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Precise regulation of intracellular phosphate (Pi) is critical for cellular function, with xenotropic and polytropic retrovirus receptor 1 (XPR1) serving as the sole Pi exporter in humans. The mechanism of Pi efflux, activated by inositol pyrophosphates (PP-IPs), has remained unclear. This study presents cryo-electron microscopy structures of XPR1 in multiple conformations, revealing a transmembrane pathway for Pi export and a dual-binding activation pattern for PP-IPs. A canonical binding site is located at the dimeric interface of Syg1/Pho81/XPR1 (SPX) domains, and a second site, biased toward PP-IPs, is found between the transmembrane and SPX domains. By integrating structural studies with electrophysiological analyses, we characterized XPR1 as an inositol phosphates (IPs)/PP-IPs-activated phosphate channel. The interplay among its transmembrane domains, SPX domains, and IPs/PP-IPs orchestrates the conformational transition between its closed and open states.

The heterogeneity of endothelial cells (ECs) across human tissues remains incompletely inventoried. We constructed an atlas of > 210,000 ECs derived from 38 regions across 24 human tissues. Our analysis reveals significant differences in transcriptome, phenotype, metabolism and transcriptional regulation among ECs from various tissues. Notably, arterial, venous, and lymphatic ECs shared more common markers in multiple tissues than capillary ECs, which exhibited higher heterogeneity. This diversity in capillary ECs suggests their greater potential as targets for drug development. ECs from different tissues and vascular beds were found to be associated with specific diseases. Importantly, tissue specificity of EC senescence is more determined by somatic site than by tissue type (e.g. subcutaneus adipose tissue and visceral adipose tissue). Additionally, sex-specific differences in brain EC senescence were observed. Our EC atlas offers valuble resoursce for identifying EC subclusters in single-cell datasets from body tissues or organoids, facilitating the screen of tissue-specific targeted therapies, and serving as a powerful tool for future discoveries., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Cys-loop receptors are a large superfamily of pentameric ligand-gated ion channels with various physiological roles, especially in neurotransmission in the central nervous system. Among them, zinc-activated channel (ZAC) is a Zn 2+ -activated ion channel that is widely expressed in the human body and is conserved among eukaryotes. Due to its gating by extracellular Zn 2+ , ZAC has been considered a Zn 2+ sensor, but it has undergone minimal structural and functional characterization since its molecular cloning. Among the families in the Cys-loop receptor superfamily, only the structure of ZAC has yet to be determined. Here, we determined the cryo-EM structure of ZAC in the apo state and performed structure-based mutation analyses. We identified a few residues in the extracellular domain whose mutations had a mild impact on Zn 2+ sensitivity. The constriction site in the ion-conducting pore differs from the one in other Cys-loop receptor structures, and further mutational analysis identified a key residue that is important for ion selectivity. In summary, our work provides a structural framework for understanding the ion-conducting mechanism of ZAC., Competing Interests: Competing interests statement:The authors declare no competing interest.

Reproducing neural functions with artificial nanofluidic systems has long been an aspirational goal for neuromorphic computing. In this study, neural functions, such as neural activation and synaptic plasticity, are successfully accomplished with a polarity-switchable nanofluidic memristor (PSNM), which is based on the anodized aluminum oxide (AAO) nanochannel array. The PSNM has unipolar memristive behavior at high electrolyte concentrations and bipolar memristive behavior at low electrolyte concentrations, which can emulate neural activation and synaptic plasticity, respectively. The mechanisms for the unipolar and bipolar memristive behaviors are related to the polyelectrolytic Wien (PEW) effect and ion accumulation/depletion effect, respectively. These findings are beneficial to the advancement of neuromorphic computing on nanofluidic platforms.

Chronic stress leads to social avoidance and anhedonia in susceptible individuals, a phenomenon that has been observed in both human and animal models. Nevertheless, the underlying molecular mechanisms underpinning stress susceptibility and resilience remain largely unclear. There is growing evidence that epigenetic histone deacetylase (HDAC) mediated histone acetylation is involved in the modulation of depressive-related behaviors. We hypothesized that histone deacetylase 5 (HDAC5), which is associated with stress-related behaviors and antidepressant response, may play a vital role in the susceptibility to chronic stress. In the current study, we detected the levels of HDAC5 and acetylation of histone 4 (H4) in the hippocampus subsequent to chronic social defeat stress (CSDS) in C57BL/6J mice. We found that CSDS induces a notable increase in HDAC5 expression, concomitant with a reduction in the acetylation of histone H4 at lysine 12 (H4K12) in the hippocampus of susceptible mice. Meanwhile, intrahippocampal infusion of HDAC5 shRNA or HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) both reversed the depression susceptibility in susceptible mice that subjected to CSDS. Furthermore, HDAC5 overexpression was sufficient to induce depression susceptibility following microdefeat stress, accompanied by a significant reduction in H4K12 level within the hippocampus of mice. Additionally, the Morris water maze (MWM) results indicated that neither CSDS nor HDAC5 exerted significant effects on spatial memory function in mice. Taken together, these investigations indicated that HDAC5-modulated histone acetylation is implicated in regulating the depression susceptibility, and may be serve as potential preventive targets for susceptible individuals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Flutriafol, a globally utilized triazole fungicide in agriculture, is typically applied as a racemic mixture, but its enantiomers differ in bioactivity and environmental impact. The synthesis of flutriafol enantiomers is critically dependent on chiral precursors: 2,2-bisaryl-substituted oxirane [(2-fluorophenyl)-2-(4-fluorophenyl)oxirane, 1a ] and 1,2-diol [1-(2-fluorophenyl)-1-(4-fluorophenyl)ethane-1,2-diol, 1b ]. Here, we engineered a Rhodotorula paludigensis epoxide hydrolase ( Rp EH), obtaining mutant Escherichia coli / Rpeh H336W/L360F with a 6.4-fold enhanced enantiomeric ratio ( E ) from 5.5 to 35.4. This enabled a gram-scale resolution of rac - 1a by E. coli / Rpeh H336W/L360F , producing ( S )- 1a (98.2% ee s ) and ( R )- 1b (75.0% ee p ) with 44.3 and 55.7% analytical yields, respectively. As follows, chiral ( S )-flutriafol (98.2% ee ) and ( R )-flutriafol (75.0% ee ) were easily synthesized by a one-step chemocatalytic process from ( S )- 1a and a two-step chemocatalytic process from ( R )- 1b , respectively. This chemoenzymatic approach offers a superior alternative for the asymmetric synthesis of flutriafol enantiomers. Furthermore, molecular dynamics simulations revealed insight into the enantioselectivity improvement of Rp EH toward bulky 2,2-bisaryl-substituted oxirane 1a .

Due to their complex pathological mechanisms, neurodegenerative diseases have brought great challenges to drug development and clinical treatment. Studies have shown that many traditional Chinese medicines have neuroprotective pharmacological activities such as anti-inflammatory and anti-oxidation properties and have certain effects on improving the symptoms of neurodegenerative diseases and delaying disease progression. Flavonoids are the main active components of many traditional Chinese medicines for the treatment of neurodegenerative diseases. These compounds have a wide range of biological activities, including anti-inflammatory, anti-oxidative stress, regulation of autophagy balance, inhibition of apoptosis, and promotion of neuronal regeneration. This paper focuses on the neuroprotective effects of six common flavonoids: quercetin, rutin, luteolin, kaempferol, baicalein, and puerarin. It then systematically reviews their characteristics, mechanisms, and key signaling pathways, summarizes the common characteristics and laws of their neuroprotective effects, and discusses the significance of strengthening the research on the neuroprotective effects of these compounds, aiming to provide reference for more research and drug development of these substances as neuroprotective drugs.

The random flap is one of the commonly used techniques for tissue defect repair in surgery and orthopaedics, however the risk of ischaemic necrosis at the distal end of the flap limits its size and clinical application. Metformin (Met) is a first-line medication in the treatment of type 2 diabetes, with additional effects such as anti-tumor, anti-aging, and neuroprotective properties. In this study, we aimed to investigate the biological effects and potential mechanisms of Met in improving the survival of random skin flaps. Twenty-four male Sprague-Dawley rats and 12 male C57BL/6J mice underwent McFarlane flap surgery and divided into control (Ctrl) and Met groups (100 mg/kg). The survival rate of the flap were evaluated on day 7. Angiography, Laser doppler blood flow imaging, and H&E staining were used to assess blood flow supply and the levels of microvascular density. Then, reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured by test kits. Immunohistochemistry analysis was conducted to evaluate the expression of Vascular Endothelial Growth Factor A (VEGFA), Vascular endothelial cadherin (VE-cadherin) and CD31. Rats and mice in the Met group exhibited higher flap survival rate, microcirculatory flow, and higher expression levels of VEGFA and VE-cadherin compared with the Ctrl group. In addition, the level of oxidative stress was significantly lower in the met group. And then we demonstrated that the human umbilical vein endothelial cells (HUVECs) treated with Met can alleviate tert-butyl hydroperoxide (TBHP)-stimulated cellular dysfunction and oxidative stress injury. Mechanistically, Met markedly stimulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), and promoted Nrf2 nuclear translocation. Silencing of Nrf2 partially abolished the antioxidant and therapeutic effects of Met. In summary, our data have confirmed that Met has a positive effect on flap survival and reduces necrosis. The mechanism of action involves the regulation of the Nrf2/HO-1 signaling pathway to combat oxidative stress and reduce damage., 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.)

Patchouli (Pogostemon cablin (Blanco) Benth) is an important medicinal and aromatic plant widely cultivated in China, India, and other Southeast Asian countries. It is renowned for its diverse applications in traditional medicine and its detoxification, antibacterial, anti-inflammatory, and other pharmacological properties (Wu et al. 2016; Fang et al. 2022). In May 2023, a severe leaf spot disease was observed on Pogostemon cablin plants grown in most plantations in Yulin, Guangxi, China (22°26'N; 109°83'E), with over 50% incidence rate. Symptoms began as small, circular, brown spots on leaves, enlarging with yellow halos. Lesions expanded into irregular shapes with necrotic centers. Advanced stages showed extensive yellowing, browning, and leaf senescence. A total of 20 symptomatic plants were sampled from 5 different locations within the detected area, with 4 plants sampled per location. To isolate the pathogen, 20 affected leaves were collected from these plants and preliminarily washed with sterile distilled water (SDW). Five small tissue pieces (5×5 mm) were excised from the lesion edge of each leaf, surface-disinfected with 75% ethanol and 1% NaClO, rinsed thrice with SDW, and placed on potato dextrose agar (PDA) at 28 °C in darkness for 7 days. Out of these, 18 plants (90%) yield fungal isolate with recurrent and similar morphological characteristics. Four representative isolates (X5-1-1, X5-1-3, X5-1-5, and X5-1-7) were selected for further analysis. On PDA, colonies were initially white, gradually turning black on the surface, with light yellow on the reverse side of the plate. Conidia were brown to black, globose, rough-walled, and 2.6 to 5.2 µm in diameter. Conidial heads were brown-black, and conidiophores were smooth and hyaline. Morphological characteristics matched those of Aspergillus sp. (Guo et al. 2017). For molecular identification, the internal transcribed spacer (ITS) region and the β-tubulin (TUB) gene of all four isolates were sequenced (Lim et al. 2019). All four isolates (X5-1-1, X5-1-3, X5-1-5, and X5-1-7) showed consistent morphological characteristics and 100% identical ITS and TUB sequences. Representative sequences from isolate X5-1-5 were submitted to GenBank (ITS: PP789632; TUB: PP798205). The obtained ITS and TUB sequences showed 99% similarity to Aspergillus tubingensis (ITS: OP737633; TUB: MG991377). Based on morphological and molecular analyses, the fungus was identified as A. tubingensis (Palmer et al. 2019). For pathogenicity tests, a spore suspension (1 × 10^6 conidia/mL) was prepared from 7-day-old cultures of A. tubingensis grown on PDA. The suspension was sprayed onto leaves of 10 healthy Pogostemon cablin plants until runoff. Control plants were sprayed with SDW. All plants were kept in a controlled greenhouse (12/12h light/dark, 25 ± 2 °C, 90% humidity). After 7 d, symptoms identical to those observed in the field developed on all pathogen inoculated plants, while control plants remained asymptomatic. The fungus was successfully re-isolated from infected leaves in three successive trials, fulfilling Koch's postulates. Notably, A. tubingensis has previously been reported causing field diseases on strawberry in California, Jatropha curcas and Helleborus species in China (Palmer et al. 2019; Guo et al. 2017, Liaquat et al. 2019), and vine canker on table grape in Italy (Vitale et al. 2012). To our knowledge, this is the first report of A. tubingensis causing leaf spot on Pogostemon cablin in China. This finding provides a foundation for further investigate into the biology, epidemiology, and management of this disease.

Background: Dentatorubral-pallidoluysian atrophy is a rare autosomal dominant neurodegenerative disease. It is a rare disease in the world. Therefore, sharing clinical encounters of this case can deepen global awareness and understanding of the disease., Case Presentation: The patient was a 34-year-old male of Han nationality who was unmarried. The patient was admitted owing to weakness of the left lower limb with walking instability for 2 months and aggravation for 1 month. There was no dizziness, headache, numbness of limbs, convulsions, nausea, vomiting, abdominal pain, ataxia, nausea, vomiting, or abdominal pain. No nausea, vomiting, diarrhea, abdominal distension, tinnitus, hearing loss, fever, cough, expectoration. Personal history: worked in Cambodia 5 years ago, worked in Dubai 3 years ago, engaged in computer work, smoking or drinking habits. The patient was unmarried. Family history: the mother had symptoms similar to walking unsteadily (undiagnosed). Positive signs include a wide-base gait with a rotatory nystagmus that jumps upward in both eyes. Bilateral finger-nose instability test was quasi-positive, rapid alternating test was negative, and eye closure tolerance test was positive. Tendon reflexes were active in both upper limbs and hyperreflexia in both lower limbs. Stability of the heel, knee, and tibia. Genetic testing showed that the number of repeats in the dentatorubral-pallidoluysian atrophy ATN1 gene was 18 and 62, and the (CAG)n repeat sequence in the ATN1 gene was abnormal, with a repeat number of 62, and the patient was a pathogenic variant. The patient was diagnosed with dentatorubral-pallidoluysian atrophy. Dentatorubral-pallidoluysian atrophy remains a progressive neurodegenerative disease with no effective treatment. At present, the proband is taking 5 mg of buspirone three times a day, which has been reported to improve the symptoms. The patient was followed up for 6 months after taking buspirone, and there was no significant improvement in the temporary symptoms. At present, there are few cases of dentatorubral-pallidoluysian atrophy, and the characteristics of nystagmus in this disease have not been proposed in the past. This case reported the unusual presentation of nystagmus., Conclusion: Dentatorubral-pallidoluygur atrophy is a rare neurodegenerative disease with autosomal dominant inheritance. To the best of our knowledge, our present case report is the first case report of dentatorubral-pallidoluygur atrophy with specific nystagmus. We describe the special eye shake and its positive signs to increase dentatorubral-pallidoluysian atrophy clinical positive signs., (© 2024. The Author(s).)

Pheochromocytoma is a neuroendocrine tumor for which surgical resection is the main treatment.Malignant pheochromocytoma is very rare. Here,we present a case of adrenal pheochromocytoma invading the ureteral wall muscle layer, which resulted in left adrenal and left nephrectomy., (© 2024 The Authors.)

P2X receptors, a subfamily of ligand-gated ion channels activated by extracellular ATP, are implicated in various physiopathological processes, including inflammation, pain perception, and immune and respiratory regulations. Structural determinations using crystallography and cryo-EM have revealed that the extracellular three-dimensional architectures of different P2X subtypes across various species are remarkably identical, greatly advancing our understanding of P2X activation mechanisms. However, structural studies yield paradoxical architectures of the intracellular domain (ICD) of different subtypes (e.g., P2X3 and P2X7) at the apo state, and the role of the ICD in P2X functional regulation remains unclear. Here, we propose that the P2X3 receptor's ICD has an apo state conformation similar to the open state but with a less tense architecture, containing allosteric sites that influence P2X3's physiological and pathological roles. Using covalent occupancy, engineered disulfide bonds and voltage-clamp fluorometry, we suggested that the ICD can undergo coordinated motions with the transmembrane domain of P2X3, thereby facilitating channel activation. Additionally, we identified a novel P2X3 enhancer, PSFL77, and uncovered its potential allosteric site located in the 1α3β domain of the ICD. PSFL77 modulated pain perception in P2rx3 +/+ , but not in P2rx3 -/- , mice, indicating that the 1α3β, a "tunable" region implicated in the regulation of P2X3 functions. Thus, when P2X3 is in its apo state, its ICD architecture is fairly ordered rather than an unstructured outward folding, enabling allosteric modulation of the signaling of P2X3 receptors., (© 2024. The Author(s).)

In this study, the correlation between protein phosphorylation and deterioration in the quality of tilapia during storage in ice was examined by assessing changes in texture, water-holding capacity (WHC), and biochemical characteristics of myofibrillar protein throughout 7 days of storage. The hardness significantly decreased from 471.50 to 252.17 g, whereas cooking and drip losses significantly increased from 26.5% to 32.6% and 2.9% to 9.1%, respectively (P < 0.05). Myofibril fragmentation increased, while myofibrillar protein sulfhydryl content and Ca 2+ -ATPase activity decreased from 119.33 to 89.29 μmol/g prot and 0.85 to 0.46 μmolPi/mg prot/h, respectively (P < 0.05). Correlation analysis revealed that the myofibrillar protein phosphorylation level was positively correlated with hardness and Ca 2+ -ATPase activity but negatively correlated with WHC. Myofibrillar protein phosphorylation affects muscle contraction by influencing the dissociation of actomyosin, thereby regulating hardness and WHC. This study provides novel insights for the establishment of quality control strategies for tilapia storage based on protein phosphorylation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Seven unreported compounds were isolated from dried flower buds of Ochrocarpus longifolius in this study, including an alkaloid ochrocaracid A (1), five coumarins ochrocarpins I (2), J (3), K (4), L (5), and M (6), and one styryl-2-pyranone compound iresinoacid (7) and nine known compounds (8-16). All these compounds were found in O. longifolius for the first time. Their structural elucidation was achieved through NMR, HR-ESI-MS, and ECD data. Additionally, a glucose uptake-promoting activity assay revealed that compounds 10 (128.21 μM) and 16 (123.15 μM) increased the glucose uptake capacity of L6 cells by 1.49-fold and 1.48-fold, respectively. These bioactive compounds could be potential candidates for further pharmaceutical applications., 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.)

The prominent role of the P-element induced wimpy testis (PIWI)-interacting RNA (piRNA) pathway in animals is to silence transposable elements and maintain genome stability, ensuring proper gametogenesis in gonads. GASZ (Germ cell protein with Ankyrin repeats, Sterile alpha motif, and leucine Zipper) is an evolutionarily conserved protein located on the outer mitochondrial membrane of germ cells and plays vital roles in the piRNA pathway and spermatogenesis in mammals. In the model insect Drosophila melanogaster, GASZ is essential for piRNA biogenesis and oogenesis, whereas its biological functions in non-drosophilid insects are still unknown. Here, we describe a comprehensive investigation of GASZ functions in the silkworm, Bombyx mori, a lepidopteran model insect, by using a binary transgenic CRISPR/Cas9 system. The BmGASZ mutation did not affect growth and development, but led to sterility in both males and females. Eupyrene sperm bundles of mutant males exhibited developmental defects, while the apyrene sperm bundles were normal, which were further confirmed through double copulation experiments with sex-lethal mutants, which males possess functional eupyrene sperm and abnormal apyrene sperm. In female mutant moths, ovarioles were severely degenerated and the eggs in ovarioles were deformed compared with that of wild type (WT). Further RNA-seq and RT-qPCR analysis revealed that amounts of piRNAs and transposon expression were dysregulated in gonads of mutants. In summary, this study has demonstrated vital roles of BmGASZ in gametogenesis through regulating the piRNA pathway in B. mori., (© 2024 Royal Entomological Society.)

Various isothermal amplification methods have been developed for point-of-care testing (POCT) of various infectious diseases. Here, we proposed a novel isothermal amplification method, named as 5'-half complementary primers mediated isothermal amplification (HCPA). Because of the similarity of our method to the previous method competitive annealing mediated isothermal amplification (CAMP) in primer design, we also use the name CAMP for our method. We demonstrated that CAMP is mediated by both a linear isothermal amplification pattern and a loop-mediated isothermal amplification pattern. To improve the specificity and enable multiplex detection, we further developed HiFi-CAMP method that uses a small amount of high-fidelity DNA polymerase to cut HFman probe to release fluorescent signal. The HiFi-CAMP method was demonstrated to have a good specificity and sensitivity, and fast amplification speed in detection of three human respiratory viruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory syncytial virus A (RSV-A) and influenza A viruses (IAV). When compared with gold standard RT-qPCR assays, the HiFi-CAMP assays showed sensitivities of 90.0 %, 71.4 % and 78.1 %, specificities of 100 %, 100 % and 95.5 %, and consistencies of 93.0 %, 93.3 % and 88.2 % for SARS-CoV-2, RSV-A and IAV, respectively. Furthermore, a duplex HiFi-CAMP assay was also developed to simultaneously detect RSV-A and SARS-CoV-2. The HiFi-CAMP will provide a promising candidate for POCT diagnosis in resource-limited settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study aimed to explore the impact of the COVID-19 pandemic on non-suicidal self-injury (NSSI) among youth students, and the mediating role of psychological factors in the relationship between the COVID-19 pandemic and NSSI., Method: An online survey was conducted at junior and senior high schools, as well as universities located in Jingzhou, Hubei Province, China between June 2021 and January 2022. The COVID-19 Impact Index was constructed using multiple correspondence analysis (MCA) method. The bootstrapping method was used for mediation analysis., Results: A total of 16025 youth participated in the study and 12507 youth (78.1%) finished the questionnaires. The COVID-19 Impact Index had a significantly positive effect on NSSI (r=0.16, p<0.001). The mediation analysis results showed that the COVID-19 Impact Index had a significant indirect effect on youth' NSSI (β=0.0918, 95% CI [0.0788, 0.1048]), and this indirect effect was mainly achieved through affecting youth' anxiety, depression and post-traumatic stress disorder (PTSD). The mediation effect of anxiety on NSSI was 0.0584, the direct effect was 0.0334, and the mediation proportion was 63.6%. The mediation effect of depression on NSSI was 0.0668, the direct effect was 0.0250, and the mediation proportion was 72.8%. The mediation effect of PTSD on NSSI was 0.0640, the direct effect was 0.0278, and the mediation proportion was 69.7%. All the mediation effects, direct effects and total effects were statistically significant (p<0.001)., Conclusion: The higher the impact of the COVID-19 Impact Index, the higher the prevalence of NSSI among youth students. Anxiety, depression and PTSD had mediated the relationship between the COVID-19 Impact Index and NSSI. It is suggested that specific health policies, mental health services and interventions should be developed to reduce the NSSI and improve mental health status among youth students during the COVID-19 pandemic., 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 Zhou, Yu, Liu, Zhou, Sheng, Zhang, Deng and Ran.)

Knee osteoarthritis (OA), characterized by multiple joint tissue degenerations, remains a significant clinical challenge. Recent evidence suggests that crosstalk within the osteochondral unit may drive OA progression. Although structural-biomechanical properties of bone and cartilage have been studied, potential interaction within the osteochondral unit in the context of OA has yet to be investigated. We performed comprehensive structural and biomechanical quantification of the cartilage, subchondral bone plate (SBP), and subchondral trabecular bone (STB) using 101 osteochondral cores collected from tibial plateaus of 12 control human cadavers (CT, 5 male/7 female) and 19 patients undergoing total knee replacement (OA, 6 male/13 female). For each sample, we quantified SBP microstructure, plate-and-rod morphological properties of the STB using individual trabecula segmentation, and morphological and compositional properties of the articular cartilage. We also performed indentation testing on each compartment of the osteochondral unit to extract the respective structural-mechanical properties. Cartilage thickness was lower in moderate and severe OA regions, while Osteoarthritis Research Society International score was higher only in severe OA regions. GAG content did not change in any OA region. Aggregate and shear moduli were lower only in severe OA regions, while permeability was lower only in moderate OA regions. In the SBP, thickness and tissue mineral density were higher in moderate and severe OA regions. Tissue modulus of STB was lower in moderate OA regions despite a thicker and more mineralized SBP; this deterioration was not observed in severe OA regions. Regression analysis revealed strong correlations between cartilage and STB properties in CT; these correlations were also found in moderate OA regions but were not observed in severe OA regions. In summary, our findings comprehensively characterize the human OA osteochondral unit. Importantly, uncoupling cartilage and subchondral bone structural-mechanical properties may be a hallmark of OA., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Millettia speciosa Champ, renowned for its diverse applications in traditional medicine, is extensively cultivated in the Guangxi region of China, spanning roughly 5,973 hectares. In July 2021, a plantation in Yulin, Guangxi, China (22°64'N; 110°29'E), exhibited severe leaf spot disease on M. speciosa. Notably, a 46,690 square meters area had over 40% leaf spot incidence. Initially, symptoms appeared as small, circular, pale-yellow lesions on the leaves, then turned into irregular, dark brown spots with yellow halos, leading to the wilt and defoliation of leaves. To identify the responsible pathogen, a total of five symptomatic leaves were collected and sterilized systematically. Small tissue segments (5×5 mm) from lesion peripheries were aseptically excised, then surface sterilized with 75% ethanol for 10 s, and 1% sodium hypochlorite (NaClO) for 3 min. Following this, the sterilized tissues were triple-rinsed with sterile water and cultured on potato dextrose agar (PDA) at 28 °C in the dark for 7 d. A total of seven isolates were obtained through single-spore isolation, and one representative isolate, N2-3, was selected for further analysis. After 7 d of incubation, colonies displayed flat, white, and extensively branched aerial hyphae. Over time, the reverse side of the colony changed from white to yellowish-white. The pycnidia were black with conidial droplets ranging from cream to pale yellow exuding from their ostioles. The α-conidia were one-celled, hyaline, ovoid to cylindrical, typically with one or two droplets, 2.6 to 5.9 ×1.4 to 3.9 μm (n=50). These morphological traits align with those of the genus Diaporthe, as reported by Li et al. (2022) and Crous et al. (2015). To identify the species, isolate N2-3 underwent sequencing of the internal transcribed spacer (ITS), β-tubulin (BT), and translation elongation factor 1 alpha (EF1-α) sections (Huang et al. 2021). Obtained sequences of ITS, BT and EF1-α (Genebank accessions nos. OR600532, OR662169 and OR662168) displayed a 99% similarity to Diaporthe tulliensis (Genebank accessions nos. OP219651, ON932382, OL412437, respectively). Based on the concatenated ITS, BT and EF1-α, a neighbor-joining phylogenetic analyses using MEGA7.0 clustered with D. tulliensis. Therefore, the fungus was identified as D. tulliensis (teleomorph name) based on morphological and molecular features. A pathogenicity test was conducted on 1-year-old M. speciosa seedlings by gently abrading healthy leaves with sterilized toothpicks to create superficial wounds. Wounded leaves were then inoculated with 5 mm diameter mycelial plugs, while control seedlings received PDA plugs. Three leaves per plant and five plants per treatment were selected for assessment. All seedlings were kept in a controlled greenhouse (12/12h light/dark, 25 ± 2 °C, 90% humidity). After 7 d, the inoculated leaves showed symptoms like those in the field, while control plants remained healthy. The fungus was consistently reisolated from the infected leaves, satisfying Koch's postulates. Notably, D. tulliensis has caused Boston ivy leaf spot, bodhi tree leaf spot, cacao pod rot, and jasmine stem canker (Huang et al. 2021; Li et al. 2022; Serrato-Diaz et al. 2022; Hsu et al. 2023). This discovery is significant as it marks the first report of Diaporthe tulliensis causing leaf spot on Millettia speciossa in China, which has direct implications for the development of diagnostic tools and research into potential disease management strategies.

Star anise (Illicium verum), a valuable spice tree, faces significant threats from fungal diseases, particularly Alternaria leaf spot. This study investigates the potential of a soil-derived actinomycete strain, YG-5, as a biocontrol agent against Alternaria tenuissima, the causative pathogen on Alternaria leaf spot in star anise. Through comprehensive morphology, physiology, biochemistry, and genetic analyses, we identified the isolate as Streptomyces sp. YG-5. The strain exhibited broad-spectrum antimicrobial activity against several plant pathogens, with inhibition rates ranging between 36.47 to 80.34%. We systematically optimized the fermentation conditions for YG-5, including medium composition and cultivation parameters. The optimized process resulted in an 89.56% inhibition rate against A. tenuissima, a 14.72% improvement over non-optimized conditions. Notably, the antimicrobial compounds produced by YG-5 demonstrated stability across various temperatures, pH levels, and UV irradiation. In vivo efficacy trials showed promising results, with YG-5 fermentation broth reducing Alternaria leaf spot incidence on star anise leaves by 56.95%. These findings suggest that Streptomyces sp. YG-5 holds significant potential as a biocontrol agent against Alternaria leaf spot in star anise cultivation, offering a sustainable approach to disease management in this valuable crop., (© 2024. The Author(s).)

The acoustic black hole (ABH) structure exhibits remarkable energy focalization above a given cut-on frequency, offering potential for broadband vibration suppression in structures. However, its energy focusing properties diminish significantly below this cut-on frequency. Therefore, it is crucial to enhance the vibration attenuation capabilities of ABH structures within the low frequency range. This study presents a numerical investigation into the impact of thin-walled structures with embedded ABHs and distributed dynamic vibration absorbers (DVAs) on low frequency broadband vibration reduction. Initially, the focusing characteristics of the ABH thin-walled structure is analyzed, aiding in the attached position of DVAs. Furthermore, the influence of the design parameters and attached position of DVA on the broadband damping effect of the structure is explored. The findings indicate that DVAs designed for low frequencies can achieve significant vibration attenuation across the entire frequency spectrum, including low frequencies, when installed at specific focusing positions. When compared to the position with the maximum vibration response, while the attenuation of the low frequency common amplitude value is slightly reduced, greater vibration attenuation across the entire frequency band is achieved. This research offers valuable insights into optimizing the integration of DVAs with ABHs in thin-walled structures for enhanced broadband vibration attenuation., (© 2024. The Author(s).)

The diversity of cell types in the brain and how these change during different developmental stages, remains largely unknown. The life cycle of insects is short and goes through 4 distinct stages including embryonic, larval, pupal, and adult stages. During postembryonic life, the larval brain transforms into a mature adult version after metamorphosis. The silkworm, Bombyx mori, is a lepidopteran model insect. Here, we characterized the brain cell repertoire of larval and adult B. mori by obtaining 50 708 single-cell transcriptomes. Seventeen and 12 cell clusters from larval and adult brains were assigned based on marker genes, respectively. Identified cell types include Kenyon cells, optic lobe cells, monoaminergic neurons, surface glia, and astrocyte glia. We further assessed the cell type compositions of larval and adult brains. We found that the transition from larva to adult resulted in great expansion of glial cells. The glial cell accounted for 49.8% of adult midbrain cells. Compared to flies and ants, the mushroom body kenyon cell is insufficient in B. mori, which accounts for 5.4% and 3.6% in larval and adult brains, respectively. Analysis of neuropeptide expression showed that the abundance and specificity of expression varied among individual neuropeptides. Intriguingly, we found that ion transport peptide was specifically expressed in glial cells of larval and adult brains. The cell atlas dataset provides an important resource to explore cell diversity, neural circuits and genetic profiles., (© 2023 Institute of Zoology, Chinese Academy of Sciences.)

Objective: To explore the overall survival and prognostic factors of patients over 50 years old with acute myeloid leukemia (AML)., Methods: The clinical data of 222 AML patients aged over 50 years in our hospital from January 2016 and June 2021 were retrospectively analyzed. Kaplan-Meier method was used to evaluate the overall survival (OS) rate, and Cox regression model to evaluate the prognostic factors., Results: The 1-year and 3-year OS rates of all patients were 46.8% and 28.8%, respectively. The recurrence rate of patients who achieved remission during follow-up time was 57%. Both univariate and multivariate analysis showed that advanced age, MLL family fusion gene, PHF6 gene mutation, TP53 gene mutation, intolerance to standard chemotherapy, incomplete remission, complex karyotype, +mar karyotype and inv(3) karyotype were significantly correlated with prognosis (all P <0.05). Negative fusion gene and positive AML- ETO fusion gene had no obvious survival advantage in this population. In patients with complete remission, there was no significant survival advantage in those who achieved minimal residual disease negative., Conclusion: AML patients aged over 50 years have a poor outcome and high recurrence rate. The prognosis is affected by multiple factors and has its own characteristics.

Styrax japonicus is a medicinal and ornamental shrub belonging to the Styracaceae family. To explore the diversity and characteristics of the chloroplast genome of S. japonicus , we conducted sequencing and comparison of the chloroplast genomes of four naturally distributed S. japonicus . The results demonstrated that the four chloroplast genomes (157,914-157,962 bp) exhibited a typical quadripartite structure consisting of a large single copy (LSC) region, a small single copy (SSC) region, and a pair of reverse repeats (IRa and IRb), and the structure was highly conserved. DNA polymorphism analysis revealed that three coding genes ( infA , psbK , and rpl33 ) and five intergene regions ( petA - psbJ , trnC - petN , trnD - trnY , trnE - trnT , and trnY - trnE ) were identified as mutation hotspots. These genetic fragments have the potential to be utilized as DNA barcodes for future identification purposes. When comparing the boundary genes, a small contraction was observed in the IR region of four S. japonicus . Selection pressure analysis indicated positive selection for ycf1 and ndhD . These findings collectively suggest the adaptive evolution of S. japonicus . The phylogenetic structure revealed conflicting relationships among several S. japonicus , indicating divergent evolutionary paths within this species. Our study concludes by uncovering the genetic traits of the chloroplast genome in the differentiation of S. japonicus variety, offering fresh perspectives on the evolutionary lineage of this species.

To explore the mutagenic effect of the space environment on Pueraria montana and select the elite germplasm with good growth conditions and high isoflavone content, this study observed the agronomic traits, determined the flower isoflavone content, and labeled amplified fragment length polymorphism(AFLP) fluorescent molecular markers of 79 P. montana plants exposed to space mutagenesis(SP1 group) and 10 control plants of P. montana(CK group). Excel 2019, SPSS 25.0, NTSYSpc-2.11F, and Popgen 32 were employed to analyze the genetic diversity and perform the cluster analysis. The results showed that the SP1 group presented changed leaf hairy attitude and flower structure and higher CV and H' of quantitative traits than the CK group. The cluster analysis screened out five plants in the SP1 group. Ten P. montana plants in the SP1 group had higher content of 6″-O-xylosyl-tectoridin and tectoridin in the flowers than the control group, with the total content of both exceeding 11%. After clustering, 9 plants in the SP1 group were separated. Nine pairs of polymorphic primers were screened out frrom 64 pairs of primers. A total of 1 620 polymorphic loci were detected, with the average percentage of polymorphic loci(PPL) of 83.33%. The average Nei's gene diversity index(H) and Shannon's information index(I) were 0.192 2 and 0.305 2, respectively. After clustering, 4 plants in the SP1 group were screened out. According to the above results, plants No. 30, No. 66, and No. 89 in the SP1 group were subjected to greater mutagenic effect by the space environment and presented better growth and higher flower isoflavone content. Moreover, plant No. 30 showed the flower structure variation and flower weight two times of that in the CK group. These plants can be used as key materials for the subsequent experiments.

Environmental lipids are essential for fueling tumor energetics, but whether these exogenous lipids transported into cancer cells facilitate immune escape remains unclear. Here, we find that CD36, a transporter for exogenous lipids, promotes acute myeloid leukemia (AML) immune evasion. We show that, separately from its established role in lipid oxidation, CD36 on AML cells senses oxidized low-density lipoprotein (OxLDL) to prime the TLR4-LYN-MYD88-nuclear factor κB (NF-κB) pathway, and exogenous palmitate transfer via CD36 further potentiates this innate immune pathway by supporting ZDHHC6-mediated MYD88 palmitoylation. Subsequently, NF-κB drives the expression of immunosuppressive genes that inhibit anti-tumor T cell responses. Notably, high-fat-diet or hypomethylating agent decitabine treatment boosts the immunosuppressive potential of AML cells by hijacking CD36-dependent innate immune signaling, leading to a dampened therapeutic effect. This work is of translational interest because lipid restriction by US Food and Drug Administration (FDA)-approved lipid-lowering statin drugs improves the efficacy of decitabine therapy by weakening leukemic CD36-mediated immunosuppression., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Nanhaia speciosa, commonly known as Niudali, is a medicinal woody vine belonging to the Leguminosae family. Valued for its culinary and medicinal properties, it is extensively cultivated, covering approximately 5,973 hm2 in the Guangxi Zhuang Autonomous Region of China. The edible tubers of this plant are reported to possess antibacterial and antioxidant effects (Luo et al., 2023; Shu et al., 2020). In July 2021, a Niudali plantation in Yulin, Guangxi, China (22°64'N; 110°29'E) exhibited leaf spot symptoms, with an incidence rate exceeding 40% across a 46,690 m2 area. Initially, small circular, pale yellow spots appeared on the leaves, which subsequently evolved into dark brown lesions surrounded by yellow halos, ultimately leading to foliage wilting. Leaves exhibiting typical symptoms were collected for pathogen investigation. The leaves were thoroughly washed with sterile water and small tissue fragments (5×5 mm) were excised from the lesion periphery. These fragments were surface-sterilized with 75% ethanol and 1% NaClO, rinsed three times with sterile water, and subsequently cultured on potato dextrose agar (PDA) at 28 °C in darkness for 7 days. Through single-spore isolation, seven isolates with similar morphological traits were obtained. After 7 days of incubation on PDA at 28 °C in dark, the colonies exhibited a white to grey coloration on the upper surface with abundant aerial hyphae, while the underside appeared dark black. The conidia, cylindrical or obclavate in shape, were straight, pale brown, and measured 30.1-128.9 μm × 4.8-15.0 μm (n=50). The morphological characteristics matched those of Corynespora sp.(Wang et al. 2021). For molecular identification, the isolate N5-2 underwent DNA sequence analysis using genomic DNA and primers ITS1/ITS4 and EF1-688F/EF1-1251R. The sequences (ITS: OP550425; TEF1-α: OQ117118) were deposited in GenBank, exhibiting 98% identity to C. cassiicola (OP981637) for TEF1-α and 99% homology to C. cassiicola (OP957070) for ITS. Based on the concatenated ITS and TEF1-α, a maximum likelihood phylogenetic analyses using MEGA7.0 clustered the isolate with C. cassiicola. Consequently, the fungus was identified as C. cassiicola based on its morphological and molecular features. In the pathogenicity test on 1-year-old Nanhaia speciosa seedlings, leaves were gently scratched and inoculated with mycelial plugs (5 mm). Control seedlings received PDA plugs. Five leaves per plant and five plants per treatment were selected for assessment. All seedling were maintained in a greenhouse (12/12h light/dark cycle, 25 ± 2°C, 90% humidity). After a 7-day incubation period, all leaves subjected to fungal inoculation exhibited symptoms consistent with those observed in the field, while control plants remained symptom-free. The fungus was successfully reisolated from the infected leaves in three successive trials, fulfilling Koch's postulates. While C. cassiicola is well-documented for inducing leaf spots on various plant species, including Jasminum nudiflorum, Strobilanthes cusia, Acanthus ilicifolius, Syringa species (Hu et al., 2023; Liu et al., 2023; Xie et al., 2021; Wang et al., 2021), this study represents the first report of C. cassiicola causing leaf spots on Nanhaia speciosa in China. The identification of this pathogen in Nanhaia speciosa has significant implications for future epidemiological investigations and serves as a valuable reference for controlling leaf spot disease in Nanhaia speciosa.

The disturbance of ecological stability may take place in tropical regions due to the elevated biomass density resulting from heavy metal and other contaminant pollution. In this study, 62 valid soil samples were collected from Sanya. Source analysis of heavy metals in the area was carried out using absolute principal component-multiple linear regression receptor modelling (APCS-MLR); the comprehensive ecological risk of the study area was assessed based on pollution sources; the Monte-Carlo model was used to accurately predict the health risk of pollution sources in the study area. The results showed that: The average contents of soil heavy metals Cu, Ni and Cd in Sanya were 5.53, 6.56 and 11.66 times higher than the background values of heavy metals. The results of soil geo-accumulation index (I geo ) showed that Cr, Mo, Mn and Zn were unpolluted to moderately polluted, Cu and Ni were moderately polluted, and Cd was moderately polluted to strongly polluted. The main sources of heavy metal pollution were natural sources (57.99%), agricultural sources (38.44%) and traffic sources (3.57%). Natural and agricultural sources were jointly identified as priority control pollution sources and Cd was the priority control pollution element for soil ecological risk. Heavy metal content in Sanya did not pose a non-carcinogenic risk to the population, but there was a carcinogenic risk to children. The element Zn had a high carcinogenic risk to children, and was a priority controlling pollutant element for the risk of human health, with agricultural sources as the priority controlling pollutant source., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Efforts on developing transient receptor potential vanilloid 1 (TRPV1) drugs for pain management have been hampered by deleterious hypo- or hyperthermia caused by TRPV1 agonists/antagonists. Here, we compared the effects of four antagonists on TRPV1 polymodal gating and core body temperature (CBT) in Trpv1 +/+ , Trpv1 -/- , and Trpv1 T634A/T634A . Neither the effect on proton gating nor drug administration route, hair coverage, CBT rhythmic fluctuations, or inflammation had any influence on the differential actions of TRPV1 drugs on CBT. We identified the S4-S5 linker region exposed to the vanilloid pocket of TRPV1 to be critical for hyperthermia associated with certain TRPV1 antagonists. PSFL2874, a TRPV1 antagonist we discovered, is effective against inflammatory pain but devoid of binding to the S4-S5 linker and inducing CBT changes. These findings implicate that biased allosteric mechanisms exist for TRPV1 coupling to nociception and CBT regulation, opening avenues for the development of non-opioid analgesics without affecting CBT., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In this experiment, the micro-precipitation method was used to prepare self-assembled nanoparticles of Herpetospermum caudigerum Wall.(MP-SAN). The process was optimized using average particle size and polydispersity index(PDI)as evaluation indexes. The mean particle size, PDI,zeta potential, and microstructure of MP-SAN were characterized. The intestinal absorption mechanism of dehydrodiconiferyl alcohol(DA)and herpetrione(Her)in MP-SAN was investigated through single-pass intestinal perfusion in rats. The optimized process parameters for producing MP-SAN were a stirring speed of 800 r·min~(-1),stirring time of 5 min, and rotary evaporation temperature of 40℃. The resulting MP-SAN exhibited a spherical-like structure and uniform morphology, with a mean particle size of(267.63±13.27) nm, a PDI of 0.062 0±0.043 9,and a zeta potential of(-46.18±3.66) mV. The absorption rate constant(K&#95;a)and apparent permeability coefficient(P&#95;(app))of DA in the ileal segment were significantly higher than those in the jejunal segment(P&lt;0.05). However, there was no significant difference in the absorption of Her between the ileal and jejunal segments. Intestinal absorption parameters of DA and Her tended to increase with increasing drug concentration. Specifically, the K&#95;a and P&#95;(app) of DA in MP-SAN in the high-concentration group were significantly higher than those in the low-concentration group(P&lt;0.01). The addition of verapamil, a P-glycoprotein inhibitor, did not significantly affect the intestinal absorption of DA and Her. However, the absorption of both DA and Her in MP-SAN was significantly increased by the addition of indomethacin(P&lt;0.05),suggesting that DA and Her may be substrates for multidrug resistance-associated protein 2.

This study compares the skin structures of Rana kukunoris with two different skin colors living in the same area of Haibei in the Northeastern Qinghai-Tibet Plateau. The skin thickness of the khaki R. kukunoris was significantly greater than that of the brown R. kukunoris (P < 0.01), and significantly more mucous and granular glands were present on the dorsal skin of the khaki frog (P < 0.05). Meanwhile, the melanocytes on the dorsal skin of the brown frog were significantly larger than those on the khaki one (P < 0.05). Morphological changes in the expansion and aggregation of melanocytes seemed to deepen the skin color of R. kukunoris. Moreover, transcriptome sequencing identified tyrosine metabolism, melanogenesis, and riboflavin metabolism as the main pathways involved in melanin formation and metabolism in brown R. kukunoris. TYR, MC1R was upregulated as the skin color of R. kukunoris was deepened and contributed to melanin production and metabolism. In contrast, the khaki frog had significantly more upregulated genes and metabolic pathways related to autoimmunity. The khaki frog appeared to defend against ultraviolet (UV) radiation-induced damage by secreting mucus and small molecular peptides, whereas the brown frog protected itself by distributing a large amount of melanin. Hence, the different skin colors of R. kukunoris might represent different adaptation strategies for survival in the intense UV radiation environment of the Qinghai-Tibet Plateau., 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.)

Objective: Little is known about the association between whole-blood nicotinamide adenine dinucleotide (NAD + ) levels and nabothian cysts. This study aimed to assess the association between NAD + levels and nabothian cysts in healthy Chinese women., Methods: Multivariate logistic regression analysis was performed to analyze the association between NAD + levels and nabothian cysts., Results: The mean age was 43.0 ± 11.5 years, and the mean level of NAD + was 31.3 ± 5.3 μmol/L. Nabothian cysts occurred in 184 (27.7%) participants, with single and multiple cysts in 100 (15.0%) and 84 (12.6%) participants, respectively. The total nabothian cyst prevalence gradually decreased from 37.4% to 21.6% from Q1 to Q4 of NAD + and the prevalence of single and multiple nabothian cysts also decreased across the NAD + quartiles. As compared with the highest NAD + quartile (≥ 34.4 μmol/L), the adjusted odds ratios with 95% confidence interval of the NAD + Q1 was 1.89 (1.14-3.14) for total nabothian cysts. The risk of total and single nabothian cysts linearly decreased with increasing NAD + levels, while the risk of multiple nabothian cysts decreased more rapidly at NAD + levels of 28.0 to 35.0 μmol/L., Conclusion: Low NAD + levels were associated with an increased risk of total and multiple nabothian cysts., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Background: The animal sperm shows high diversity in morphology, components, and motility. In the lepidopteran model insect, the silkworm Bombyx mori, two types of sperm, including nucleate fertile eupyrene sperm and anucleate unfertile apyrene sperm, are generated. Apyrene sperm assists fertilization by facilitating the migration of eupyrene spermatozoa from the bursa copulatrix to the spermatheca. During spermatogenesis, eupyrene sperm bundles extrude the cytoplasm by peristaltic squeezing, while the nuclei of the apyrene sperm bundles are discarded with the same process, forming matured sperm., Results: In this study, we describe that a mechanoreceptor BmPiezo, the sole Piezo ortholog in B. mori, plays key roles in larval feeding behavior and, more importantly, is essential for eupyrene spermatogenesis and male fertility. CRISPR/Cas9-mediated loss of BmPiezo function decreases larval appetite and subsequent body size and weight. Immunofluorescence analyses reveal that BmPiezo is intensely localized in the inflatable point of eupyrene sperm bundle induced by peristaltic squeezing. BmPiezo is also enriched in the middle region of apyrene sperm bundle before peristaltic squeezing. Cytological analyses of dimorphic sperm reveal developmental arrest of eupyrene sperm bundles in BmPiezo mutants, while the apyrene spermatogenesis is not affected. RNA-seq analysis and q-RT-PCR analyses demonstrate that eupyrene spermatogenic arrest is associated with the dysregulation of the actin cytoskeleton. Moreover, we show that the deformed eupyrene sperm bundles fail to migrate from the testes, resulting in male infertility due to the absence of eupyrene sperm in the bursa copulatrix and spermatheca., Conclusions: In conclusion, our studies thus uncover a new role for Piezo in regulating spermatogenesis and male fertility in insects., (© 2024. The Author(s).)

Fluorosis due to high fluoride levels in drinking water profoundly affects the development of human skeletal and dental structures. Sodium butyrate (NaB) has been found to regulate overall bone mass and prevent pathological bone loss. However, the mechanism of NaB action on fluorosis remains unclear. In this study, a rat model of fluorosis induced by 100 mg/L sodium fluoride was used to investigate the impact of NaB on bone homeostasis and serum metabolomics. It was found that NaB significantly reduced the levels of bone resorption markers CTX-Ⅰ and TRACP-5B in fluorosis rats. Moreover, NaB increased calcium and magnesium levels in bone, while decreasing phosphorus levels. In addition, NaB improved various bone microstructure parameters, including bone mineral density (BMD), trabecular thickness (Tb. Th), trabecular bone separation (Tb. SP), and structural model index (SMI) in the femur. Notably, NaB intervention also enhanced the antioxidant capacity of plasma in fluorosis rats. Furthermore, a comprehensive analysis of serum metabolomics by LC-MS revealed a significant reversal trend of seven biomarkers after the intervention of NaB. Finally, pathway enrichment analysis based on differential metabolites indicated that NaB exerted protective effects on fluorosis by modulating arginine and proline metabolic pathways. These findings suggest that NaB has a beneficial effect on fluorosis and can regulate bone homeostasis by ameliorating metabolic disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Apart from mediating viral entry, the function of the free HIV-1 envelope protein (gp120) has yet to be elucidated. Our group previously showed that EP2 derived from one β-strand in gp120 can form amyloid fibrils that increase HIV-1 infectivity. Importantly, gp120 contains ~30 β-strands. We examined whether gp120 might serve as a precursor protein for the proteolytic release of amyloidogenic fragments that form amyloid fibrils, thereby promoting viral infection. Peptide array scanning, enzyme degradation assays, and viral infection experiments in vitro confirmed that many β-stranded peptides derived from gp120 can indeed form amyloid fibrils that increase HIV-1 infectivity. These gp120-derived amyloidogenic peptides, or GAPs, which were confirmed to form amyloid fibrils, were termed gp120-derived enhancers of viral infection (GEVIs). GEVIs specifically capture HIV-1 virions and promote their attachment to target cells, thereby increasing HIV-1 infectivity. Different GAPs can cross-interact to form heterogeneous fibrils that retain the ability to increase HIV-1 infectivity. GEVIs even suppressed the antiviral activity of a panel of antiretroviral agents. Notably, endogenous GAPs and GEVIs were found in the lymphatic fluid, lymph nodes, and cerebrospinal fluid (CSF) of AIDS patients in vivo. Overall, gp120-derived amyloid fibrils might play a crucial role in the process of HIV-1 infectivity and thus represent novel targets for anti-HIV therapeutics., (© 2024. The Author(s), under exclusive licence to CSI and USTC.)

Consumers are increasing their daily demand for beef and are becoming more discerning about its nutritional quality and flavor. The present objective was to evaluate how the ration energy content (combined net energy, Nemf) impacts the slaughter performance, carcass characteristics, and meat qualities of Honghe yellow cattle raised in confinement. Fifteen male Honghe yellow cattle were divided into three groups based on a one-way design: a low-energy group (LEG, 3.72 MJ/kg), a medium-energy group (MEG, 4.52 MJ/kg), and a high-energy group (HEG, 5.32 MJ/kg). After a period of 70 days on these treatments, the animals were slaughtered and their slaughter performance was determined, and the longissimus dorsi muscle (LD) and biceps femoris (BF) muscles were gathered to evaluate meat quality and composition. Increasing the dietary energy concentration led to marked improvements ( p < 0.05) in the live weight before slaughter (LWBS), weight of carcass, backfat thickness, and loin muscle area. HEG also improved the yield of high-grade commercial cuts (13.47% vs. 10.39%) ( p < 0.05). However, meat quality traits were not affected by treatment except for shear force, which was affected by dietary energy. A significant improvement ( p < 0.05) in the intramuscular fat (IMF) content was observed in the HEG. Little effect on the amino acid profile was observed ( p > 0.05), except for a tendency ( p = 0.06) to increase the histidine concentration in the BF muscle. Increasing dietary energy also reduced C22:6n-3 and saturated fatty acids (SFAs) and enhanced C18:1 cis-9 and monounsaturated fatty acids (MUFAs, p < 0.05). Those results revealed that increasing energy levels of diets could enhance slaughter traits and affect the meat quality and fatty acid composition of different muscle tissues of Honghe yellow cattle. These results contribute to the theoretical foundation to formulate nutritional standards and design feed formulas for the Honghe yellow cattle.

P2X receptors are extracellular ATP-gated ion channels that form homo- or heterotrimers and consist of seven subtypes. They are expressed in various tissues, including neuronal and nonneuronal cells, and play critical roles in physiological processes such as neurotransmission, inflammation, pain, and cancer. As a result, P2X receptors have attracted considerable interest as drug targets, and various competitive inhibitors have been developed. However, although several P2X receptor structures from different subtypes have been reported, the limited structural information of P2X receptors in complex with competitive antagonists hampers the understanding of orthosteric inhibition, hindering the further design and optimization of those antagonists for drug discovery. We determined the cryogenic electron microscopy (cryo-EM) structures of the mammalian P2X7 receptor in complex with two classical competitive antagonists of pyridoxal-5'-phosphate derivatives, pyridoxal-5'-phosphate-6-(2'-naphthylazo-6'-nitro-4',8'-disulfonate) (PPNDS) and pyridoxal phosphate-6-azophenyl-2',5'-disulfonic acid (PPADS), and performed structure-based mutational analysis by patch-clamp recording as well as molecular dynamics (MD) simulations. Our structures revealed the orthosteric site for PPADS/PPNDS, and structural comparison with the previously reported apo- and ATP-bound structures showed how PPADS/PPNDS binding inhibits the conformational changes associated with channel activation. In addition, structure-based mutational analysis identified key residues involved in the PPNDS sensitivity of P2X1 and P2X3, which are known to have higher affinity for PPADS/PPNDS than other P2X subtypes., Competing Interests: DS, CY, FJ, YW, MI, YY, CG, MH No competing interests declared, (© 2023, Sheng, Yue et al.)

This study was conducted to investigate the effects of dietary energy levels on microorganisms and short-chain fatty acids (SCFAs) of rumen and the expression of tight junction proteins in Honghe Yellow cattle. A total of fifteen male Honghe Yellow cattle were randomly divided into three treatments (five replicates per treatment), consisting of formulated energy concentrations of 5.90 MJ/kg (high-energy diet, group H), 5.60 MJ/kg (medium-energy diet, group M) and 5.30 MJ/kg (low-energy diet, group L). The results showed that compared with group H, the expression of Claudin-1 in rumen epithelium of groups M and L was increased, but the expression of ZO-1 was decreased ( p  < 0.05). Moreover, compared with group H, group M down-regulated the expression of Occludin and Claudin-1 in the brain ( p  < 0.05). For rumen bacteria, the dominant phyla included Bacteroidetes and Firmicutes, the abundance of Actinobacteriota in groups M and L was significantly increased compared with group H ( p  < 0.05). At the genus level, the relative abundance of Corynebacterium , Eubacterium&#95;nodatum&#95;group and Neisseraceae in groups M and L was significantly decreased compared with group H ( p  < 0.05). For rumen fungi, the dominant phyla included Basidiomycota, Ascomycota and Neocariastigomycota, the relative abundance of Ascomycetes was significantly higher than that of groups M and L compared with group H ( p  < 0.05). At the genus level, the relative abundance of Neocelimastigaceae and Myceliophthora in groups M and L was significantly reduced compared with group H ( p  < 0.05). Furthermore, the expression of Claudin-1 in rumen epithelium was significantly positively correlated with Actinobacteriota , Corynebacterium and Neisseriaceae. The expression of ZO-1 in the spinal cord was significantly positively correlated with Myceliophthora . The expression of Occludin in brain was positively correlated with valerate content ( p  < 0.05). In summary, dietary energy levels affected the rumen microbiota of Honghe Yellow cattle. The expression of Claudin-1 in rumen epithelium and the total SCFAs concentration were increased with decreasing dietary energy levels, but the expression of Claudin-1 in brain and ZO-1 in the spinal cord were reduced with decreasing dietary energy levels. Meanwhile, the rumen microbiota and SCFAs were significantly correlated with the expression of TJP., 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 Yu, Zi, Fu, Fu, Li, Lv, Li, Wang and Leng.)

Background and Purpose: The P2X3 receptor, a trimeric ionotropic purinergic receptor, has emerged as a potential therapeutic target for refractory chronic cough (RCC). Nevertheless, gefapixant/AF-219, the only marketed P2X3 receptor antagonist, might lead taste disorders by modulating the human P2X2/3 (hP2X2/3) heterotrimer. Hence, in RCC drug development, compounds exhibiting strong affinity for the hP2X3 homotrimer and a weak affinity for the hP2X2/3 heterotrimer hold promise. An example of such a molecule is sivopixant/S-600918, a clinical Phase II RCC candidate with a reduced incidence of taste disturbance compared to gefapixant. Sivopixant and its analogue, (3-(4-([3-chloro-4-isopropoxyphenyl]amino)-3-(4-methylbenzyl)-2,6-dioxo-3,6-dihydro-1,3,5-triazin-1(2H)-yl)propanoic acid (DDTPA), exhibit both high affinity and high selectivity for hP2X3 homotrimers, compared with hP2X2/3 heterotrimers. The mechanism underlying the druggable site and its high selectivity remains unclear., Experimental Approach: To analyse mechanisms that distinguish this drug candidate from other inhibitors of the P2X3 receptors we used a combination of chimera construction, site covalent occupation, metadynamics, mutagenesis and whole-cell recording., Key Results: The high affinity and selectivity of sivopixant/DDTPA for hP2X3 receptors was determined by the tri-symmetric site located close to the upper vestibule. Substitution of only four amino acids inside the upper body domain of hP2X2 with those of hP2X3, enabled the hP2X2/3 heterotrimer to exhibit a similar level of apparent affinity for sivopixant/DDTPA as the hP2X3 homotrimer., Conclusion and Implications: From the receptor-ligand recognition perspective, we have elucidated the molecular basis of novel RCC clinical candidates' cough-suppressing properties and reduced side effects, offering a promising approach to the discovery of novel drugs that specifically target P2X3 receptors., (© 2023 British Pharmacological Society.)

Cutaneous drug reactions (CDRs) are common drug-induced allergic reactions that cause severe consequences in HIV/AIDS patients. The CCL17/CCR4 axis is involved in the immune mechanism of allergic diseases, but its role in the CDRs has not been determined. Here, we aimed to determine the role of the CCL17/CCR4 axis and the underlying mechanism involved in CDRs. In this study, the serum cytokine levels in patients with CDR and healthy controls were measured. The CCL17-triggered allergic profile was screened via a PCR array. Apoptosis of keratinocytes cocultured with CCL17-stimulated Th2 cells was analyzed by flow cytometry. An NVP-induced rat CDR model was established, and dynamic inflammatory factor levels and Th2 cells in the peripheral blood of the rats were measured. Rat skin lesions and signaling pathways in Th2 cells were also analyzed. We showed that the serum CCL17 level was significantly upregulated in CDR patients (P = 0.0077), and the Th2 cell subgroup was also significantly elevated in the CDR rats. The CCL17/CCR4 axis induces Th2 cells to release IL-4 and IL-13 via the ERK/STAT3 pathway. The CCR4 antagonist compound 47 can alleviate rash symptoms resulting from NVP-induced drug eruption, Th2 cell subgroup, IL-4, and IL-13 and inhibit keratinocyte apoptosis. Taken together, these findings indicate that the CCL17/CCR4 axis mediates CDR via the ERK/STAT3 pathway in Th2 cells and type 2 cytokine-induced keratinocyte apoptosis., 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.)

Genetically engineered silkworms have been widely used to obtain silk with modified characteristics especially by introducing spider silk genes. However, these attempts are still challenging due to limitations in transformation strategies and difficulties in integration of the large DNA fragments. Here, we describe three different transformation strategies in genetically engineered silkworms, including transcription-activator-like effector nuclease (TALEN)-mediated fibroin light chain (FibL) fusion (BmFibL-F), TALEN-mediated FibH replacement (BmFibH-R), and transposon-mediated genetic transformation with the silk gland-specific fibroin heavy chain (FibH) promoter (BmFibH-T). As the result, the yields of exogenous silk proteins, a 160 kDa major ampullate spidroin 2 (MaSp2) from the orb-weaving spider Nephila clavipes and a 226 kDa fibroin heavy chain protein (EvFibH) from the bagworm Eumeta variegate , reach 51.02 and 64.13% in BmFibH-R transformed cocoon shells, respectively. Moreover, the presence of MaSp2 or EvFibH significantly enhances the toughness of genetically engineered silk fibers by ∼86% in BmFibH-T and ∼80% in BmFibH-R silkworms, respectively. Structural analysis reveals a substantial ∼40% increase in fiber crystallinity, primarily attributed to the presence of unique polyalanines in the repetitive sequences of MaSp2 or EvFibH. In addition, RNA-seq analysis reveals that BmFibH-R system only causes minor impact on the expression of endogenous genes. Our study thus provides insights into developing custom-designed silk production using the genetically engineered silkworm as the bioreactor., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Purpose: Down syndrome (DS) is a developmental disability associated with difficulties in deglutition. The adult Ts65Dn mouse model of DS has been previously shown to have differences in measures of swallowing compared with euploid controls. However, the putative mechanisms of these differences in swallowing function are unclear. This study tested the hypothesis that the Ts65Dn genotype is associated with atypical measures of tongue muscle contractile properties, coinciding with atypical swallow function., Methods: Adult (5-month-old) Ts65Dn ( n  = 15 female, 14 male) and euploid sibling controls ( n  = 16 female, 14 male) were evaluated through videofluoroscopy swallow studies (VFSS) to quantify measures of swallowing performance including swallow rate and inter-swallow interval (ISI). After VFSS, retrusive tongue muscle contractile properties, including measures of muscle fatigue, were determined using bilateral hypoglossal nerve stimulation., Results: The Ts65Dn group had significantly slower swallow rates, significantly greater ISI times, significantly slower rates of tongue force development, and significantly greater levels of tongue muscle fatigue, with lower retrusive tongue forces than controls in fatigue conditions., Conclusion: Tongue muscle contractile properties are altered in adult Ts65Dn and coincide with altered swallow function., 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 Glass, Russell, Fisher, Ostadi, Aori, Yu and Connor.)

Reproduction, a fundamental feature of all known life, closely correlates with energy homeostasis. The control of synthesizing and mobilizing lipids are dynamic and well-organized processes to distribute lipid resources across tissues or generations. However, how lipid homeostasis is precisely coordinated during insect reproductive development is poorly understood. Here we describe the relations between energy metabolism and reproduction in the silkworm, Bombyx mori, a lepidopteran model insect, by using CRISPR/Cas9-mediated mutation analysis and comprehensively functional investigation on two major lipid lipases of Brummer (BmBmm) and hormone-sensitive lipase (BmHsl), and the sterol regulatory element binding protein (BmSrebp). BmBmm is a crucial regulator of lipolysis to maintain female fecundity by regulating the triglyceride (TG) storage among the midgut, the fat body, and the ovary. Lipidomics analysis reveals that defective lipolysis of females influences the composition of TG and other membrane lipids in the BmBmm mutant embryos. In contrast, BmHsl mediates embryonic development by controlling sterol metabolism rather than TG metabolism. Transcriptome analysis unveils that BmBmm deficiency significantly improves the expression of lipid synthesis-related genes including BmSrebp in the fat body. Subsequently, we identify BmSrebp as a key regulator of lipid accumulation in oocytes, which promotes oogenesis and cooperates with BmBmm to support the metabolic requirements of oocyte production. In summary, lipid homeostasis plays a vital role in supporting female reproductive success in silkworms., (© 2024. The Author(s).)

Background: Cerebral ischemia has the characteristics of high incidence, mortality, and disability, which seriously damages people's health. Cerebral ischemia-reperfusion injury is the key pathological injury of this disease. However, there is a lack of drugs that can reduce cerebral ischemia-reperfusion injury in clinical practice. At present, a few studies have provided some evidence that nuciferine can reduce cerebral ischemia-reperfusion injury, but its specific mechanism of action is still unclear, and further research is still needed., Objective: In this study, PC12 cells and SD rats were used to construct OGD/R and MCAO/R models, respectively. Combined with bioinformatics methods and experimental verification methods, the purpose of this study was to conduct a systematic and comprehensive study on the effect and mechanism of nuciferine on reducing inflammation induced by cerebral ischemia-reperfusion injury., Results: Nuciferine can improve the cell viability of PC12 cells induced by OGD/R, reduce apoptosis, and reduce the expression of inflammation-related proteins; it can also improve the cognitive and motor dysfunction of MCAO/R-induced rats by behavioral tests, reduce the area of cerebral infarction, reduce the release of inflammatory factors TNF-α and IL-6 in serum and the expression of inflammation-related proteins in brain tissue., Conclusion: Nuciferine can reduce the inflammatory level of cerebral ischemia-reperfusion injury in vivo and in vitro models by acting on the PI3K/Akt/NF-κB signaling pathway, and has the potential to be developed as a drug for the treatment of cerebral ischemia-reperfusion injury., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier GmbH.)

Common ancestor of vertebrates had four cone opsin subfamilies to obtain color vision: ultraviolet-sensitive (SWS1), blue-sensitive (SWS2), middle wavelength sensitive (RH2) and long wavelength sensitive (LWS). Nevertheless, eutherian mammals had lost the SWS2 and RH2 opsins during their nocturnal lifestyle. Many studies had demonstrated the role of SWS1 and LWS cones in feeding, mate choice and skin pigment cell formation. However, the role of SWS2 and RH2 cones remain elusive. In the present study, we used an ideal model visual system, zebrafish, which still have the four cone opsins, to generate a SWS2 knockout zebrafish line. Through various behavioral test, we found that sws2 -/- zebrafish larvae exhibited increased food intake compared with WT. Additionally, there were significantly increased the gene expression of phototransduction pathways in sws2 -/- zebrafish larvae. Compared to WT, mutant zebrafish showed weaker phototaxis of red light and changed sensitivity of yellow, red and blue lights. But both mutant and WT zebrafish preferred the red light than other wavelengths of light. Taken together, we proposed that SWS2 cone is not necessary for feeding and phototaxis in zebrafish., 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. Published by Elsevier B.V.)

Recent epidemiological studies suggest that individuals with Down syndrome are more susceptible to SARS-CoV-2 infection and have higher rates of hospitalization and mortality than the general population. However, the main drivers behind these disparate health outcomes remain unknown. Herein, we performed experimental infections with SARS-CoV-2 in a well-established mouse model of Down syndrome. We observed similar SARS-CoV-2 replication kinetics and dissemination in the primary and secondary organs between mice with and without Down syndrome, suggesting that both groups have similar susceptibilities to SARS-CoV-2 infection. However, Down syndrome mice exhibited more severe disease as defined by clinical features including symptoms, weight loss, pulmonary function, and survival of mice. We found that increased disease severity in Down syndrome mice could not be attributed solely to increased infectivity or a more dramatic pro-inflammatory response to infection. Rather, results from RNA sequencing suggested that differences in the expression of genes from other physiological pathways, such as deficient oxidative phosphorylation, cardiopulmonary dysfunction, and deficient mucociliary clearance in the lungs may also contribute to heightened disease severity and mortality in Down syndrome mice following SARS-CoV-2 infection.

Field Oriented Control (FOC) effectively realizes independent control of flux linkage and torque, and is widely used in application of Permanent Magnet Synchronous Motor (PMSM). However, it is necessary to detect the phase current information of the motor to realize the current closed-loop control. The phase current detection method based on a sampling resistor will cause a measurement error due to the influence of parasitic parameters of the sampling resistor, which will lead to the decrease in PMSM control performance. This paper reveals the formation mechanism of the current sampling error caused by parasitic inductance and capacitance of the sampling resistor, and further confirms that the above error will lead to the fluctuation of the electromagnetic torque output by simulation. Moreover, we propose an approach for online observation and compensation of the current sampling error based on PI-type observer to suppresses the torque pulsation of PMSM. The phase current sampling error is estimated by the proportional and integral (PI) observer, and the deviation value of current sampling is obtained by low-pass filter (LPF). The above deviation value is further injected into the phase current close-loop for error compensation. The PI observer continues to work to keep the current sampling error close to zero. The simulation platform of Matlab/Simulink (Version: R2021b) is established to verify the effectiveness of online error observation and compensation. Further experiments also prove that the proposed method can effectively improve the torque fluctuation of the PMSM and enhance its control accuracy performance of rotation speed.

It is commonly believed that topologically nontrivial one-dimensional systems support edge states rather than bulk states at zero energy. In this work, we find an unanticipated case of topological Anderson insulator (TAI) phase where two bulk modes are degenerate at zero energy, in addition to degenerate edge modes. We term this "ungapped TAI" to distinguish it from the previously known gapped TAIs. Our experimental realization of both gapped and ungapped TAIs relies on coupled photonic resonators, in which the disorder in coupling is judiciously engineered by adjusting the spacing between the resonators. By measuring the local density of states both in the bulk and at the edges, we demonstrate the existence of these two types of TAIs, together forming a TAI plateau in the phase diagram. Our experimental findings are well supported by theoretical analysis. In the ungapped TAI phase, we observe stable coexistence of topological edge states and localized bulk states at zero energy, highlighting the distinction between TAIs and traditional topological insulators.

Photoaging refers to the accumulation of skin damage which includes wrinkle formation, loss of elasticity, and epidermal thickening due to repeated ultraviolet (UV) irradiation. The present study investigated the protective effects of Elaeagnus umbellata fruit extract (Elaea) on UV-mediated photoaged skin of SKH1 hairless mice and compared the effects of Elaea with ascorbic acid. Although there was no difference in body weight between groups during experimental period, oral administration of 50-200 mg/kg Elaea once daily for 15 weeks significantly prevented an increase in skin weight, epithelial thickening of epidermis, and apoptosis caused by UV irradiation. Skin replica and histopathological analyses revealed that Elaea dose-dependently decreased wrinkle and microfold formation. In addition, Elaea administration restored UV-mediated reduction in type I collagen and hyaluronan through the inhibition of matrix metalloproteinases and p38 mitogen-activated protein kinase expression. Moreover, Elaea suppressed UV-dependent increases in superoxide anion production, fatty acid oxidation, and protein nitration by up-regulating antioxidant system. Furthermore, Elaea alleviated infiltration of inflammatory cells in UV-irradiated skin. The preventive effects of 100 mg/kg Elaea administration against UV-induced photoaging were similar to those by 100 mg/kg ascorbic acid. Collectively, the present study suggests that the E. umbellata fruit is a promising edible candidate to prevent skin photoaging.