Methods: Relevant preclinical studies were searched on PubMed, EMBASE, and Web of Science. Standardized mean differences (SMDs) with corresponding confidence intervals (CIs) were used to compare lung injury scores, lung wet-to-dry weight ratios (W/D), myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-18, PaO 2 , and PaCO 2 between the treatment and control groups. The article quality was appraised using the SYRCLE tool., Results: Twenty one studies published between 2014 and 2023 were enrolled. Compared with the control group, emodin significantly reduced lung injury scores (SMD: -3.63; 95% CI: -4.36, -2.90; p < 0.00001), W/D ratios (SMD: -3.23; 95% CI: -4.29, -2.16; p < 0.00001), and MPO levels (SMD: -2.96; 95% CI: -3.92, -1.99; p < 0.00001). Furthermore, emodin downregulated TNF-α (SMD: -3.04; 95% CI: -3.62, -2.47; p < 0.00001), IL-1β (SMD: -3.76; 95% CI: -4.65, -2.87; p < 0.00001), IL-6 (SMD: -3.19; 95% CI: -3.95, -2.43; p < 0.00001), and IL-18 levels (SMD: -4.83; 95% CI: -6.10, -3.57; p < 0.00001). Emodin improved gas exchange dysfunction, increased PaO 2 (SMD: 3.76; 95% CI: 2.41, 5.11; p < 0.00001), and decreased PaCO 2 (SMD: -3.83; 95% CI: -4.90, -2.76; p < 0.00001). Sensitivity analyses and stratified analyses were conducted for outcome measures with heterogeneity., Conclusions: Emodin treatment can effectively reduce the severity of ALI in animal models. Additional animal investigations and clinical trials involving human subjects are imperative., Competing Interests: Declarations. Ethics approval and consent to participate: All analyses were based on previous published studies, thus no ethical approval and patient consent are required. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Scoparodane C (1), a diterpenoid with a rare 3,4-seco-3-nor-2,11-epoxy-ent-clerodane scaffold, was obtained from the aerial parts of Isodon scoparius, along with isocopariusines A-E (2-6), five ent-clerodanoids featuring a 5/6-fused ring system, and isocopariusines F-H (7-9), three common ent-clerodanoids. The structures of these previously undescribed compounds were established by a combination of spectroscopic analysis, X-ray diffraction, chemical derivatization, and quantum chemical calculation. Remarkably, isocopariusine B (3) showed strong resistance reversal activity against fluconazole-resistant Candida albicans., 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.)

Garciyunnanol A (1), an unprecedented 1,2-seco-bicyclic polyprenylated acylphloroglucinol (BPAP) possessing a unique 6/6/6 tricyclic core, was characterized from Garcinia yunnanensis together with 16 BPAPs, including eight new compounds (garciyunnanols B-I, 2-9). Biogenetically, the bicyclo[3.3.1]nonane-2,4,9-trione moiety of 12 reconstructed the bicyclic δ-lactone core of 2 through Norrish type Ⅰ cleavage and cyclization, followed by a cyclization of two side chains to form an intriguing 6/6/6 tricyclic core of 1. Their structures were elucidated through analysis of spectroscopic data, calculation and comparison of ECD spectra. Bioactivity evaluation manifested that compounds 1, 2, 5, 6 and 14 demonstrated superior inhibition of NO production compared to the positive control dexamethasone. Notably, compound 5 exhibited a dose-dependent inhibitory effect on NO production, with an IC 50 value of 0.25 ± 0.87 µM. Furthermore, experiments involving ELISA, Western blotting, and immunofluorescence staining revealed that 5 effectively reduced the secretion of interleukin-1β in LPS plus nigericin-stimulated THP-1 macrophages by inhibiting the activation of the NLRP3 inflammasome., 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.)

Plastics aging reduces resistance to microbial degradation. Plastivore Tenebrio molitor rapidly biodegrades polystyrene (PS, size: < 80 μm), but the effects of aging on PS biodegradation by T. molitor remain uncharacterized. This study examined PS biodegradation over 24 days following three pre-treatments: freezing with UV exposure (PS1), UV exposure (PS2), and freezing (PS3), compared to pristine PS (PSv) microplastic. The pretreatments deteriorated PS polymers, resulting in slightly higher specific PS consumption (602.8, 586.1, 566.7, and 563.9 mg PS·100 larvae -1 ·d -1 , respectively) and mass reduction rates (49.6 %, 49.5 %, 49.2 %, and 48.7 %, respectively) in PS1, PS2, and PS3 compared to PSv. Improved biodegradation correlated with reduced molecular weights and the formation of oxidized functional groups. Larvae fed more aged PS exhibited greater gut microbial diversity, with microbial community and metabolic pathways shaped by PS aging, as supported by co-occurrence network analysis. These findings indicated that the aging treatments enhanced PS biodegradation by only limited extent but impacted greater on gut microbiome and bacterial metabolic genes, indicating that the T. molitor host have highly predominant capability to digest PS plastics and alters gut microbiome to adapt the PS polymers fed to them., 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.)

Recently, changes in metabolites and metabolism-related enzymes related to tumor cell proliferation, metastasis, drug resistance, and immunosuppression have become a research hotspot, and researchers have attempted to determine the clinical correlation between specific molecular lesions and metabolic phenotypes. Convincing evidence shows that metabolic reprogramming is closely related to the proliferation, invasion, metastasis, and poor prognosis of malignant tumors. Therefore, targeting metabolic reprogramming is a new direction for cancer treatment. However, how molecular alterations in tumors contribute to metabolic diversity and unique targeting dependencies remains unclear. A full understanding of the underlying mechanisms of metabolic reprogramming in cancer may lead to better identification of therapeutic targets and the development of therapeutic strategies. Evidence for the importance of PCK1, a phosphoenolpyruvate carboxykinase 1, in tumorigenesis and development is accumulating. PCK1 can regulate cell proliferation and metastasis by remodeling cell metabolism. Additionally, PCK1 has "nonclassical" nonmetabolic functions, involving the regulation of gene expression, angiogenesis, epigenetic modification, and other processes, and has an impact on cell survival, apoptosis, and other biological activities, as well as the remodeling of the tumor immune microenvironment. Herein, we provide a comprehensive overview of the functions of PCK1 under physiological and pathological conditions and suggest that PCK1 is a potential target for cancer therapy. We also propose a future exploration direction for targeting PCK1 for cancer therapy from a clinical perspective. Finally, in view of the collective data, the results of our discussion suggest the potential clinical application of targeted PCK1 therapy in combination with chemotherapy and immunotherapy for cancer treatment., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Sudden sensorineural hearing loss (SSNHL) is characterized by rapid, unexplained loss of hearing within a 72-hour period and exhibits a high incidence globally. Despite this, the outcomes of therapeutic interventions remain largely unpredictable, especially for those with profound hearing loss. Extracellular vesicles (EVs), nano-sized entities containing biological materials, are implicated in the development of numerous diseases. The specific relationship between EVs and both the severity and treatment effectiveness of SSNHL, however, is not well understood., Methods: This study involved the analysis of medical records from the Department of Otolaryngology (September 1, 2020 - December 31, 2022) of patients diagnosed with SSNHL according to the 2015 Guidelines for Diagnosis and Treatment of Sudden Deafness in China. Peripheral blood samples from patients with various types of SSNHL before and after treatment were collected, alongside samples from healthy volunteers serving as controls. Plasma EVs were isolated using gel rejection chromatography and analyzed for concentration, marker presence, and morphology using Nanosight, Western blot, and transmission electron microscopy (TEM), respectively. Proteomics and miRNA assessments were conducted to identify differentially expressed proteins and miRNAs in the plasma EVs of SSNHL patients and healthy volunteers. Key proteins were further validated through Western blot analysis. Enzyme-linked immunosorbent assay (ELISA) was utilized to determine the levels of complement C3 in plasma EVs, and correlation analyses were performed with audiological data pre- and post-treatment., Results: Plasma from SSNHL patients of varying types was collected and their EVs were successfully isolated and characterized. Proteomic analysis revealed that complement C3 levels in the plasma EVs of patients with profound SSNHL were significantly higher compared to healthy controls. Differential expression of miRNAs in plasma EVs and their related functions were also identified. The study found that the level of complement C3 in plasma EVs, but not the total plasma complement C3, positively correlated with the severity of SSNHL in patients exhibiting positive therapeutic responses, particularly in those with initially lower levels of EV-associated complement C3. After treatment, complement C3 level was decreased in patients with initially higher levels of EV-associated complement C3. No significant correlation was observed between changes in plasma EV-derived complement C3 levels and the degree of hearing loss in either responders or non-responders among patients with profound SSNHL., Conclusion: Differential profiles of proteins and miRNAs were identified in patients with profound SSNHL. Notably, plasma EV-derived complement C3 was linked to both the severity and early treatment effectiveness of patients with profound SSNHL., 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.)

Muscle physiology is often perceived as a complex topic by students due to the hierarchical concepts and the need for integrative understanding. Breaking down content in a structured manner allows for segmented bite-sized learning that may enhance students' learning beyond conventional online lectures. We compared the effectiveness of (1) bite-sized structured learning (BSL) and (2) synchronous Zoom lecture (SZL) in teaching muscle physiology to first-year allied health undergraduates. For the same student cohort, the topic was divided into two lectures with the first taught via BSL, and the second via SZL. Pre- and post-quizzes were used to evaluate students' understanding of the topic. Mixed-methods online questionnaires were used to examine students' perceptions towards the two modes of learning, encompassing content coverage, delivery, engagement, effectiveness, preference and convenience. A total of 223 and 215 students completed both pre- and post-quizzes for BSL and SZL respectively. Student performances were improved via both modes (p<0.001) with a higher median score improvement in BSL when compared to SZL [3.0 (1.0-4.0) vs 2.0 (1.0-3.0)]. Among students who completed the survey, 65% expressed strong preference towards BSL over SZL (17%), which could be attributed to the benefits of self-paced microlearning such as higher motivation and improved attention. BSL was perceived to be manageable and well-structured to support learning. Our study suggests that BSL is equally effective as conventional lectures and is a learning approach favored by students. There could be merits in combining both instructional modes as their complementary advantages may enhance students' learning.

This study aimed to investigate the effect of ultrasound combined with highland barley dietary fiber (HBDF) on the quality of reduced-salt chicken breast myofibrillar protein (MP) gel. The molecular forces maintaining gel structure, the gelling formation process, and gel microstructure of different groups, two control groups (2% sodium chloride [NaCl] group, 1% NaCl group), and four treatment groups (0.3% HBDF+U5, 0.3% HBDF+U10, 0.5% HBDF+U5, and 0.5% HBDF+U10) were examined. Results indicated significant improvements (p < 0.05) in gel properties such as water-holding capacity, textural characteristics, and color of the MP gel of the four treatment groups compared to Control 2 (1% NaCl) group. Furthermore, the second structural alterations were characterized by increase β-sheet, β-turn, and random coil structure contents in treatment groups, especially in 0.3% HBDF+U5 and 0.5% HBDF+U5 groups; in addition, the exposure of more hydrophobic groups and the formation of disulfide bonds and hydrogen bonds were promoted in treatment groups, thus enhancing protein aggregation and gel quality. Finally, compared to Control 2 (1% NaCl) group, more compact and uniform gel network structures and pores inside the composite gels were observed in treatment groups. In conclusion, the findings demonstrated that the application of ultrasound in combination with HBDF improved the gelling characteristics of reduced-salt chicken breast MP gel, especially 0.3% HBDF+U5 and 0.5% HBDF+U5 groups., (© 2024 Institute of Food Technologists.)

This study aimed to investigate the effect of ultrasound treatment times (30 min and 60 min) and levels of quinoa protein (QPE) addition (1 % and 2 %) on the quality of Chinese style reduced-salt pork meatballs, commonly known as lion's head. The water-holding capacity (WHC), gel and rheology characteristics, and protein conformation were assessed. The results indicated that extending the ultrasound treatment time and elevating the quinoa protein content caused conspicuous improvements (P<0.05) in the cooking yield, WHC, textural characteristics, color difference, and salt-soluble protein (SSP) solubility of the meatballs. Furthermore, the structural alterations induced by the ultrasound treatment combined with quinoa protein addition included enhancement in β-sheet, β-turn, and random coil structure contents, along with a red-shift in the intrinsic fluorescence peak. Additionally, the storage (G') and loss modulus (G'') of the raw meatballs significantly enhanced (P<0.05), indicating a denser gel structure in parallel with the microstructure. In conclusion, the findings demonstrated that ultrasound combined with quinoa protein enhanced the WHC and texture properties of Chinese style reduced-salt pork meatballs by improving SSP solubility., 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 Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Homebound older adults (HOAs) are particularly vulnerable to social isolation and loneliness, which engender a poorer physical and mental health, and greater cognitive decline. The purpose of this review is to map the literature to identify potential technological strategies that reduce social isolation in HOAs, and to understand facilitators and barriers for adoption and implementation., Methods: Six databases including PubMed (MEDLINE), Google Scholar, Cochrane Database, EBSCOHost, National Library ProQuest, Web of Science, and the Journal of Medical Internet Research were searched for relevant articles. Peer-reviewed literature published in English from Jan 2014 to Feb 2024 that employed technological strategies applicable to HOAs and assessed social isolation or connectedness as an outcome measure were included., Results: 107 studies were reviewed and classified into different technological categories based on their functions and features. A social technology framework encompassing delivery, hardware, software, content, training, and support was conceptualized with core characteristics identified from the reviewed technological strategies. Cost and complexity of technology, and resource commitment were identified as barriers while user-friendliness, content curation and a supportive ecosystem may facilitate the adoption of a technological strategy to address social isolation in HOAs., Conclusion: There is a need for early and concerted effort to identify HOAs, provide technology training, and empower them to tap on the digital world to complement and/or supplement social interactions. Development of cost-effective and rapid-to-implement technology is vital for HOAs who are at highest risk to social isolation., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The increasing mortality rate of pancreatic cancer globally necessitates the urgent identification for novel therapeutic targets. This study investigated the expression, functions, and mechanistic insight of G protein inhibitory subunit 3 (Gαi3) in pancreatic cancer. Bioinformatics analyses reveal that Gαi3 is overexpressed in human pancreatic cancer, correlating with poor prognosis, higher tumor grade, and advanced classification. Elevated Gαi3 levels are also confirmed in human pancreatic cancer tissues and primary/immortalized cancer cells. Gαi3 shRNA or knockout (KO) significantly reduced cell viability, proliferation, cell cycle progression, and mobility in primary/immortalized pancreatic cancer cells. Conversely, Gαi3 overexpression enhanced pancreatic cancer cell growth. RNA-sequencing and bioinformatics analyses of Gαi3-depleted cells indicated Gαi3's role in modulating the Akt-mTOR and PKA-Hippo-YAP pathways. Akt-S6 phosphorylation was decreased in Gαi3-depleted cells, but was increased with Gαi3 overexpression. Additionally, Gαi3 depletion elevated PKA activity and activated the Hippo pathway kinase LATS1/2, leading to YAP/TAZ inactivation, while Gαi3 overexpression exerted the opposite effects. There is an increased binding between Gαi3 promoter and the transcription factor TCF7L2 in pancreatic cancer tissues and cells. Gαi3 expression was significantly decreased following TCF7L2 silencing, but increased with TCF7L2 overexpression. In vivo, intratumoral injection of Gαi3 shRNA-expressing adeno-associated virus significantly inhibited subcutaneous pancreatic cancer xenografts growth in nude mice. A significant growth reduction was also observed in xenografts from Gαi3 knockout pancreatic cancer cells. Akt-mTOR inactivation and increased PKA activity coupled with YAP/TAZ inactivation were also detected in xenograft tumors upon Gαi3 depletion. Furthermore, bioinformatic analysis and multiplex immunohistochemistry (mIHC) staining on pancreatic cancer tissue microarrays showed a reduced proportion of M1-type macrophages and an increase in PD-L1 positive cells in Gαi3-high pancreatic cancer tissues. Collectively, these findings highlight Gαi3's critical role in promoting pancreatic cancer cell growth, potentially through the modulation of the Akt-mTOR and PKA-Hippo-YAP pathways and its influence on the immune landscape., (© 2024. The Author(s).)

Covalent organic framework (COF) film with electrofluorochromic (EFC) and electrochromic (EC) properties has been synthesized by using triphenylamine-based monomers. The film exhibited a high maximum fluorescence contrast of 151 when subjected to a drive voltage of 0.75 V vs the Ag/AgCl electrode, causing the fluorescence to be quenched, which resulted in the EFC process's "fluorescence off" state. The switching times for the fluorescence on and off states were 0.51 and 7.79 s, respectively. Over the same voltage range, the COF film also displayed EC properties, achieving a contrast of 50.23% and a coloration efficiency of 297.4 cm 2 C -1 at 532 nm, with switching times of 18.6 s for coloration and 0.7 s for bleaching. Notably, the quenched fluorescence of the COF film could be restored by adding dopamine as a reductant. This phenomenon enabled the implementation of a NAND logic gate using the applied potential as a physical input and dopamine addition as a chemical input. This study demonstrates the successful development of COF films with bifunctional EFC and EC properties, showcasing their potential for use in constructing advanced optoelectronic devices.

Ethnopharmacological Relevance: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study., Aim of the Study: To evaluate the effect of BL on improving PCOS in mice and explore the mechanism., Methods: In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested., Results: The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank&#95;f&#95;&#95;Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated., Conclusion: The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS., Competing Interests: Declaration of competing interest The authors declare that none of the work reported in this study could have been influenced by any known competing financial interests or personal relationships., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Isoxerophilusins A ( 1 ) and B ( 2 ), two unprecedented diterpene heterodimers biogenetically from ent -atisanes and abietanes, were isolated from the rhizomes of Isodon xerophilus . Their structures were determined by extensive spectroscopic analysis and single-crystal X-ray diffraction. Selective esterification of 1 generated 11 new derivatives. All derivatives showed excellent α -glucosidase inhibitory activity in comparison to acarbose. Compounds 12 and 13 demonstrated significant inhibition against α -glucosidase with IC 50 values of 4.92 and 3.83 μ M, respectively.

The metal-free porphyrins protonation has gained interest over five decades because its structure modification and hardly monoacid intermediate isolation. Here, upon the hydrogen atom abstraction processes, one step diproptonated H 3 STTP(BF 4 ) 2 (STTP = 5,10,15,20-tetraphenyl-21-thiaporphyrin) ( 3 ) and stepwise protonated HS 2 TTPSbCl 6 ( 5 ) and diprotonated H 2 S 2 TTP(BF 4 ) 2 ( 6 ) (S 2 TTP = 5,10,15,20-tetraphenyl-21,23-thiaporphyrin) compounds were obtained using HSTTP and S 2 TTP with oxidants. The closed-shell protonated compounds were fully characterized using XRD, UV-vis, IR and NMR spectra. In addition, the reduced 19π compounds [K(2,2,2)]HSTTP ( 2 ) and [K(2,2,2)]S 2 TTP ( 7 ) were synthesized by the ligands with reductant KC 8 in THF solution. These two open-shell compounds were characterized with UV-vis, IR and EPR spectroscopies. The semiempirical ZINDO/S method was employed to analyze the HOMO/LUMO gap lever and identify the electronic transitions of the UV-vis spectra of the closed- and open-shell porphyrin compounds.

We present a novel approach for measuring the differential static scalar polarizability of a target ion utilizing a "polarizability scale" scheme with a reference ion co-trapped in a linear Paul trap. The differential static scalar polarizability of the target ion can be precisely extracted by measuring the ratio of the ac Stark shifts induced by an add-on infrared laser shed on both ions. This method circumvents the need for the calibration of the intensity of the add-on laser, which is usually the bottleneck for measurements of the polarizability of trapped ions. As a demonstration, ^{27}Al^{+} (the target ion) and ^{40}Ca^{+} (the reference ion) are used in this work, with an add-on laser at 1068 nm injected into the ion trap along the trap axis. The differential static scalar polarizability of ^{27}Al^{+} is extracted to be 0.416(14) a.u. by measuring the ratio of the ac Stark shifts of both ions. Compared to the most recent result [Phys. Rev. Lett. 123, 033201 (2019)PRLTAO0031-900710.1103/PhysRevLett.123.033201], the relative uncertainty of the differential static scalar polarizability of ^{27}Al^{+} is reduced by approximately a factor of 4, to 3.4%. This improvement is expected to be further enhanced by using an add-on laser with a longer wavelength.

Ethnopharmacological Relevance: Pitongshu (PTS) is a clinically effective empirical formula for the treatment of FD. The efficacy and safety of PTS have been demonstrated in randomized, controlled, double-blind trials, but there is a lack of understanding of the systematic evaluation of the efficacy of PTS and its material basis., Objective: To investigate the efficacy of PTS in Functional dyspepsia (FD) mice and possible Q-markers., Method: In this study, we used "irregular feeding + chronic unpredictable chronic stimulation" to establish a mice model of FD with hepatogastric disharmony. The efficacy of PTS was assessed from hair condition, behavioral, pain, gastrointestinal function, and serum 5-HT, GAS, MTL levels in mice by instillation of different doses of PTS. In addition, the composition of drugs in blood was analyzed by LC-QTOF-MS and potential Q-markers were selected by combining network pharmacology, molecular docking and actual content., Result: Our study showed that different doses of PTS increased pain threshold and writhing latency, decreased the number of writhings, increased gastric emptying rate and small intestinal propulsion rate, decreased total acidity of gastric contents and gastric acid secretion, and increased serum levels of 5-HT, GAS, and MTL in mice to different degrees. Enrichment analysis showed that PTS may be anti-FD through multiple pathways such as Serotonergic synapse, thyroid hormone signaling pathway, cholinergic synapse, and dopaminergic synapse. In addition, potential active ingredient substances were explored by LC-QTOF-MS combined with bioinformatics. Combined with the actual contentselected six constituents, hesperidin, neohesperidin, naringin, paeoniflorin, magnolol and honokiol, possible as Q-markers., Conclusion: PTS may exert its anti-FD effects through multi-component, multi-target and multi-pathway". Constituents, hesperidin, neohesperidin, naringin, paeoniflorin, magnolol and honokiol may be the Q-markers of its anti-FD 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.)

Most of kiwifruit cultivars (e.g. Actinidia chinensis cv. Donghong, "DH") were sensitive to waterlogging, thus, waterlogging resistant rootstocks (e.g. Actinidia valvata Dunn, "Dunn") were widely used for kiwifruit industry. Those different species provided ideal materials to understand the waterlogging responses in kiwifruit. Compared to the weaken growth and root activities in "DH", "Dunn" maintained the relative high root activities under the prolonged waterlogging. Based on comparative analysis, transcript levels of pyruvate decarboxylase (PDCs) and alcohol dehydrogenase (ADHs) showed significantly difference between these two species. Both PDCs and ADHs had been significantly increased by waterlogging in "DH", while they were only limitedly triggered by 2 days stress and subsided during the prolonged waterlogging in "Dunn". Thus, 19 differentially expressed transcript factors (DETFs) had been isolated using weighted gene co-expression network analysis combined with transcriptomics and transcript levels of PDCs and ADHs in waterlogged "DH". Among these DETFs, dual luciferase and electrophoretic mobility shift assays indicated AcMYB68 could bind to and trigger the activity of AcPDC2 promoter. The stable over-expression of AcMYB68 significantly up-regulated the transcript levels of PDCs but inhibited the plant growth, especially the roots. Moreover, the enzyme activities of PDC in 35S::AcMYB68 were significantly enhanced during the waterlogging response than that in wild type plants. Most interestingly, comparative analysis indicated that the expression patterns of AcMYB68 and the previously characterized AcERF74/75 (the direct regulator on ADHs) either showed no responses (AcMYB68 and AcERF74) or very limited response (AcERF75) in "Dunn". Taken together, the restricted responses of AcMYB68 and AcERF74/75 in "Dunn" endow its waterlogging tolerance., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Background: Recently, male fertility preservation before cancer treatment has become more prevalent. The research in this field has progressed over time, with some studies having a major impact and providing guidance for further research. However, the trends and hotspots of research on fertility preservation in male cancer patients may have changed; exploring them is essential for relevant research progress., Design: We extracted relevant studies from the Web of Science Core Collection database, capturing information on the countries of study, affiliations, authors, keywords, as well as co-citations of references and journals. To identify publication trends, research strengths, key subjects, prominent topics, and emerging areas, we conducted a bibliometric analysis using CiteSpace., Results: We included 3201 articles on fertility preservation in male cancer patients published over January 1999 to December 2023 were included. Although the relevant research growth rate was slow initially, the number of publications increased annually. Of all study countries, the United States, Germany, and Japan reported the earliest studies; the United States published the highest number of relevant studies. The US institutions remained at the forefront for all 25 years, and the US researcher Ashok Agarwal published the most articles. Literature co-citation analyses indicated a transformation in the study participants; they comprised a younger demographic (i.e., a large number of adolescent male patients underwent fertility preservation); moreover, fertility preservation techniques evolved from sperm cryopreservation to testicular tissue cryopreservation. Research on reproductive outcomes of sperm cryopreservation was the recent hotspot in male fertility preservation research, and the impact of immunotherapy and checkpoint inhibitors on male fertility requires further research., Conclusions: Male fertility preservation will be a major future research focus, with closer connections and collaborations between countries and organizations. Our results present the historical data on the development of research on male fertility preservation in cancer patients, providing relevant insights for future research and development in this study area., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Gastric bronchogenic cysts (BCs) are extremely rare cystic masses caused by abnormal development of the respiratory system during the embryonic period. Gastric bronchial cysts are rare lesions that were first reported in 1956; as of 2023, only 33 cases are available in the PubMed online database. BCs usually have no clinical symptoms in the early stage, and imaging findings also lack specificity. Therefore, they are difficult to diagnose before histopathological examination., Case Summary: A 34-year-old woman with respiratory distress presented at our hospital. Endoscopic ultrasound revealed an anechoic mass between the spleen, left kidney and gastric fundus, with hyperechogenic and soft elastography textures and with a size of approximately 6.5 cm × 4.0 cm. Furthermore, a computed tomography scan demonstrated high density between the posterior stomach and the spleen and the left kidney, with uniform internal density and a small amount of calcification. The maximum cross section was approximately 10.1 cm × 6.1 cm, and the possibility of a cyst was high. Because the imaging findings did not suggest a malignancy and because the patient required complete resection, she underwent laparotomy surgery. Intraoperatively, this cystic lesion was found to be located in the posterior wall of the large curvature of the fundus and was approximately 8 cm × 6 cm in size. Finally, the pathologists verified that the cyst in the fundus was a gastric BC. The patient recovered well, her symptoms of chest tightness disappeared, and the abdominal drain was removed on postoperative day 6, after which she was discharged on day 7 for 6 months of follow-up. She had no tumor recurrence or postoperative complications during the follow-up., Conclusion: This is a valuable report as it describes an extremely rare case of gastric BC. Moreover, this was a very young patient with a large BC in the stomach., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Pericentric inversion of chromosome 9 (inv[9]) is a common chromosomal structural variant, but its impact on clinical outcomes remains debated. The screening criteria of sperm banks are rarely mentioned to individuals with inv(9). In this study, we evaluated the fertility of sperm donors with inv(9) who met eligibility criteria for sperm banks (inv[9]-eligible donors). From March 2004 to May 2022, chromosomal analysis of 16 124 sperm donors at CITIC-Xiangya Human Sperm Bank in Hunan Province (Changsha, China) found that 251 (1.6%) had chromosome variations, with inv(9) being the most prevalent at 1.1%. All 169 inv(9)-eligible donors were contacted to collect fertility outcome data, along with 206 eligible donors without inv(9) as controls. In addition, semen samples from inv(9)-eligible donors and eligible donors underwent assessments of sperm fluorescence in situ hybridization (FISH), mitochondrial membrane potential, DNA fragmentation index, acrosome integrity, reactive oxygen species (ROS), and sperm morphology. Results showed that inv(9) did not significantly increase reproductive risks overall. Despite detecting ROS level differences, the clinical impact may be insignificant. This study provides new data on the inv(9) population that can serve as a valuable reference for decision-making by sperm banks as well as for genetic counseling and clinical guidance for individuals carrying inv(9) variant., (Copyright © 2024 Copyright: © The Author(s)(2024).)

MicroRNAs (miRNAs) are a class of nonprotein-coding short transcripts that provide a layer of post-transcriptional regulation essential to many plant biological processes. MiR858, which targets the transcripts of MYB transcription factors, can affect a range of secondary metabolic processes. Although miR858 and its 187-nt precursor have been well studied in Arabidopsis (Arabidopsis thaliana), a systematic investigation of miR858 precursors and their functions across plant species is lacking due to a problem in identifying the transcripts that generate this subclass. By re-evaluating the transcript of miR858 and relaxing the length cut-off for identifying hairpins, we found in kiwifruit (Actinidia chinensis) that miR858 has long-loop hairpins (1,100 to 2,100 nt), whose intervening sequences between miRNA generating complementary sites were longer than all previously reported miRNA hairpins. Importantly, these precursors of miR858 containing long-loop hairpins (termed MIR858L) are widespread in seed plants including Arabidopsis, varying between 350 and 5,500 nt. Moreover, we showed that MIR858L has a greater impact on proanthocyanidin and flavonol levels in both Arabidopsis and kiwifruit. We suggest that an active MIR858L-MYB regulatory module appeared in the transition of early land plants to large upright flowering plants, making a key contribution to plant secondary metabolism., Competing Interests: Conflict of interest statement. The authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Accumulating evidence underscores the pivotal role of envelope proteins in viral secondary envelopment. However, the intricate molecular mechanisms governing this phenomenon remain elusive. To shed light on these mechanisms, we investigated a Golgi-retained gD of EHV-1 (gD EHV-1 ), distinguishing it from its counterparts in Herpes Simplex Virus-1 (HSV-1) and Pseudorabies Virus (PRV). To unravel the specific sequences responsible for the Golgi retention phenotype, we employed a gene truncation and replacement strategy. The results suggested that Golgi retention signals in gD EHV-1 exhibiting a multi-domain character. The extracellular domain of gD EHV-1 was identified as an endoplasmic reticulum (ER)-resident domain, the transmembrane domain and cytoplasmic tail (TM-CT) of gD EHV-1 were integral in facilitating the protein's residence within the Golgi complex. Deletion or replacement of either of these dual domains consistently resulted in the mutant gD EHV-1 being retained in an ER-like structure. Moreover, (TM-CT) EHV-1 demonstrated a preference for binding to endomembranes, inducing the generation of a substantial number of vesicles, potentially originate from the Golgi complex or the ER-Golgi intermediate compartment. In conclusion, our findings provide insights into the intricate molecular mechanisms governing the Golgi retention of gD EHV-1 , facilitating the comprehension of the processes underlying viral secondary envelopment., Competing Interests: Declaration of competing interest The authors declare that they have no 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.)

Pre-exercise passive heating attenuates muscle damage caused by eccentric exercise in rats where the induction of heat shock proteins (HSPs) confers a myoprotective effect. We investigated whether pre-exercise hot water immersion (HWI) confers similar benefits in humans. Eleven recreational male athletes were immersed in 41°C water up to 60 min or until rectal temperatures reached 39.5°C. After a 6 h rest, the participants performed an eccentric downhill run for 1 h at -4% gradient to induce muscle damage. An endurance capacity test at 75% VO 2max was conducted 18 h later. The control trial was similar except that participants were immersed at 34°C. Blood samples were collected to assess HSPs levels, creatine kinase, and lactate dehydrogenase activities. Plasma eHSP70 was higher post-immersion in HWI trials (1.3 ± 0.4 vs 1.1 ± 0.4; p  = 0.005). Plasma eHSP27 was higher before ( p  = 0.049) and after ( p  = 0.015) endurance test in HWI. Leukocytic p-HSP27 was increased 18 h after HWI (0.97 ± 0.14 vs 0.67 ± 0.11; p  = 0.04). Creatine kinase and lactate dehydrogenase activities were increased by 3-fold and 1.5-fold, respectively, after endurance test in HWI but did not differ across trials ( p  > 0.05). Mean heart rates were higher during eccentric run and endurance test in HWI as compared to control ( p  < 0.05). Endurance capacity was similar between trials (57.3 ± 11.5 min vs 55.0 ± 13.5 min; p  = 0.564). Pre-exercise heating increased the expression of plasma eHSPs and leukocytic p-HSP27 but did not reduce muscle damage nor enhance endurance capacity., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Objective: To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China. Methods: This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis. Results: Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z= 1.30, P= 0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs . 4(3, 7) points, Z= 6.56, P< 0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs . 82(76, 88) points, Z= 5.90, P< 0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z= 6.59, 4.23, both P< 0.001). There was no significant difference between pSOFA and PCIS ( Z= 1.35, P= 0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P< 0.05). Conclusion: Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

Background: Excessive heat exposure can lead to hyperthermia in humans, which impairs physical performance and disrupts cognitive function. While heat is a known physiological stressor, it is unclear how severe heat stress affects brain physiology and function., Methods: Eleven healthy participants were subjected to heat stress from prolonged exercise or warm water immersion until their rectal temperatures (T re ) attained 39.5°C, inducing exertional or passive hyperthermia, respectively. In a separate trial, blended ice was ingested before and during exercise as a cooling strategy. Data were compared to a control condition with seated rest (normothermic). Brain temperature (T br ), cerebral perfusion, and task-based brain activity were assessed using magnetic resonance imaging techniques., Results: T br in motor cortex was found to be tightly regulated at rest (37.3°C ± 0.4°C (mean ± SD)) despite fluctuations in T re . With the development of hyperthermia, T br increases and dovetails with the rising T re . Bilateral motor cortical activity was suppressed during high-intensity plantarflexion tasks, implying a reduced central motor drive in hyperthermic participants (T re  = 38.5°C ± 0.1°C). Global gray matter perfusion and regional perfusion in sensorimotor cortex were reduced with passive hyperthermia. Executive function was poorer under a passive hyperthermic state, and this could relate to compromised visual processing as indicated by the reduced activation of left lateral-occipital cortex. Conversely, ingestion of blended ice before and during exercise alleviated the rise in both T re and T br and mitigated heat-related neural perturbations., Conclusion: Severe heat exposure elevates T br , disrupts motor cortical activity and executive function, and this can lead to impairment of physical and cognitive performance., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Background: Bone or brain metastases may develop in 20-40% of individuals with late-stage non-small-cell lung cancer (NSCLC), resulting in a median overall survival of only 4-6 months. However, the primary lung cancer tissue's distinctions between bone, brain and intrapulmonary metastases of NSCLC at the single-cell level have not been underexplored., Methods: We conducted a comprehensive analysis of 14 tissue biopsy samples obtained from treatment-naïve advanced NSCLC patients with bone (n = 4), brain (n = 6) or intrapulmonary (n = 4) metastasis using single-cell sequencing originating from the lungs. Following quality control and the removal of doublets, a total of 80 084 cells were successfully captured., Results: The most significant inter-group differences were observed in the fraction and function of fibroblasts. We identified three distinct cancer-associated fibroblast (CAF) subpopulations: myofibroblastic CAF (myCAF), inflammatory CAF (iCAF) and antigen-presenting CAF (apCAF). Notably, apCAF was prevalent in NSCLC with bone metastasis, while iCAF dominated in NSCLC with brain metastasis. Intercellular signalling network analysis revealed that apCAF may play a role in bone metastasis by activating signalling pathways associated with cancer stemness, such as SPP1-CD44 and SPP1-PTGER4. Conversely, iCAF was found to promote brain metastasis by activating invasion and metastasis-related molecules, such as MET hepatocyte growth factor. Furthermore, the interaction between CAFs and tumour cells influenced T-cell exhaustion and signalling pathways within the tumour microenvironment., Conclusions: This study unveils the direct interplay between tumour cells and CAFs in NSCLC with bone or brain metastasis and identifies potential therapeutic targets for inhibiting metastasis by disrupting these critical cell-cell interactions., (© 2024 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Background: Hepatic cystic and alveolar echinococcosis coinfections, particularly with concurrent abscesses and sinus tract formation, are extremely rare. This article presents a case of a patient diagnosed with this unique presentation, discussing the typical imaging manifestations of both echinococcosis types and detailing the diagnosis and surgical treatment experience thereof., Case Summary: A 39-year-old Tibetan woman presented with concurrent hepatic cystic and alveolar echinococcosis, accompanied by abdominal wall abscesses and sinus tract formation. Initial conventional imaging examinations suggested only hepatic cystic echinococcosis, but intraoperative and postoperative pathological examination revealed the coinfection. Following radical resection of the lesions, the patient's condition improved, and she was discharged soon thereafter. Subsequent outpatient follow-ups confirmed no recurrence of the hydatid lesion and normal surgical wound healing. Though mixed hepatic cystic and alveolar echinococcosis with abdominal wall abscesses and sinus tract formations are rare, the general treatment approach remains consistent with that of simpler infections of alveolar echinococcosis., Conclusion: Lesions involving the abdominal wall and sinus tract formation, may require radical resection. Long-term prognosis includes albendazole and follow-up examinations., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Exploitation of key protected wild plant resources makes great sense, but their limited populations become the major barrier. A particular strategy for breaking this barrier was inspired by the exploration of a resource-saving fungal endophyte Penicillium sp. DG23, which inhabits the key protected wild plant Schisandra macrocarpa. Chemical studies on the cultures of this strain afforded eight novel indole diterpenoids, schipenindolenes A-H (1-8), belonging to six diverse skeleton types. Importantly, semisyntheses suggested some key nonenzymatic reactions constructing these molecules and provided targeted compounds, in particular schipenindolene A (Spid A, 1) with low natural abundance. Remarkably, Spid A was the most potent HMG-CoA reductase (HMGCR) degrader among the indole diterpenoid family. It degraded statin-induced accumulation of HMGCR protein, decreased cholesterol levels and acted synergistically with statin to further lower cholesterol. Mechanistically, transcriptomic and proteomic profiling suggested that Spid A potentially activated the endoplasmic reticulum-associated degradation (ERAD) pathway to enhance the degradation of HMGCR, while simultaneously inhibiting the statin-activated expression of many key enzymes in the cholesterol and fatty acid synthesis pathways, thereby strengthening the efficacy of statins and potentially reducing the side effects of statins. Collectively, this study suggests the potential of Spid A for treating cardiovascular disease., (© 2023 Wiley-VCH GmbH.)

Stimbiotic supplementation may provide an innovative feed additive solution to accelerate the proliferation of beneficial fiber-degrading bacteria in the distal intestine and the utilization of dietary fiber. Optimal utilization of dietary fiber has multiple benefits for gut health and nutrient utilization. This study was conducted to evaluate the late gestation and lactation performance, the plasma, colostrum, and milk immunoglobulin (IgA, IgG, and IgM) concentrations, and the anti-inflammatory and antioxidant biomarkers in plasma of sows fed with or without a stimbiotic during the late gestation and lactation phase. A total of 40 sows were allocated to two treatment groups: control (CT) with no supplementation or 100 mg/kg stimbiotic (VP), with 20 sows per treatment. Sows were fed the treatment diets from d 85 of gestation to d 28 of lactation. In the results, the average daily weight gain of piglets during lactation was greater from sows fed in the VP group compared to that in the CT group ( p < 0.05). The plasma concentrations of IgM at farrowing and IgG at weaning of the sows fed the diet with the stimbiotic supplementation were much higher than those in the CT sows ( p < 0.05), respectively. In addition, the dietary stimbiotic increased the concentrations of IgM in the colostrum and of IgA and IgM in the milk at d 14 of lactation ( p < 0.05). Plasma concentrations of malondialdehyde (MDA) on d 0 and d 28 of lactation tended to be lower in sows fed the VP diets compared with those of the sows fed the CT diets. Thus, our study indicated that stimbiotic supplementation could improve the daily weight gain of piglets and the immune function of sows in lactation.

A smart home sleep respiratory monitoring system based on a breath-responsive covalent organic framework (COF) was developed and utilized to monitor the sleep respiratory behavior of real sleep apnea patients in this work. The capacitance of the interdigital electrode chip coated with COF TPDA-TFPy exhibits thousands-level reversible responses to breath humidity gases, with subsecond response time and robustness against environmental humidity. A miniaturized printed circuit board, an open-face-mask-based respiratory sensor, and a smartphone app were constructed for the wearable wireless smart home sleep respiratory monitoring system. Leveraging the sensitive and rapid reversible response of COFs, the COF-based respiratory monitoring system can effectively record normal breath, rapid breath, and breath apnea, enabling over a thousand cycles of hour-level continuous monitoring during daily wear. Next, we took the groundbreaking step of advancing the humidity sensor to the clinical trial stage. In clinical experiments on real sleep apnea patients, the COF-based respiratory monitoring system successfully recorded hour-level sleep respiratory data and differentiated the breathing behavior characteristics and severity of sleep apnea patients and subjects with normal sleep function and primary snoring patients. This work successfully advanced humidity sensors into clinical research for real patients and demonstrated the enormous application potential of COF materials in clinical diagnosis.

The global practice of cryopreservation of human semen is commonplace in Assisted Reproductive Technology (ART) labs and sperm banks. However, information on the effects of long-term cryopreservation on semen is limited to clinical data summaries and descriptions. For this study, we prepared 4 semen specimens of fresh semen, 4 specimens cryostored for at least 1 year, 3 specimens cryostored for at least 5 years, 4 specimens cryostored for at least 10 years, and 3 specimens cryostored for at least 15 years. Total RNA was extracted from each sample, amplified, labeled, and mapped to the known primary microRNA (miRNA) in the miRBase database, enabling the prediction of novel miRNAs. We found that cryopreservation can lead to changes in miRNA expression, and with the increase in storage time, these changes became more pronounced. Meanwhile, the expression of let-7d-3p, let-7c-5p and let-7i-3p miRNAs changed dynamically over cryostorage time in frozen-thawed human sperm. Furthermore, we analyzed the time-dependent dynamics of cryostorage-expressed miRNAs and their target mRNAs and found that half of the target genes were expressed in oocytes. These intersection genes were mainly enriched in cancer and cytoskeletal signaling pathways. Our findings showed that the miRNA expression profile of cryopreserved human semen is modified by long-term storage. Furthermore, as the storage time increases, the impact on human sperm becomes more pronounced in terms of miRNAs, which may have an effect on subsequent fertilization and embryonic development.

The proteins were mainly derived from Protaetia brevitarsis larval extracts obtained using two empty intestine methods (traditional static method: TSM or salt immersion stress method: SISM) and extraction solvents (water: W or 50 % water-ethanol: W:E), and the proteins were used as objects to investigate the effect of emptying intestine methods on hypolipidemic peptides. The results revealed that the F-2 fractions of protein hydrolysate had stronger in vitro hypolipidemic activity, with the peptides obtained by SISM possessing a stronger cholesterol micelle solubility inhibition rate, especially in SISM-W:E-P. Moreover, a total of 106 peptides were tentatively identified, among which SISM identified more peptides with an amino acid number < 8. Meanwhile, five novel peptides (YPPFH, YPGFGK, KYPF, SPLPGPR and VPPP) exhibited good hypolipidemic activity in vitro and in vivo, among which YPPFH, VPPP and KYPF had strong inhibitory activities on pancreatic lipase (PL) and cholesteryl esterase (CE), and KYPF, SPLPGPR and VPPP could significantly reduce the TG content in Caenorhabditis elegans. Thus, P. brevitarsis can be developed as a naturally derived hypolipidemic component for the development and application in functional foods., 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 © 2023 Elsevier Ltd. All rights reserved.)

The degradation of chlorophyll during fruit development is essential to reveal a more 'ripe' color that signals readiness to wild dispersers of seeds and the human consumer. Here, comparative biochemical analysis of developing fruit of Actinidia deliciosa cv. Xuxiang ('XX', green-fleshed) and Actinidia chinensis cv. Jinshi No.1 ('JS', yellow-fleshed) indicated that variation in chlorophyll content is the major contributor to differences in flesh color. Four differentially expressed candidate genes were identified: the down-regulated genes AcCRD1 and AcPOR1 involved in chlorophyll biosynthesis, and the up-regulated genes AcSGR1 and AcSGR2 driving chlorophyll degradation. Prochlorophyllide and chlorophyllide, the metabolites produced by AcCRD1 and AcPOR1, progressively reduced in 'JS', but not in 'XX', indicating that chlorophyll biosynthesis was less active in yellow-fleshed fruit. AcSGR1 and AcSGR2 were verified to be involved in chlorophyll degradation, using both transient expression in tobacco and stable overexpression in kiwifruit. Furthermore, a homeobox-leucine zipper (HD-Zip II), AcHZP45, showed significantly increased expression during 'JS' fruit ripening, which led to both repressed expression of AcCRD1 and AcPOR1 and activated expression of AcSGR1 and AcSGR2. Collectively, the present study indicated that different dynamics of chlorophyll biosynthesis and degradation coordinate the changes in chlorophyll content in kiwifruit flesh, which are orchestrated by the key transcription factor AcHZP45., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Fruits are highly recommended nowadays in human diets because they are rich in vitamins, minerals, fibers and other necessary nutrients. The final stage of fruit production, known as ripening, plays a crucial role in determining the fruit's quality and commercial value. This is a complex physiological process, which involves many phytohormones and regulatory factors. Among the phytohormones involved in fruit ripening, abscisic acid (ABA) holds significant importance. ABA levels generally increase during the ripening process in most fruits, and applying ABA externally can enhance fruit flavor, hasten softening, and promote color development through complex signal regulation. Therefore, gaining a deeper understanding of ABA's mechanisms in fruit ripening is valuable for regulating various fruit characteristics, making them more suitable for consumption or storage. This, in turn, can generate greater economic benefits and reduce postharvest losses. This article provides an overview of the relationship between ABA and fruit ripening. It summarizes the effects of ABA on ripening related traits, covering the biochemical aspects and the underlying molecular mechanisms. Additionally, the article discusses the interactions of ABA with other phytohormones during fruit ripening, especially ethylene, and provides perspectives for future exploration in this field., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Wu, Cao, Shi, Chen, Yin and Yang.)

Pharmacological agents used to treat or manage diseases can modify the level of heat strain experienced by chronically ill and elderly patients via different mechanistic pathways. Human thermoregulation is a crucial homeostatic process that maintains body temperature within a narrow range during heat stress through dry (i.e., increasing skin blood flow) and evaporative (i.e., sweating) heat loss, as well as active inhibition of thermogenesis, which is crucial to avoid overheating. Medications can independently and synergistically interact with aging and chronic disease to alter homeostatic responses to rising body temperature during heat stress. This review focuses on the physiologic changes, with specific emphasis on thermolytic processes, associated with medication use during heat stress. The review begins by providing readers with a background of the global chronic disease burden. Human thermoregulation and aging effects are then summarized to give an understanding of the unique physiologic changes faced by older adults. The effects of common chronic diseases on temperature regulation are outlined in the main sections. Physiologic impacts of common medications used to treat these diseases are reviewed in detail, with emphasis on the mechanisms by which these medications alter thermolysis during heat stress. The review concludes by providing perspectives on the need to understand the effects of medication use in hot environments, as well as a summary table of all clinical considerations and research needs of the medications included in this review. SIGNIFICANCE STATEMENT: Long-term medications modulate thermoregulatory function, resulting in excess physiological strain and predisposing patients to adverse health outcomes during prolonged exposures to extreme heat during rest and physical work (e.g., exercise). Understanding the medication-specific mechanisms of altered thermoregulation has importance in both clinical and research settings, paving the way for work toward refining current medication prescription recommendations and formulating mitigation strategies for adverse drug effects in the heat in chronically ill patients., (Copyright © 2023 by The Author(s).)

Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. NSCLC patients often have poor prognosis demanding urgent identification of novel biomarkers and potential therapeutic targets. KCNAB2 (regulatory beta subunit2 of voltage-gated potassium channel), encoding aldosterone reductase, plays a pivotal role in regulating potassium channel activity. In this research, we tested the expression of KCNAB2 as well as its potential functions in human NSCLC. Bioinformatics analysis shows that expression of KCNAB2 mRNA is significantly downregulated in human NSCLC, correlating with poor overall survival. In addition, decreased KCNAB2 expression was detected in different NSCLC cell lines and local human NSCLC tissues. Exogenous overexpression of KCNAB2 potently suppressed growth, proliferation and motility of established human NSCLC cells and promoted NSCLC cells apoptosis. In contrast, CRISPR/Cas9-induced KCNAB2 knockout further promoted the malignant biological behaviors of NSCLC cells. Protein chip analysis in the KCNAB2-overexpressed NSCLC cells revealed that KCNAB2 plays a possible role in AKT-mTOR cascade activation. Indeed, AKT-mTOR signaling activation was potently inhibited following KCNAB2 overexpression in NSCLC cells. It was however augmented by KCNAB2 knockout. In vivo, the growth of subcutaneous KCNAB2-overexpressed A549 xenografts was significantly inhibited. Collectively, KCNAB2 could be a novel effective gene for prognosis prediction of NSCLC. Targeting KCNAB2 may lead to the development of advanced therapies., (© 2023. Cell Death Differentiation Association (ADMC).)

Phytophthora cactorum is one of the most economically important soilborne oomycete pathogens in the world. It infects more than 200 plant species spanning 54 families, most of which are herbaceous and woody species. Although traditionally considered to be a generalist, marked differences of P. cactorum isolates occur in degree of pathogenicity to different hosts. As the impact of crop loss caused by this species has increased recently, there has been a tremendous increase in the development of new tools, resources, and management strategies to study and combat this devastating pathogen. This review aims to integrate recent molecular biology analyses of P. cactorum with the current knowledge of the cellular and genetic basis of its growth, development, and host infection. The goal is to provide a framework for further studies of P. cactorum by highlighting important biological and molecular features, shedding light on the functions of pathogenicity factors, and developing effective control measures., Taxonomy: P. cactorum (Leb. & Cohn) Schröeter: kingdom Chromista; phylum Oomycota; class Oomycetes; order Peronosporales; family Peronosporaceae; genus Phytophthora., Host Range: Infects about 200 plant species in 154 genera representing 54 families. Economically important host plants include strawberry, apple, pear, Panax spp., and walnut., Disease Symptoms: The soilborne pathogen often causes root, stem, collar, crown, and fruit rots, as well as foliar infection, stem canker, and seedling damping off., (© 2023 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

As the harvest season of most fruit is concentrated, fruit maturation manipulation is essential for the fresh fruit industry to prolong sales time. Gibberellin (GA), an important phytohormone necessary for plant growth and development, has also shown a substantial regulatory effect on fruit maturation; however, its regulatory mechanisms remain inconclusive. In this research, preharvest GA3 treatment effectively delayed fruit maturation in several persimmon (Diospyros kaki) cultivars. Among the proteins encoded by differentially expressed genes, 2 transcriptional activators (NAC TRANSCRIPTION FACTOR DkNAC24 and ETHYLENE RESPONSIVE FACTOR DkERF38) and a repressor (MYB-LIKE TRANSCRIPTION FACTOR DkMYB22) were direct regulators of GERANYLGERANYL DIPHOSPHATE SYNTHASE DkGGPS1, LYSINE HISTIDINE TRANSPORTER DkLHT1, and FRUCTOSE-BISPHOSPHATE ALDOLASE DkFBA1, respectively, resulting in the inhibition of carotenoid synthesis, outward transport of an ethylene precursor, and consumption of fructose and glucose. Thus, the present study not only provides a practical method to prolong the persimmon fruit maturation period in various cultivars but also provides insights into the regulatory mechanisms of GA on multiple aspects of fruit quality formation at the transcriptional regulation level., Competing Interests: Conflict of interest statement. None declared., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Echinococcosis is a zoonotic parasitic disease caused by Escherichia larvae. It frequently involves the liver (70%-75%), followed by the lungs (15%-20%), and occasionally the brain, heart, spleen, bone, and other organs. The main pathogenic forms of human echinococcosis currently include cystic echinococcosis (CE) and alveolar echinococcosis (AE). CE is globally distributed, while the distribution of AE is generally restricted to the northern hemisphere. In China, CE accounts for 75% of all echinococcosis cases. With rapid advances in surgical techniques in recent decades, the surgical strategy for CE has changed, especially with the continuous improvement of surgical methods and the expansion of surgical contraindications. To further understand the changes in surgical treatment strategies for hepatic CE, we interpreted and analyzed the existing literature addressing the surgical treatment of hepatic CE both domestically and abroad and briefly summarized them in chronological order. This review aims to provide a deeper understanding of the progress in the surgical treatment of hepatic CE to provide clearer avenues for its clinical diagnosis and treatment., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Citrate is a common primary metabolite which often characterizes fruit flavour. The key regulators of citrate accumulation in fruit and vegetables are poorly understood. We systematically analysed the dynamic profiles of organic acid components during the development of kiwifruit (Actinidia spp.). Citrate continuously accumulated so that it became the predominate contributor to total acidity at harvest. Based on a co-expression network analysis using different kiwifruit cultivars, an Al-ACTIVATED MALATE TRANSPORTER gene (AcALMT1) was identified as a candidate responsible for citrate accumulation. Electrophysiological assays using expression of this gene in Xenopus oocytes revealed that AcALMT1 functions as a citrate transporter. Additionally, transient overexpression of AcALMT1 in kiwifruit significantly increased citrate content, while tissues showing higher AcALMT1 expression accumulated more citrate. The expression of AcALMT1 was highly correlated with 17 transcription factor candidates. However, dual-luciferase and EMSA assays indicated that only the NAC transcription factor, AcNAC1, activated AcALMT1 expression via direct binding to its promoter. Targeted CRISPR-Cas9-induced mutagenesis of AcNAC1 in kiwifruit resulted in dramatic declines in citrate levels while malate and quinate levels were not substantially affected. Our findings show that transcriptional regulation of a major citrate transporter, by a NAC transcription factor, is responsible for citrate accumulation in kiwifruit, which has broad implications for other fruits and vegetables., (© 2023 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)