[Mechanism of Huangqin Qingre Chubi Capsules regulating p53/p21 signaling pathway to delay chondrocyte senescence in osteoarthritic rats].

This study aims to investigate the mechanism of Huangqin Qingre Chubi Capsules(HQC) in delaying chondrocyte senescence of osteoarthritic(OA) rats by regulating the p53/p21 signaling pathway. Rheumatic fever paralysis models of OA rats were induced based on monosodiun iodoacetate(MIA) combined with external rheumatic fever environmental stimuli and divided into normal(Con) group, OA model(MIA) group, OA model+rheumatic fever stimulation model(MIA-M) group, MIA-M+HQC low-dose(MIA-M+HQC-L) group, medium-dose(MIA-M+HQC-M) group, and high-dose(MIA-M+HQC-H) group, and MIA-M+glucosamine(MIA-M+GS) group. The models were successfully prepared and administered by gavage for 30 d. The pathological changes of cartilage were observed by hematoxylin-eosin(HE) and Senna O solid green(SO) staining. The expression of interleukin(IL)-1ß and IL-6 was detected by enzyme-linked immunosorbent assay(ELISA). Flow cytometry(FCM) was used to detect apoptosis and cell cycle. The mRNA expression of MMP13, ADAMTS-5, COLⅡ, and TGF-ß was detected by RT-qPCR. The protein expression of p53/p21, p16, Bax, and Bcl-2 was detected by Western blot. The articular cartilage surface of rats in the Con group was smooth, and the tide line was smooth. The cartilage layer of MIA and MIA-M groups was obviously damaged, and the cartilage matrix was reduced. The above conditions were more severe in the MIA-M group. The cartilage surface of the HQC high-dose group and MIA-M+GS group was basically intact with clear delamination. Compared with the MIA-M+HQC-H group, Mankin's score was higher in the HQC low-dose and medium-dose groups, and the change was not obvious in the MIA-M+GS group. Compared with the Con group, the proportion of chondrocytes G_1 was elevated in the MIA and MIA-M groups, and the proportion of the S phase and G_2 phase was significantly decreased. In addition, the apoptosis rate was increased. Compared with MIA-M, HQC groups inhibited apoptosis and promoted cell proliferation in a concentration-dependent manner. Compared with the MIA-M+HQC-H group, the effect was more significant in the HQC high-dose group than in the HQC medium-low dose, while it was not significant in the MIA-M+GS group. Compared with the Con group, IL-1ß and IL-6 were elevated in the MIA and MIA-M groups, and mRNA levels of MMP13 and ADAMTS-5 were elevated. p53, p21, p16, and Bax protein were elevated, and mRNA levels of COLⅡ and TGF-ß were decreased. Compared with the MIA-M group, IL-1ß and IL-6 decreased after drug interventions of HQC and GS, and mRNA levels of MMP13 and ADAMTS-5, as well as protein levels of p53, p21, Bax, and p16 decreased. In addition, Bcl-2 increased. The improvement of these indexes was significantly better in the MIA-M+HQC-H group than in the HQC low-dose and medium-dose groups, and the difference with the MIA-M+GS group was not significant. HQC delayed MIA-induced chondrocyte senescence in OA rats, inhibited inflammatory response and extracellular matrix(ECM) degradation, and its mechanism may be related to the inhibition of the p53/p21 pathway.

Validation of Jianpi Qingre Tongluo Recipe in Reducing Inflammation and Dyslipidemia in Osteoarthritis via Lnc RNA HOTAIR/APN/PI3K/AKT.

Objective: Jianpi Qingre Tongluo Recipe (JQP) has been widely used in clinical practice, and its anti-Osteoarthritis (OA) effectiveness and specific mechanism have been concerned. This study aims to explore the clinical effect of JQP in reducing inflammation and dyslipidemia in OA and the molecular mechanism. Methods: The clinical efficacy of JQP in OA treatment was assessed through data mining. Through the network pharmacology technology, the interactive network of "active component-target-disease" was developed, the interaction relationship of the related proteins was analyzed, and enrichment analysis of gene pathway biological process was conducted. Molecular docking was carried out with PyMOL and AutodockTools-1.5.7. Finally, cell experiments were used to verify JQP's delay of immune inflammation in OA. Results: We found that JQP could ameliorate the immune inflammatory and lipid metabolism indicators; reduce VAS and SAS score in OA. A total of 98 genes overlapped between target genes of JQP and OA. TNF, IL-6, IL-1ß, and AKT1 shared the highest centrality among all target genes. KEGG analysis unveiled that 98 intersection genes were predominantly enriched in PI3K/AKT pathway in the anti-OA system. In vitro, after peripheral blood mononuclear cell (PBMC) stimulation, inflammatory cytokines imbalances and the expressions of adiponectin (APN) were decreased in osteoarthritis-chondrocytes (OA-CH). Furthermore, JQP-containing serum protected OA-CHs through down-regulating HOTAIR levels, thereby up-regulating APN and depressing PI3K/AKT pathway. Conclusion: This study suggests that JQP might reduce inflammation and improve lipid metabolism of OA by regulating HOTAIR/APN/PI3K/AKT. Our results bring a new solution for OA.

Molecular Mechanisms and Therapeutic Targeting of Ferroptosis in Doxorubicin-Induced Cardiotoxicity.

Ferroptosis, an iron-dependent form of regulated cell death, has received increasing attention for its pathophysiologic contribution to the onset and development of doxorubicin-induced cardiotoxicity. Moreover, modulation of ferroptosis with specific inhibitors may provide new therapeutic opportunities for doxorubicin-induced cardiotoxicity. Here, we will review the molecular mechanisms and therapeutic promise of targeting ferroptosis in doxorubicin-induced cardiotoxicity.

PD-L2 mediates tobacco smoking-induced recruitment of regulatory T cells via the RGMB/NFκB/CCL20 cascade.

Programmed cell death ligand 2 (PD-L2), a ligand for the receptor programmed cell death 1 (PD-1), has an identity of 34% with its twin ligand PD-L1 and exhibits higher binding affinity with PD-1 than PD-L1. However, the role of PD-L2 in non-small cell lung cancer (NSCLC) progression, especially tobacco-induced cancer progression, has not been fully understood. Here, we found that PD-L2 promoted tumor growth in murine models with recruitment of regulatory T cells (Tregs). In patients with NSCLC, PD-L2 expression level in tumor samples was higher than in counterpart normal controls and was positively associated with patients' response to anti-PD-1 treatment. Mechanismly, PD-L2 bound its receptor Repulsive guidance molecule B (RGMB) on cancer cells and activated extracellular signal-regulated kinase (Erk) and nuclear factor κB (NFκB), leading to increased production of chemokine CCL20, which recruited Tregs and contributed to NSCLC progression. Consistently, knockdown of RGMB or NFκB p65 inhibited PD-L2-induced CCL20 production, and silencing of PD-L2 repressed Treg recruitment by NSCLC cells. Furthermore, cigarette smoke and carcinogen benzo(a)pyrene (BaP) upregulated PD-L2 in lung epithelial cells via aryl hydrocarbon receptor (AhR)-mediated transcription activation, whose deficiency markedly suppressed BaP-induced PD-L2 upregulation. These results suggest that PD-L2 mediates tobacco-induced recruitment of Tregs via the RGMB/NFκB/CCL20 cascade, and targeting this pathway might have therapeutic potentials in NSCLC.

Centipeda minima and 6-O-angeloylplenolin enhance the efficacy of immune checkpoint inhibitors in non-small cell lung cancer.

BACKGROUND: Chemotherapeutic agents including cisplatin, gemcitabine, and pemetrexed, significantly enhance the efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) by increasing PD-L1 expression and potentiating T cell cytotoxicity. However, the low response rate and adverse effects limit the application of chemotherapy/ICI combinations in patients. METHODS: We screened for medicinal herbs that could perturb PD-L1 expression and enhance T cell cytotoxicity in the presence of anti-PD-L1 antibody, and investigated the underlying mechanisms. RESULTS: We found that the aqueous extracts of Centipeda minima (CM) significantly enhanced the cancer cell-killing activity and granzyme B expression level of CD8+ T cells, in the presence of anti-PD-L1 antibody. Both CM and its active component 6-O-angeloylplenolin (6-OAP) upregulated PD-L1 expression by suppressing GSK-3ß-ß-TRCP-mediated ubiquitination and degradation. CM and 6-OAP significantly enhanced ICI-induced reduction of tumor burden and prolongation of overall survival of mice bearing NSCLC cells, accompanied by upregulation of PD-L1 and increase of CD8+ T cell infiltration. CM also exhibited anti-NSCLC activity in cells and in a patient-derived xenograft mouse model. CONCLUSIONS: These data demonstrated that the induced expression of PD-L1 and enhancement of CD8+ T cell cytotoxicity underlay the beneficial effects of 6-OAP-rich CM in NSCLCs, providing a clinically available and safe medicinal herb for combined use with ICIs to treat this deadly disease.

Highly Reversible Tin Film Anode Guided via Interfacial Coordination Effect for High Energy Aqueous Acidic Batteries.

Sn metal is a preferable choice as anode material for aqueous acidic batteries due to its acid-tolerance, non-toxicity, and ease of recycling. However, the large size and irregular deposition morphology of polyhedral Sn particles are bad for constructing stable and high-capacity Sn metal anode because of severe hydrogen evolution and metal shedding. To tackle this critical issue, 4-tert-octylphenol pentaethoxylate (POPE) is used as an electrolyte additive to generate a thin-film Sn anode with reversible stripping/plating behavior. POPE can not only induce homogeneous surface chemistry by adsorbing on the Sn surface via coordination bonds but also inhibit hydrogen evolution by modulating the solvation shell of Sn2+. The Sn film anode delivers improved electrochemical stability over 480 h with satisfactory rate performance and low polarization. Moreover, the as-assembled PbO2//Sn battery can also provide outstanding durability at 10 mAh cm-2. This work offers new inspiration for developing a reversible Sn metal film anode.

Ultrasensitive monitoring of PCB77 in environmental samples using a visible-driven photoelectrochemical sensing platform coupling with exonuclease I assisted in target recycling.

Due to the urgent need for detecting trace amounts of 3,3',4,4'-tetrachlorobiphenyl (PCB77) in the environment, we have developed an efficient and visible-driven photoelectrochemical (PEC) sensing platform based on carbon quantum dots (CQDs) modified titanium dioxide nanorods (TiO2 NRs), coupling with exonuclease I (Exo I) assisted in target recycling for significant signal amplification. CQDs/TiO2 NRs with high visible-light absorption ability and electron-hole separation efficiency is used as photoactive substrate for anchoring anti-PCB77 aptamer and its complementary DNA (cDNA). With the addition of PCB77, the specific interaction between PCB77 and its aptamer forces aptamer to separate from the electrode surface, resulting in an increase in photocurrent density. Adding Exo I in the test system, a self-catalytic target cycle was motivated, which significantly increased the PEC signal by more than twice, achieving signal amplification. The relationship between the photocurrent density changes and the concentrations of PCB77 are utilized to achieve quantitative detection of PCB77. The designed PEC sensing platform has good analytical performance with a detection limit as low as 0.33 pg L-1, high selectivity and stability. Moreover, the PEC sensor is successfully used to evaluate the content of PBC77 in the environment samples. The established sensing platform provides a simple and efficient method for detecting trace amounts of PCB77 in the environment.

Oncogenic functions and therapeutic potentials of targeted inhibition of SMARCAL1 in small cell lung cancer.

Small cell lung cancer (SCLC) is a recalcitrant cancer characterized by high frequency loss-of-function mutations in tumor suppressors with a lack of targeted therapy due to absence of high frequency gain-of-function abnormalities in oncogenes. SMARCAL1 is a member of the ATP-dependent chromatin remodeling protein SNF2 family that plays critical roles in DNA damage repair and genome stability maintenance. Here, we showed that SMARCAL1 was overexpressed in SCLC patient samples and was inversely associated with overall survival of the patients. SMARCAL1 was required for SCLC cell proliferation and genome integrity. Mass spectrometry revealed that PAR6B was a downstream SMARCAL1 signal molecule which rescued inhibitory effects caused by silencing of SMARCAL1. By screening of 36 FDA-approved clinically available agents related to DNA damage repair, we found that an aza-anthracenedione, pixantrone, was a potent SMARCAL1 inhibitor which suppressed the expression of SMARCAL1 and PAR6B at protein level. Pixantrone caused DNA damage and exhibited inhibitory effects on SCLC cells in vitro and in a patient-derived xenograft mouse model. These results indicated that SMARCAL1 functions as an oncogene in SCLC, and pixantrone as a SMARCAL1 inhibitor bears therapeutic potentials in this deadly disease.

Wearable EMI Shielding Composite Films with Integrated Optimization of Electrical Safety, Biosafety and Thermal Safety.

Biomaterial-based flexible electromagnetic interference (EMI) shielding composite films are desirable in many applications of wearable electronic devices. However, much research focuses on improving the EMI shielding performance of materials, while optimizing the comprehensive safety of wearable EMI shielding materials has been neglected. Herein, wearable cellulose nanofiber@boron nitride nanosheet/silver nanowire/bacterial cellulose (CNF@BNNS/AgNW/BC) EMI shielding composite films with sandwich structure are fabricated via a simple sequential vacuum filtration method. For the first time, the electrical safety, biosafety, and thermal safety of EMI shielding materials are optimized integratedly. Since both sides of the sandwich structure contain CNF and BC electrical insulation layers, the CNF@BNNS/AgNW/BC composite films exhibit excellent electrical safety. Furthermore, benefiting from the AgNW conductive networks in the middle layer, the CNF@BNNS/AgNW/BC exhibit excellent EMI shielding effectiveness of 49.95 dB and ultra-fast response Joule heating performance. More importantly, the antibacterial property of AgNW ensures the biosafety of the composite films. Meanwhile, the AgNW and the CNF@BNNS layers synergistically enhance the thermal conductivity of the CNF@BNNS/AgNW/BC composite film, reaching a high value of 8.85 W m‒1 K‒1, which significantly enhances its thermal safety when used in miniaturized electronic device. This work offers new ideas for fabricating biomaterial-based EMI shielding composite films with high comprehensive safety.

[Identification of Osteoarthritis Inflamm-Aging Biomarkers by Integrating Bioinformatic Analysis and Machine Learning Strategies and the Clinical Validation]. / ç”Ÿç‰©ä¿¡æ¯å­¦å’Œæœºå™¨å­¦ä¹ ç­–ç•¥è¯†åˆ«éª¨å ³èŠ‚ç‚Žç‚Žæ€§è¡°è€ç”Ÿç‰©æ ‡å¿—ç‰©ä¸Žä¸´åºŠéªŒè¯.

Objective: To identify inflamm-aging related biomarkers in osteoarthritis (OA). Methods: Microarray gene profiles of young and aging OA patients were obtained from the Gene Expression Omnibus (GEO) database and aging-related genes (ARGs) were obtained from the Human Aging Genome Resource (HAGR) database. The differentially expressed genes of young OA and older OA patients were screened and then intersected with ARGs to obtain the aging-related genes of OA. Enrichment analysis was performed to reveal the potential mechanisms of aging-related markers in OA. Three machine learning methods were used to identify core senescence markers of OA and the receiver operating characteristic (ROC) curve was used to assess their diagnostic performance. Peripheral blood mononuclear cells were collected from clinical OA patients to verify the expression of senescence-associated secretory phenotype (SASP) factors and senescence markers. Results: A total of 45 senescence-related markers were obtained, which were mainly involved in the regulation of cellular senescence, the cell cycle, inflammatory response, etc. Through the screening with the three machine learning methods, 5 core senescence biomarkers, including FOXO3, MCL1, SIRT3, STAG1, and S100A13, were obtained. A total of 20 cases of normal controls and 40 cases of OA patients, including 20 cases in the young patient group and 20 in the elderly patient group, were enrolled. Compared with those of the young patient group, C-reactive protein (CRP), interleukin (IL)-6, and IL-1ß levels increased and IL-4 levels decreased in the elderly OA patient group (P<0.01); FOXO3, MCL1, and SIRT3 mRNA expression decreased and STAG1 and S100A13 mRNA expression increased (P<0.01). Pearson correlation analysis demonstrated that the selected markers were associated with some indicators, including erythrocyte sedimentation rate (ESR), IL-1ß, IL-4, CRP, and IL-6. The area under the ROC curve of the 5 core aging genes was always greater than 0.8 and the C-index of the calibration curve in the nomogram prediction model was 0.755, which suggested the good calibration ability of the model. Conclusion: FOXO3, MCL1, SIRT3, STAG1, and S100A13 may serve as novel diagnostic biomolecular markers and potential therapeutic targets for OA inflamm-aging.

Multi-interfaced Ni/C@RGO/PTFE composites for electromagnetic protection applications with high environmental stability and durability.

To efficiently address the growing electromagnetic pollution problem, it is urgently required to research high-performance electromagnetic materials that can effectively absorb or shield electromagnetic waves. In addition, the stability and durability of electromagnetic materials in complex practical environments is also an issue that needs to be noticed. Therefore, the starting point for our problem-solving is how to endow magnetic/dielectric multi-interfaced composite materials with excellent electromagnetic protection capability and environmental stability. In this study, magnetic/dielectric multi-interfaced Ni/carbon@reduced graphene oxide/polytetrafluoroethylene (Ni/C@RGO/PTFE) composites were developed to utilize as excellent EWA (electromagnetic wave absorption) and EMI (electromagnetic interference) shielding materials. Due to their diverse heterogeneous interfaces, rich conductive networks, and multiple loss mechanisms, the Ni/C@RGO/PTFE composite exhibits an optimal reflection loss of -61.48 dB and an effective absorption bandwidth of 7.20 GHz, with a filler loading of 5 wt%. Furthermore, Ni/C@RGO/PTFE composite films have an optimal absorption effectiveness value of 9.50 dB and an absorption coefficient of 0.49. Moreover, Ni/C@RGO/PTFE can hold high EWA performance in various corrosive media and maintain more than 90% of EMI shielding effectiveness, which can be attributed to the carbon coating and PTFE matrix acting as dual protective barriers for the susceptible metal Ni, thus obviously improving the stability and durability of composites. Overall, this work presents an effective strategy for the growth of high-performance EWA and EMI shielding materials with outstanding environmental stability and durability, which have wide application prospects in the future.

CIP2A induces PKM2 tetramer formation and oxidative phosphorylation in non-small cell lung cancer.

Tumor cells are usually considered defective in mitochondrial respiration, but human non-small cell lung cancer (NSCLC) tumor tissues are shown to have enhanced glucose oxidation relative to adjacent benign lung. Here, we reported that oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) inhibited glycolysis and promoted oxidative metabolism in NSCLC cells. CIP2A bound to pyruvate kinase M2 (PKM2) and induced the formation of PKM2 tetramer, with serine 287 as a novel phosphorylation site essential for PKM2 dimer-tetramer switching. CIP2A redirected PKM2 to mitochondrion, leading to upregulation of Bcl2 via phosphorylating Bcl2 at threonine 69. Clinically, CIP2A level in tumor tissues was positively correlated with the level of phosphorylated PKM2 S287. CIP2A-targeting compounds synergized with glycolysis inhibitor in suppressing cell proliferation in vitro and in vivo. These results indicated that CIP2A facilitates oxidative phosphorylation by promoting tetrameric PKM2 formation, and targeting CIP2A and glycolysis exhibits therapeutic potentials in NSCLC.

Microwave-Absorbing Foams with Adjustable Absorption Frequency and Structural Coloration.

Microwave-absorbing materials with regulatable absorption frequency and optical camouflage hold great significance in intelligent electronic devices and advanced stealth technology. Herein, we present an innovative microwave-absorbing foam that can dynamically tune microwave absorption frequencies via a simple mechanical compression while in parallel enabling optical camouflage over broad spectral ranges by adjusting the structural colors. The vivid colors spanning different color categories generated from thin-film interference can be precisely regulated by adjusting the thickness of the conformal TiO2 coatings on Ni/melamine foam. Enhanced interfacial and defect-induced polarizations resulting from the introduction of TiO2 coating synergistically contribute to the dielectric attenuation performance. Consequently, such a foam exhibits exceptional microwave absorption capabilities, and the absorption frequency can be dynamically tuned from the S band to the Ku band by manipulating its compression ratio. Additionally, simulation calculations validate the adjustable electromagnetic wave loss behavior, offering valuable insights for the development of next-generation intelligent electromagnetic devices across diverse fields.

Flexible, Reliable, and Lightweight Multiwalled Carbon Nanotube/Polytetrafluoroethylene Membranes with Dual-Nanofibrous Structure for Outstanding EMI Shielding and Multifunctional Applications.

In this study, lightweight, flexible, and environmentally robust dual-nanofibrous membranes made of carbon nanotube (CNT) and polytetrafluoroethylene (PTFE) are fabricated using a novel shear-induced in situ fibrillation method for electromagnetic interference (EMI) shielding. The unique spiderweb-like network, constructed from fine CNTs and PTFE fibrils, integrates the inherent characteristics of these two materials to achieve high conductivity, superhydrophobicity, and extraordinary chemical resistance. The dual-nanofibrous membranes demonstrate a high EMI shielding effectiveness (SE) of 25.7-42.2 dB at a thickness range of 100-520 µm and the normalized surface-specific SE can reach up to 9931.1 dB·cm2·g-1, while maintaining reliability even under extremely harsh conditions. In addition, distinct electrothermal and photothermal conversion properties can be achieved easily. Under the stimulation of a modest electrical voltage (5 V) and light power density (400 mW·cm-2), the surface temperatures of the CNT/PTFE membranes can reach up to 135.1 and 147.8 °C, respectively. Moreover, the CNT/PTFE membranes exhibit swift, stable, and highly efficient thermal conversion capabilities, endowing them with self-heating and de-icing performance. These versatile, flexible, and breathable membranes, coupled with their efficient and facile fabrication process, showcase tremendous application potential in aerospace, the Internet of Things, and the fabrication of wearable electronic equipment for extreme environments.

Achieving stable Zn metal anode via a hydrophobic and Zn2+-conductive amorphous carbon interface.

High security and low cost enable aqueous zinc ion batteries (AZIBs) with huge application potential in large-scale energy storage. Nevertheless, the loathsome dendrite and side reactions of Zn anode are harmful to the cycling lifespan of AZIBs. Here, a new type of thin amorphous carbon (AC) interface layer (∼100 nm in thickness) is in-situ constructed on the Zn foil (Zn@AC) via a facile low-temperature chemical vapor deposition (LTCVD) method, which owns a hydrophobic peculiarity and a high Zn2+ transference rate. Moreover, this AC coating can homogenize the surface electric field and Zn2+ flux to realize the uniform deposition of Zn. Consequently, dendrite growth and side reactions are concurrently mitigated. Symmetrical cell achieves a dendrite-free Zn plating/stripping over 500 h with a low overpotential of 31 mV at 1 mA cm-2/1 mAh cm-2. Of note, the full cell with a MnO2/CNT cathode harvests a capacity retention of 70.0 % after 550 cycles at 1 A/g. In addition, the assembled flexible quasi-solid-state AZIBs display a stable electrochemical performance under deformation conditions and maintain a capacity of 76.5 mAh/g at 5 A/g after 300 cycles. This innovative amorphous carbon layer is expected to provide a new insight into stabilizing Zn anode.

Dry season temperature and rainy season precipitation significantly affect the spatio-temporal pattern of rubber plantation phenology in Yunnan province.

The ongoing global warming trajectory poses extensive challenges to plant ecosystems, with rubber plantations particularly vulnerable due to their influence on not only the longevity of the growth cycle and rubber yield, but also the complex interplay of carbon, water, and energy exchanges between the forest canopy and atmosphere. However, the response mechanism of phenology in rubber plantations to climate change remains unclear. This study concentrates on sub-optimal environment rubber plantations in Yunnan province, Southwest China. Utilizing the Google Earth Engine (GEE) cloud platform, multi-source remote sensing images were synthesized at 8-day intervals with a spatial resolution of 30-meters. The Normalized Difference Vegetation Index (NDVI) time series was reconstructed using the Savitzky-Golay (S-G) filter, coupled with the application of the seasonal amplitude method to extract three crucial phenological indicators, namely the start of the growing season (SOS), the end of the growing season (EOS), and the length of the growing season (LOS). Linear regression method, Pearson correlation coefficient, multiple stepwise regression analysis were used to extract of the phenology trend and find the relationship between SOS, EOS and climate factors. The findings demonstrated that 1) the phenology of rubber plantations has undergone dynamic changes over the past two decades. Specifically, the SOS advanced by 9.4 days per decade (R2 = 0.42, p< 0.01), whereas the EOS was delayed by 3.8 days per decade (R2 = 0.35, p< 0.01). Additionally, the LOS was extended by 13.2 days per decade (R2 = 0.55, p< 0.01); 2) rubber phenology demonstrated a notable sensitivity to temperature fluctuations during the dry season and precipitation patterns during the rainy season. The SOS advanced 2.0 days (r =-0.19, p< 0.01) and the EOS advanced 2.8 days (r =-0.35, p< 0.01) for every 1°C increase in the cool-dry season. Whereas a 100 mm increase in rainy season precipitation caused the SOS to be delayed by 2.0 days (r = 0.24, p< 0.01), a 100 mm increase in hot-dry season precipitation caused the EOS to be advanced by 7.0 days (r =-0.28, p< 0.01); 3) rubber phenology displayed a legacy effect of preseason climate variations. Changes in temperature during the fourth preseason month and precipitation during the fourth and eleventh preseason months are predominantly responsible for the variation in SOS. Meanwhile, temperature changes during the second, fourth, and ninth preseason months are primarily responsible for the variation in EOS. The study aims to enhance our understanding of how rubber plantations respond to climate change in sub-optimal environments and provide valuable insights for sustainable rubber production management in the face of changing environmental conditions.

Repurposing rabeprazole sodium as an anti-Clostridium perfringens drug by inhibiting perfringolysin O.

AIMS: Clostridium perfringens infections affect food safety, human health, and the development of the poultry feed industry. Anti-virulence is an alternative strategy to develop new drug. Perfringolysin O (PFO) is an exotoxin of C. perfringens that has been demonstrated to play critical roles in the pathogenesis of this organism, promising it an attractive target to explore drugs to combat C. perfringens infection. METHODS AND RESULTS: Based on an activity-based screening, we identified six PFO inhibitors from the Food and Drug Administration (FDA)-approved drug library, among which rabeprazole sodium (RS) showed an optimal inhibitory effect with an IC50 of 1.82 ± 0.746 µg ml-1. The GLY57, ASP58, SER190, SER193-194, ASN199, GLU204, ASN377, THR379, and ALA200 in PFO interacted with RS during binding based on an energy analysis and H-bond analysis. This interaction blocked the oligomer formation of PFO, thereby inhibiting its cytotoxicity. RS treatment significantly increased the survival rate and alleviated pathological damage in C. perfringens or PFO-treated Galleria mellonella. CONCLUSIONS: RS could potentially be used as a candidate drug for treating C. perfringens infection.

High frequency of alternative splicing variants of the oncogene Focal Adhesion Kinase in neuroendocrine tumors of the pancreas and breast.

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK6/7 in cells. These results suggested that FAK6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.

Ni-Carbon Microtube/Polytetrafluoroethylene as Flexible Electrothermal Microwave Absorbers.

Flexible microwave absorbers with Joule heating performance are urgently desired to meet the demands of extreme service environments. Herein, a type of flexible composite film is constructed by homogeneously dispersing a hierarchical Ni-carbon microtube (Ni/CMT) into a processable polytetrafluoroethylene (PTFE) matrix. The Ni/CMT are interconnected into a 3D conductive network, in which the huge interior cavity of the carbon microtube (CMT) improves impedance matching and provides additional hyper channels for electromagnetic (EM) waves dissipation, and the hierarchical magnetic Ni nanoparticles enhance the synergistic interactions between confined heterogeneous interfaces. Such an ingenious structure endows the composites with excellent electrothermal performance and improves their serviceability for application under extreme environments. Moreover, under a low fill loading of 3 wt.%, the Ni/CMT/PTFE (NCP) can achieve excellent low-frequency microwave absorption (MA) property with a minimum reflection loss of -59.12 dB at 5.92 GHz, which covers almost the entire C-band. Relying on their brilliant MA property, an EM sensor is designed and achieved by the resonance coupling of the patterned NCP. This work opens up a new way for the design of next-generation microwave absorbers that meet the requirements of EM packaging, proofing water and removing ice, fire safety, and health monitoring.

Carbon Nitride Grafting Modification of Poly(lactic acid) to Maximize UV Protection and Mechanical Properties for Packaging Applications.

Due to their biobased nature and biodegradability, poly(lactic acid) (PLA) rich blends are promising for processing in the packaging industry. However, pure PLA is brittle and UV transparent, which limits its application, so the exploration of nanocomposites with improved interfacial interactions and UV absorbing properties is worthwhile. We therefore developed and optimized synthesis routes for well-designed nanocomposites based on a PLA matrix and graphitic carbon nitride (g-C3N4; CN) nanofillers. To enhance the interfacial interaction with the PLA matrix, a silane-coupling agent (γ-methacryloxypropyl trimethoxysilane, KH570) is chemically grafted onto the CN surface after controlled oxidation with nitric acid and hydrogen peroxide. Interestingly, only 1 wt % of CNO-KH570, as synthesized under mild conditions, is needed to significantly improve the UV absorption, blocking even a large part of both UV-C, UV-B, and UV-A outperforming the UV absorption performance of PLA and, for instance, polyethylene terephthalate (PET). The low nanofiller loading of 1 wt % also results in a higher ductility with an increase in elongation at break (+73%), maintaining the tensile modulus. The results on a joint optimization of UV protection and mechanical properties are supported by a broad range of experimental characterizations, including FTIR, XRD, DSC, DSEM, FETEM, XPS, FTIR, TGA, and BET N2 adsorption-desorption analysis.