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How environmental factors affecting dissolved carbon remains unclear in lakes on the Qinghai-Tibetan Plateau (QTP), which limits the understanding of the lake carbon cycle. In this study, 60 lakes on the QTP in summer were investigated to clarify the variation in dissolved carbon, estimate dissolved carbon storage, and reveal how environmental factors affect the variation in dissolved carbon. The average dissolved organic carbon (DOC) and dissolved inorganic carbon (DIC) contents of 60 lakes on the QTP in summer were 12.78 mg/L and 103.66 mg/L, respectively. Salinity and total nitrogen were the important drivers of variations in DIC and DOC, respectively. Lake salinity and temperature were reduced only when precipitation was >50 mm, thus affecting the variations in lake dissolved carbon. Importantly, the elevation and area of the lake also significantly affected the variation in lake dissolved carbon. The total storage amounts of DOC and DIC in the 60 lakes on the QTP in summer were 58.94 Tg and 6.22 Tg, respectively. Lake area was the most direct factor influencing dissolved carbon storage in lakes on the QTP. Moreover, the TN and pH of the lake water also affected the DOC and DIC storage in the lakes, respectively. Interestingly, the lake pH at 9.1 was an important turning point that caused variations in lake DIC storage. Surprisingly, we found that rivers were able to transport 30 % of the DIC into QTP lakes and were the main source of DIC in the lakes in summer. The findings of this study clarify the sources of dissolved carbon and its drivers and improve our understanding of the carbon cycling processes in the lake system on the QTP., 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.)

Double wavelength emitting phosphors with hypersensitive thermal response are important for optical/thermal sensors and multiplexing optical data storage technology. However, it is a daunting challenge to develop multicolor electron-trapping materials with superheat sensitivity and anomalous quenching luminescence characteristics for information storage. Here, based on the selection of host lattice and the control of doping ion types, we have designed Mn 2+ - and/or Cr 3+ -activated persistent materials with excellent fluorescence properties. Among these phosphors, Mn,Cr co-activated biphasic mixture exhibits not only sensitive anomalous thermosensitive fluorescence properties but also multicolor and multimode fluorescence emission characteristics derived from Mn and Cr simultaneously. The corresponding multimode fluorescence mechanism is proposed based on afterglow energy transfer and deepening trap effect. Especially, based on the excellent fluorescence performances, these phosphors as information storage medium demonstrate multilevel information storage by a combination of the trap multiplexing and wavelength multiplexing technologies. The study here provides not only the ideas for designing and synthesizing new electronic materials but also a material foundation for the fourth generation of optical information storage and encryption., (© 2024 John Wiley & Sons Ltd.)

Osmotic pump systems require prolonged retention time in the stomach to provide enhanced bioavailability and regulated release, which is quite challenging. This study used a three-dimensional printing (3DP) technique combined with a gastro-retentive floating device (GRFD) to extend the retention of the osmotic pump in the stomach and enhance its bioavailability. The strap-on buoyant device was fabricated by stereolithography 3DP and incorporated a felodipine osmotic pump tablet used in clinical practice, which enabled it to float in the stomach or dissolution media without any floating lag time. The components of the device were affixed using a snap-fix mechanism. GRFD dissolution study revealed a notable in vitro floating capability, lasting over 24 h, with a release profile similarity factor f 2  = 65.28 compared to the naked tablet dissolution profile. The pharmacokinetics of felodipine osmotic pump in beagles showed a C max of 1.893 ng/mL, which increased to 4.511 ng/mL with GRFD. The delivery of an osmotic pump with GRFD enhanced the AUC 0-∞ of felodipine from 10.20 ng/mL·h to 26.54 ng/mL·h. In conclusion, the strap-on buoyant device has been successfully designed to enhance gastrointestinal tract retention of felodipine osmotic pumps and bioavailability in beagles., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

River CO 2 fluxes (FCO 2 ) play an important role in the carbon cycle of the Qinghai‒Tibet Plateau (QTP). However, the carbon budget of river water is ignored in the assessment of the carbon sources and sinks of ecosystems on the QTP, which makes the assessment of the carbon sinks of ecosystems uncertain on the QTP. Here, we selected rivers around alpine steppe, alpine meadow, forestland and bare land areas on the QTP to determine their FCO 2 values and control factors during thaw, rainy and freezing periods. The results revealed that river water around the alpine steppe absorbed CO 2 during the thaw and freezing periods, making it a carbon sink. The influencing factors of FCO 2 around different ecosystems significantly differed across the different periods. The pCO 2 was the most direct factor affecting the FCO 2 of river water. During the thaw period, the FCO 2 of rivers around the alpine steppe and bare land was affected mainly by dissolved organic carbon (DOC) and precipitation, respectively. The FCO 2 of rivers around the alpine meadow and forestland was affected by dissolved inorganic carbon (DIC). During the rainy period, the FCO 2 of the rivers around the alpine steppe and bare land was affected mainly by total nitrogen (TN) and salinity, respectively. The FCO 2 of rivers around the alpine meadow and forestland was affected by dissolved oxygen (DO) and DOC. During the freezing period, the FCO 2 of the rivers around the alpine steppe and bare land was affected mainly by TN and pCO 2 , respectively. The FCO 2 of rivers around the forestland and alpine meadow was affected by precipitation, runoff and DIC. The FCO 2 in rivers around vegetated areas were affected by rock weathering, aquatic ecosystem biology and hydrological processes to varying degrees at different times. However, rivers around bare ground were less affected by these processes. The FCO 2 values around the alpine steppe, alpine meadow, forestland and bare land were 1.40 g C/m 2 /d, 1.12 g C/m 2 /d, 2.29 g C/m 2 /d and 4.20 g C/m 2 /d, respectively. The river water around bare land released a large amount of CO 2 . Therefore, to reduce the CO 2 emissions of rivers on the QTP, it is urgent that we restore bare-land vegetation and promote the transfer of bare land to steppe, which is an effective way to increase the carbon sink of the ecosystems on the QTP., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Vitrification of oocyte has become an important component of assisted reproductive technology and has important implications for animal reproduction and the preservation of biodiversity. However, vitrification adversely affects mitochondrial function and oocyte developmental potential, mainly because of oxidative damage. Rutin is a highly effective antioxidant, but no information is available to the effect of rutin on the mitochondrial function and development in vitrified oocytes. Therefore, we studied the effects of rutin supplementation of vitrification solution on mitochondrial function and developmental competence of ovine germinal vesicle (GV) stage oocytes post vitrification. The results showed that supplementation of vitrification solution with 0.6 mM rutin significantly increased the cleavage rate (71.6 % vs. 59.3 %) and blastocyst rate (18.9 % vs. 6.8 %) compared to GV-stage oocytes in the vitrified group. Then, we analyzed the reactive oxygen species (ROS), glutathione (GSH), mitochondrial activity and membrane potential (ΔΨm), endoplasmic reticulum (ER) Ca 2+ , and annexin V (AV) of vitrified sheep GV-stage oocytes. Vitrified sheep oocytes exhibited increased levels of ROS and Ca 2+ , higher rate of AV-positive oocytes, and decreased mitochondrial activity, GSH and ΔΨm levels. However, rutin supplementation in vitrification solution decreased the levels of ROS, Ca 2+ and AV-positive oocytes rate, and increased the GSH and ΔΨm levels in vitrified oocytes. Results revealed that rutin restored mitochondrial function, regulated Ca 2+ homeostasis and decreased apoptosis potentially caused by mitophagy in oocytes. To understand the mechanism of rutin functions in vitrified GV-stage oocytes in sheep, we analyzed the transcriptome and found that rutin mediated oocytes development and mitochondrial function, mainly by affecting oxidative phosphorylation and the mitophagy pathways. In conclusion, supplementing with 0.6 mM rutin in vitrification solution significantly enhanced developmental potential through improving mitochondrial function and decreased apoptosis potentially caused by mitophagy after vitrification of ovine GV-stage oocytes., Competing Interests: Declaration of competing interest The authors declare that they have no interest conflict., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: This study examined the impacts of customer knowledge management and flow experience on customer value co-creation and the mediating role of flow experience in the context of fitness apps., Design/methodology/approach: Using the questionnaire star platform to edit the questionnaire and collect data(n = 450). A structural equation modeling test was conducted to examine the relationships between the variables., Findings: The findings reveal that in a fitness app service scenario, customer knowledge management has a significant positive impact on customer flow experience, customer flow experience has a significant positive impact on customer value co-creation, and customer flow experience plays a partial mediating role in the path from customer knowledge management to customer value co-creation., Practical Implications: The results could help fitness-app-related enterprises or service organizations understand the factors influencing and processes of customer participation in value co-creation and thus could help such enterprises and organizations formulate effective marketing strategies to realize customer value co-creation and ultimately to achieve their development goals., Originality/value: Using value co-creation theory and customer-dominant logic, this study analyzed the effects of customer knowledge management, flow experience, and customer value co-creation in the context of fitness apps and examined the mediating role of flow experience. The findings fill a gap in the theoretical research regarding customer value co-creation in the context of fitness apps and expand the scope of research on customer knowledge management and flow experience., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Long persistent luminescence (PersL) materials have revolutionized many fields of optoelectronics and photonics due to their applications in anticounterfeiting, information encryption, and in vivo bioimaging. Here, we reported a novel PersL crystal prepared by the heterovalent doping of Sb 3+ into perovskite tetragonal phase RbCdCl 3 , comparing with the pristine non-perovskite orthorhombic phase analogue without PersL property. Surprisingly, under the UV light irradiation, the title crystals concurrently exhibit green ultralong PersL (>2400 s), high photoluminescence quantum yield (49.1%), and antithermal quenching in the range from 148 to 328 K. It was revealed by experimental results and theoretical analyses that green ultralong PersL and antithermal quenching of perovskite-phase RbCdCl 3 /Sb 3+ crystals originate from the electron transition between the 5s 2 level of the dopant Sb 3+ and the electronic defect-induced trap states. Enlightened by the excellent optical properties, the tetragonal perovskite-phase RbCdCl 3 /Sb 3+ PersL materials show promising application prospects in anticounterfeiting and encryption of information.

Despite the promising advances in photodynamic therapy (PDT), it remains challenging to target and treat deep-seated solid tumors effectively. Herein, we developed an organoplatinum(II) complex ( Pt-TPE ) with self-assembly properties for sonodynamic therapy (SDT). Pt-TPE forms a nanofiber network structure through Pt-Pt and π-π stacking interactions. Notably, under ultrasound (US), Pt-TPE demonstrates unique self-assembly-induced singlet oxygen ( 1 O 2 ) generation due to a significantly enhanced singlet-triplet intersystem crossing (ISC). This generation of 1 O 2 occurs exclusively in the self-assembled state of Pt-TPE . Additionally, Pt-TPE exhibits sono-cytotoxicity against cancer cells by impairing mitochondrial membrane potential (MMP), inhibiting glucose uptake, and aerobic glycolysis. Furthermore, US-activated Pt-TPE significantly inhibits deep solid tumors in mice, achieving remarkable therapeutic efficacy even at penetration depths greater than 10 cm. This study highlights the potential of self-assembled metal complexes to enhance the efficacy of SDT for treating deep tumors.

Achieving full eradication of residual tumors post photothermal therapy (PTT) hinges on the immune system's activation and response. Nevertheless, the resultant local inflammation attracts a significant influx of aberrant immune cells and fibroblasts, such as tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), following tumor PTT. This phenomenon exacerbates immune evasion and the persistence of residual tumor cells, culminating in tumor recurrence and advancement. To tackle this challenge, a combined therapeutic approach utilizing multifunctional ICG-SB@Lip-ZA nanosystem has been introduced. Indocyanine green (ICG) as a photothermal-transducer ablated tumor cells, zoledronic acid (ZA) depletes TAMs recruited by the inflammatory tumor microenvironment (mostly M2-like phenotype), SB-505124 affects CAFs proliferation in the tumor microenvironment (TME) by inhibiting the transforming growth factor-β （TGF-β） pathway, thereby removing physical barriers to T cell infiltration. In a breast cancer model, these immunomodulatory nanoliposomes markedly decrease the population of M2-like TAMs in the TME, eliminate physical barriers hindering T cell infiltration, reshape the inflammatory immune-suppressive tumor microenvironment, eventually leading to a rate of tumor eradication of 94%. This multifunctional ICG-SB@Lip-ZA nanosystem (including photothermal conversion, TAM depletion, and TGF-β pathway blockade) offers a promising strategy for mitigating the deteriorating tumor microenvironment following PTT and presents a more efficient approach for clinical photothermal-immune combination therapy., (© 2024 Wiley‐VCH GmbH.)

Accumulation of coal gangue (CG) poses significant risks to both human health and ecological systems, underscoring the urgent need for sustainable methods to utilize this abundant waste material effectively. In this study, we successfully screened and isolated the Bacillus velezensis bacterial strain to enhance the solubilization of potassium (K) and phosphorus (P) nutrients from CG. The study employed XRD, FTIR, SEM, and HPLC techniques to investigate the underlying mechanisms of CG solubilization. Various parameters such as CG particle size, incubation time, initial inoculation ratio, concentration of CG, pH, and temperature were optimized to maximize solubilization efficiency. The Bacillus velezensis bacterium can dissolve minerals of CG by adhering to its surface and secreting various kinds of organic acids, particularly succinic acid. Pot experiments further demonstrated that Bacillus velezensis , in conjunction with CG, promotes alfalfa growth. These combined findings suggest that Bacillus velezensis and coal gangue hold promising potential as mineral soil conditioners, effectively enhancing plant growth. This approach presents a viable alternative for the environmentally responsible utilization of CG, addressing both ecological concerns and agricultural sustainability., Importance: Coal gangue piles not only occupy significant amounts of arable land but also cause serious environmental pollution. Therefore, finding sustainable methods for the clean utilization of CG is imperative. Although previous studies have shown that bacteria can promote the solubilization of available phosphorus and available potassium from CG, their impact on promoting plant growth remains understudied. To our knowledge, this study is the first to demonstrate the potential of Bacillus velezensis in enhancing the effectiveness of CG as a mineral fertilizer to support alfalfa growth. The evidence presented in this study provides an ecological strategy for the utilization of CG.

Aluminum (Al) toxicity in acid soils poses a significant threat to rice, which exhibits highly complex genetic mechanisms for both external detoxification and internal tolerance among cereal crops. Although several genes involved Al tolerance have been identified, the molecular mechanisms underlying Al tolerance in rice remain to be fully explored. Here, we functionally characterized the gibberellin-stimulated transcription gene OsGASR1, which encodes a small cysteine-rich peptide localized to the nucleus and cytoplasm and plays a significant role in Al tolerance in rice. The expression of OsGASR1 is rapidly up-regulated by Al in rice root tips but not in the shoots. Its expression is not regulated by the central regulator Aluminum Resistance Transcription Factor 1 (ART1), indicating that OsGASR1 functions as a novel gene in rice Al resistance independent of ART1. Knockout of OsGASR1 reduced root length but did not affect Al tolerance in rice, whereas overexpression of OsGASR1 enhanced Al tolerance without affecting Al distribution and accumulation and promoted the accumulation of reactive oxygen species (ROS) in the root tips. RNA-seq analysis revealed that overexpression of OsGASR1 upregulated the expression of genes associated with cell wall modification, oxidative stress, and Al tolerance. Collectively, these findings suggest that OsGASR1 is involved in Al tolerance in rice independently of ART1, and the up-regulation of this gene is necessary for rice Al tolerance., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The growing body of research on kidney disease in children has identified a broad spectrum of genetic etiologies., Methods: We conducted a prospective study to evaluate the efficacy of an optimized genetic test and subclinical changes in a real-world context before kidney transplantation. All cases involved recipients under the age of 18 who underwent whole exome sequencing (ES) between 2013 and 2022., Results: The study population included 244 children, with a median age of 13.1 years at transplantation. ES provided a molecular genetic diagnosis in 114 (46.7%) probands with monogenic variants in 15 known disease-causing genes. ES confirmed the suspected clinical diagnosis in 74/244 (30.3%) cases and revised the pre-exome clinical diagnoses in 40/244 (16.4%) cases. ES also established a specific underlying cause for kidney failure for 19 patients who had previously had an unknown etiology. Genetic diagnosis influenced clinical management in 88 recipients (36.1%), facilitated genetic counseling for 18 families (7.4%), and enabled comprehensive assessment of living donor candidates in 35 cases (14.3%)., Conclusions: Genetic diagnosis provides critical insights into the pathogenesis of kidney disease, optimizes clinical strategies concerning risk assessment of living donors, and enhances disease surveillance of recipients., (© 2024. The Author(s).)

Fusarium wilt is one of the major constraints on global watermelon production, and Fusarium oxysporum f. sp. niveum (Fon) is the causative agent of Fusarium wilt in watermelon and results in severe yield and quality losses worldwide. The enhancement of antifungal activity from antagonistic bacteria against Fon is highly practical for managing Fusarium wilt in watermelon. The aim of this study was to maximize the antifungal activity of Bacillus velezensis LZN01 by optimizing fermentation conditions and analysing its regulatory mechanism via transcriptome sequencing. The culture and fermentation conditions for strain LZN01 were optimized by single-factor and response surface experiments. The optimum culture conditions for this strain were as follows: the addition of D-fructose at 35 g/L and NH 4 Cl at 5 g/L in LB medium, pH 7, and incubation at 30°C for 72 h. The fungal inhibition rate for strain LZN01 reached 71.1%. The improvement of inhibition rate for strain LZN01 in optimization fermentation was supported by transcriptomic analysis; a total of 491 genes were upregulated, while 736 genes were downregulated. Transcriptome analysis revealed that some differentially expressed genes involved in carbon and nitrogen metabolism, oxidation-reduction, fatty acid and secondary metabolism; This optimization process could potentially lead to significant alterations in the production levels and types of antimicrobial compounds by the strain. Metabolomics and UPLC/Q-Exactive Orbitrap MS analysis revealed that the production yields of antimicrobial compounds, such as surfactin, fengycin, shikimic acid, and myriocin, increased or were detected in the cell-free supernatant (CFS) after the fermentation optimization process. Our results indicate that fermentation optimization enhances the antifungal activity of the LZN01 strain by influencing the expression of genes responsible for the synthesis of antimicrobial compounds., (© 2024 The Author(s). Microbial Biotechnology published by John Wiley & Sons Ltd.)

The metabolites of sweroside were first investigated in vivo with ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOF-MS) in combination with 2,4-dinitrophenylhydrazine derivatization. In addition, the mass detection sensitivity of the major metabolites, epinaucledal and naucledal, via UPLC-TOF-MS was significantly enhanced, and the epimer metabolites were distinctly discovered from plasma following gavage of sweroside in rats. The plasma concentration of epinaucledal and naucledal was quantified via UPLC-TOF-MS in negative mode using erythrocentaurin as the internal standard. The maximum mean plasma concentrations of naucledal and epinaucledal were 75.36 ± 20.10 and 43.52 ± 15.60 ng/ml within 2 h, respectively, following gavage of sweroside at 20 mg/kg. Moreover, the area under the concentration-time curve of naucledal was three times that of epinaucledal. The metabolic process of conversion of sweroside to epinaucledal and naucledal was deduced, and the pharmacological effects of epinaucledal and naucledal will clarify the clinical efficacy of sweroside., (© 2024 John Wiley & Sons Ltd.)

Purpose: Uterine serous carcinoma (USC) is generally associated with poor prognosis due to a high recurrence rate and frequent treatment resistance; hence, there is a need for improved therapeutic strategies. Molecular analysis of USC identified several molecular markers, useful to improve current treatments or identify new druggable targets. PPP2R1A, encoding the Aα subunit of the tumor suppressive Ser/Thr phosphatase PP2A, is mutated in up to 40% of USCs. Here, we investigated the effect of the p.R183W PPP2R1A hotspot variant on treatment response to the nucleoside analogue clofarabine., Methods and Results: USC cells stably expressing p.R183W Aα showed increased resistance to clofarabine treatment in vitro and, corroborated by decreased clofarabine-induced apoptosis, G1 phase arrest, DNA-damage (γH2AX) and activation of ATM and Chk1/2 kinases. Phenotypic rescue by pharmacologic PP2A inhibition or dicer-substrate siRNA (dsiRNA)-mediated B56δ subunit knockdown supported a gain-of-function mechanism of Aα p.R183W, promoting dephosphorylation and inactivation of deoxycytidine kinase (dCK), the cellular enzyme responsible for the conversion of clofarabine into its bioactive form. Therapeutic assessment of related nucleoside analogues (gemcitabine, cladribine) revealed similar effects, but in a cell line-dependent manner. Expression of two other PPP2R1A USC mutants (p.P179R or p.S256F) did not affect clofarabine response in our cell models, arguing for mutant-specific effects on treatment outcome as well., Conclusions: While our results call for PPP2R1A mutant and context-dependent effects upon clofarabine/nucleoside analogue monotherapy, combining clofarabine with a pharmacologic PP2A inhibitor proved synergistically in all tested conditions, highlighting a new generally applicable strategy to improve treatment outcome in USC., (© 2024. Springer Nature Switzerland AG.)

In this paper, for the sake of enhancing the security of wireless transmission, we proposed a novel system based on spatial and direction modulation (SDM) combined with generalized spatial modulation (GSM) which is aided by covert information mapping (CIM), termed as the CIM-GSDM system. In such a system, the legitimated user is equipped with distributed receivers so as to demodulate the conveyed signal by exploiting its indices while disturbing eavesdroppers for information security. More specifically, part of the information is modulated into the indices of the legitimated distributed receiver subsets with the aid of the mapped covert information and the interference matrix, while another part of the message is arranged by conventional amplitude-phase modulation. The proposed system can reap the benefits from both GSM and CIM to make eavesdropper suffer great mixture. Furthermore, the detection scheme and theoretical analysis of error performance are discussed as well. The simulation results exhibit that the bit error rate (BER) performance of legitimate user is much better than that of the eavesdropper while the proposed scheme improves the security compared to the original CIM-SDM system at the same spectral efficiency.

Objective: To evaluate the effectiveness of multimodal features based on gait analysis and eye tracking for elderly people screening with subjective cognitive decline in the community., Methods: In the study, 412 cognitively normal older adults aged over 65 years were included. Among them, 230 individuals were diagnosed with non-subjective cognitive decline and 182 with subjective cognitive decline. All participants underwent assessments using three screening tools: the traditional SCD9 scale, gait analysis, and eye tracking. The gait analysis involved three tasks: the single task, the counting backwards dual task, and the naming animals dual task. Eye tracking included six paradigms: smooth pursuit, median fixation, lateral fixation, overlap saccade, gap saccade, and anti-saccade tasks. Using the XGBoost machine learning algorithm, several models were developed based on gait analysis and eye tracking to classify subjective cognitive decline., Results: A total of 161 gait and eye-tracking features were measured. 22 parameters, including 9 gait and 13 eye-tracking features, showed significant differences between the two groups ( p  < 0.05). The top three eye-tracking paradigms were anti-saccade, gap saccade, and median fixation, with AUCs of 0.911, 0.904, and 0.891, respectively. The gait analysis features had an AUC of 0.862, indicating better discriminatory efficacy compared to the SCD9 scale, which had an AUC of 0.762. The model based on single and dual task gait, anti-saccade, gap saccade, and median fixation achieved the best efficacy in SCD screening (AUC = 0.969)., Conclusion: The gait analysis, eye-tracking multimodal assessment tool is an objective and accurate screening method that showed better detection of subjective cognitive decline. This finding provides another option for early identification of subjective cognitive decline in the community., 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 Hao, Zhang, An, Bao, Yang, Chen, Hou, Wang, Du, Zhao, Wang, Min and Li.)

Background: Connexin 43 (Cx43) plays a crucial role in mediating intracellular communication and facitating the interaction between exosomes and recipient cells. This study investigates whether the activation of cAMP/protein kinase A (PKA) can regulate exosomal Cx43 expression and contribute to the functional recovery following ischemia-reperfusion (I/R) injury., Methods: An intraluminal vascular occlusion was performed on Lewis rats to simulate I/R injury. Concurrently, a PKA activator (8-Bromo-cAMP, 5 mg kg -1 ) or PKA inhibitor (H 89 2HCl, 20 mg kg -1 ) was administered intravenously via the tail vein (n = 10). Exosomes were isolated from cerebrospinal fluid, and the expression of exosomal markers (CD63 and CD81) and Cx43 was analyzed using Western blot. The expression of CD63 and CD81 in astrocytes was measured to assess exosome uptake. Spatial learning and memory capability were evaluated using the Morris water maze test., Results: 8-Bromo-cAMP significantly increased exosome release in cerebrospinal fluid, accompanied by elevated Cx43 expression. Additionally, 8-Bromo-cAMP enhanced exosome uptake by astrocytes, alleviated blood-brain barrier damage and edema, and improved cognitive function., Conclsions: PKA activation enhances exosome production, promotes cognitive function recovery, and attenuates cerebral I/R injury by up-regulating exosomal Cx43 expression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The aim of the present study was to explore the relationship between the size of cesarean scar diverticulum (CSD) measured on preoperative magnetic resonance imaging (MRI) and adverse events during dilatation and curettage (D&C) procedure in patients with cesarean scar pregnancy (CSP)., Methods: The MRI of 197 CSP patients from October 2019 to August 2023 were retrospectively reviewed. The volume, area, and depth of CSD, residual myometrium thickness (RMT), and gestational sac diameter were recorded and tested for correlation with intraoperative estimated blood loss (EBL), and operation time and for any association with the intraoperative adverse events (intraoperative massive hemorrhage [39 cases] and D&C procedure failure [15 cases]). The Spearman test was used to characterize the correlation between the five MRI variables and both the EBL and operation time. The correlation between the five MRI variables and intraoperative adverse events was evaluated with student's t test and Mann-Whitney U test. Diagnostic power of the MRI variables was evaluated by the area under receiver operating characteristic curve (AUC)., Results: The volume, area, and depth of CSD and gestational sac diameter were positively correlated with both EBL and operation time, with the CSD volume having the highest correlation with them (r = 0.543 and 0.461, respectively). Conversely, the RMT displayed a negative correlation with the EBL and operation time. All five MRI variables were significantly associated with both intraoperative massive hemorrhage and D&C failure (all P < 0.001). The CSD volume demonstrated the highest AUC for diagnosing intraoperative massive hemorrhage and D&C failure at 0.893 (95% CI: 0.82-0.92) and 0.901 (95% CI: 0.85-0.94), respectively. The optimal cutoff values for CSD volume in predicting massive hemorrhage and D&C failure were determined to be 5.41 and 8.92 cm 3 , respectively, with corresponding sensitivities/specificities of 92.31/74.68 and 93.33/82.42, respectively., Conclusion: Quantifying the size of CSD based on preoperative MRI could aid in evaluating risk during D&C in CSP patients, with CSD volume possessing higher diagnostic efficacy than the other four MRI indicators., (© 2024 International Federation of Gynecology and Obstetrics.)

The utilization of photothermal agents (PTAs) in photothermal therapy (PTT) is faced with challenges such as immune clearance and inadequate concentration, which consequently result in residual tumors and an increased risk of recurrence and metastasis. Conversely, excessive treatment can lead to heightened inflammation and inevitable harm to adjacent healthy tissues. To address these issues, we developed a nanosystem (M@PB) consisting of Prussian blue coated with tumor cell membrane for precise photothermal therapy (PTT) and subsequent reduction of inflammation. This system not only evades immune attack due to the homologous biological characteristics of the encapsulating cell membrane but also exhibits active targeting capabilities towards homologous tumors. Furthermore, it effectively reduces excessive phototoxicity by leveraging the distinctive photothermal and anti-inflammatory characteristics of PB nanoparticles. The resulting M@PB nanosystem demonstrates effective photothermal ablation under 808 nm laser irradiation while mitigating the inflammatory response through inhibiting of local production of inflammatory mediators. Our study provides valuable insights into achieving targeted PTT with high efficiency while minimizing post-treatment inflammatory responses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Amplifying oxidative stress to disrupt intracellular redox homeostasis can accelerate tumor cell death. In this work, an oxidative stress amplifier (PP@T) is prepared for enhanced tumor oxidation therapy to reduce tumor growth and metastases. The nano-amplifier has been successfully constructed by embedding MTH1 inhibitor (TH588) in the PDA-coated porphyrin metal-organic framework PCN-224. The controllable-released TH588 is demonstrated from pores can hinder MTH1-mediated damage-repairing process by preventing the hydrolysis of 8-oxo-dG, thereby amplifying oxidative stress and exacerbating the oxidative DNA damage induced by the sonodynamic therapy of PP@T under ultrasound irradiation. Furthermore, PP@T can effectively induce immunogenic cell death to trigger systemic anti-tumor immune response. When administered in combination with immune checkpoint blockade, PP@T not only impedes the progression of the primary tumor but also achieves obvious antimetastasis in breast cancer murine models, including orthotopic and artificial whole-body metastasis models. Furthermore, the nanoplatform also provides photoacoustic imaging for in vivo treatment guidance. In conclusion, by amplifying oxidative stress and reactive oxygen species sensitized immunotherapy, this image-guided nanosystem shows potential for highly specific, effective combined therapy against tumor cells with negligible side-effects to normal cells which will provide a new insight for precise tumor treatment., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Background: Traumatic brain injury (TBI) remains a major concern for global health. Recent studies have suggested the role of NOD-like receptor pyrin domain-containing protein 3 (NLRP3), an inflammatory marker, in the cerebrospinal fluid (CSF) and serum as potential indicators of TBI prognosis. The objective of the study was to characterize NLRP3 as a clinically applicable tool for predicting the outcomes of TBI patients., Methods: A total of 270 patients with moderate to severe TBI were included in this retrospective analysis. Serum and CSF samples were collected at 1-, 3-, 7-, and 21-day post-injury to measure NLRP3 levels. The prognosis of patients was evaluated after 3 months using the Glasgow Outcome Scale (GOS). Patients were categorized into good prognosis (GOS score >3) and poor prognosis (GOS score ≤3) groups. The relationship between NLRP3 levels and prognosis was analyzed., Results: Patients with poor prognosis had significantly elevated NLRP3 levels in their serum on days 1 and 3 post-injury compared with those with a good prognosis. The difference was more pronounced during these early days compared with days 7 and 21. However, NLRP3 levels in CSF consistently showed a large difference between the two groups throughout the observation period. Receiver operating characteristic analysis revealed that the level of NLRP3 in the CSF on day 3 post-injury had the highest predictive value for prognosis, with an area under the curve of 0.83, followed by the level of NLRP3 in the serum on day 3 post-injury., Conclusions: The levels of NLRP3, especially in the CSF on day 3 post-injury, can serve as a potential biomarker for predicting prognosis in moderate to severe TBI patients. Early measurement of NLRP3 levels can provide valuable insights into patient outcomes and guide therapeutic strategies., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Competing Interests: The authors declare that they have no conflict of interest.

Background: Metagenomic next-generation sequencing (mNGS), which provides untargeted and unbiased pathogens detection, has been extensively applied to improve diagnosis of pulmonary infection. This study aimed to compare the clinical performance between mNGS and targeted NGS (tNGS) for microbial detection and identification in bronchoalveolar lavage fluid (BALF) from kidney transplantation recipients (KTRs)., Methods: BALF samples with microbiological results from mNGS and conventional microbiological test (CMT) were included. For tNGS, samples were extracted, amplified by polymerase chain reaction with pathogen-specific primers, and sequenced on an Illumina Nextseq., Results: A total of 99 BALF from 99 KTRs, among which 93 were diagnosed as pulmonary infection, were analyzed. Compared with CMT, both mNGS and tNGS showed higher positive rate and sensitivity (p<0.001) for overall, bacterial and fungal detection. Although the positive rate for mNGS and tNGS was comparable, mNGS significantly outperformed tNGS in sensitivity (100% vs. 93.55%, p<0.05), particularly for bacteria and virus (p<0.001). Moreover, the true positive rate for detected microbes of mNGS was superior over that of tNGS (73.97% vs. 63.15%, p<0.05), and the difference was also significant when specific for bacteria (94.59% vs. 64.81%, p<0.001) and fungi (93.85% vs. 72.58%, p<0.01). Additionally, we found that, unlike most microbes such as SARS-CoV-2, Aspergillus , and EBV, which were predominantly detected from recipients who underwent surgery over 3 years, Torque teno virus (TTV) were principally detected from recipients within 1-year post-transplant, and as post-transplantation time increased, the percentage of TTV positivity declined., Conclusion: Although tNGS was inferior to mNGS owing to lower sensitivity and true positive rate in identifying respiratory pathogens among KTRs, both considerably outperformed CMT., Competing Interests: Authors BH and HX are employed by Vision Medicals Co., Ltd. The remaining 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 Huang, Hu, Li, Feng, Wang, Huang, Xu, Liu and Shang.)

An immunosuppressive tumour microenvironment strongly influences response rates in patients receiving immune checkpoint blockade-based cancer immunotherapies, such as programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1). Here we demonstrate that metal-ion-chelating L-phenylalanine nanostructures synergize with short-term starvation (STS) to remodel the immunosuppressive microenvironment of breast and colorectal tumours. These nanostructures modulate the electrophysiological behaviour of dendritic cells and activate them through the NLRP3 inflammasome and calcium-mediated nuclear factor-κB pathway. STS promotes the cellular uptake of nanostructures through amino acid transporters and plays a key role in dendritic cell maturation and tumour-specific cytotoxic T lymphocyte responses. This study demonstrates the potential role of metal-ion-chelating L-phenylalanine nanostructures in activating immune responses and the effect of STS treatment in improving nanomaterial-mediated cancer immunotherapy., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

We demonstrate that the β-polymorph of zinc dicyanamide, Zn[N(CN) 2 ] 2 , can be efficiently used as a negative electrode material for lithium-ion batteries. Zn[N(CN) 2 ] 2 exhibits an unconventional increased capacity upon cycling with a maximum capacity of about 650 mAh·g -1 after 250 cycles at 0.5C, an increase of almost 250%, and then maintaining a large reversible capacity of more than 600 mAh·g -1 for 150 cycles. Such an increased capacity is primarily attributed to the increased level of activity in the conversion reaction. A combination of conversion-type and alloy-type mechanisms is revealed in this anode material via advanced characterization studies and theoretical calculations. This mechanism, observed here for the first time in transition-metal dicyanamides, is probably responsible for the outstanding electrochemical performance. We believe that this study guides the development of new high-capacity anode materials.

The combined application of manure and mineral fertilizer represents an effective strategy for enhancing crop yield. However, the relationship between soil fertility and crop yield remains unclear in saline-alkaline soil. Here, a 9-year field experiment (2015-2023) was conducted to investigate the effects of manure application and crop rotations on crop yield and economic efficiency as well as potential associated mechanisms in the Hetao Irrigation District. The results showed that in the third cropping rotation cycle, combined application of manure and mineral fertilizers (NPKO) caused a 6.2%, 38.9%, 65.3%, and 132.2% increase in wheat, sunflower, wheat equivalent yield, and the economic income of sunflower, respectively. The average grain yield had a positive correlation with soil organic matter and nutrient supply. This suggested that the soil organic matter had a positive effect on the crop yield due to its impact on nutrient supply. Simultaneously, the sunflower seed setting rate increased by 65.2% under NPKO. The linear regression model revealed that each additional input of 20 Mg ha -1 of manure resulted in an increase of 3.56 kg ha -1 in crop phosphorus harvest and a 0.05 Kg ha -1 increase in wheat equivalent yield compared to NPK. In conclusion, our results highlighted that manure application promotes soil properties and improves crop yield.

Morphing wing technology is crucial for enhancing the flight performance of aircraft. To address the monitoring challenges of full-scale variable-camber leading edges under flight conditions, this study introduces a ground-based strength testing technique aimed at precisely evaluating the deformation patterns and structural strength during actual operation. Firstly, the motion characteristics of the variable-camber leading edge were analyzed using numerical simulation based on kinematic theory. Secondly, a tracking loading test rig was designed and constructed to simulate the actuated deformation and aerodynamic loads of the leading edge. Next, mechanical boundary numerical simulation was then utilized to predict the motion trajectories of loading points on the upper and lower wing surfaces, and a multi-point coordinated control system was developed to achieve accurate experimental control. Finally, a multi-sensor iterative method was employed to ensure loading precision throughout the testing process. A case study was conducted using a leading edge test piece from a specific commercial aircraft. The results indicated that in the motion test of the variable-camber leading edge, the average error of the deflection angle was 4.59%; in the strength test, the average errors in the magnitude and direction of the applied load were 0.54% and 0.24%, respectively. These findings validate the effectiveness of the proposed technique in simulating the flight conditions of deforming wings and accurately obtaining the leading edge shape change curve, deformation accuracy curve, and strain curves of the upper and lower wing surfaces under deflection angles. Furthermore, this paper compares the deformation accuracy of different testing methods under test conditions, providing scientific evidence and technical support for the testing and evaluation of variable-camber leading edges.

Establishing target engagement is fundamental to effective target-based drug development. It paves the way for efficient medicinal chemistry design and definitive answers about target validation in the clinic. For irreversible targeted covalent inhibitor (TCI) drugs, there is a unique opportunity to establish and quantify the target engagement or occupancy. This is typically accomplished by using a covalent molecular probe, often a TCI analogue, derivatized to allow unoccupied target sites to be tracked; the difference of total sites minus unoccupied sites yields the occupied sites. When such probes are not available or the target is not readily accessible to covalent probes, another approach is needed. Receptor tyrosine-protein kinase erbB-2 (HER2) occupancy by afatinib presents such a case. Available HER2 covalent probes were unable to consistently modify HER2 after sample preparation, resulting in inadequate data. We demonstrate an alternative quantitative probe-free occupancy (PFO) method. It employs the immunoprecipitation of HER2 and direct mass spectrometer analysis of the cysteine-containing peptide that is targeted and covalently occupied by afatinib. Nontarget HER2 peptides provide normalization to the total protein. We show that HER2 occupancy by afatinib correlates directly to the inhibition of the receptor tyrosine kinase activity in NCI-N87 cells in culture and in vivo using those cells in a mouse tumor xenograft mode., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Nanomaterials doped with high atom number elements can improve the efficacy of cancer radiotherapy, but their clinical application faces obstacles, such as being difficult to degrade in vivo, or still requiring relatively high radiation dose. In this work, a bismuth oxycarbonate-based ultrathin nanosheet with the thickness of 2.8 nm for safe and efficient tumor radiotherapy under low dose of X-ray irradiation is proposed. The high oxygen content (62.5% at%) and selective exposure of the facets of ultrathin 2D nanostrusctures facilitate the escape of large amounts of oxygen atoms on bismuth nanosheets from surface, forming massive oxygen vacancies and generating reactive oxygen species that explode under the action of X-rays. Moreover, the exposure of almost all atoms to environmental factors and the nature of oxycarbonates makes the nanosheets easily degrade into biocompatible species. In vivo studies demonstrate that nanosheets could induce apoptosis in cancer cells after low dose of X-ray irradiation without causing any damage to the liver or kidney. The tumor growth inhibition effect of radiotherapy increases from 49.88% to 90.76% with the help of bismuth oxycarbonate nanosheets. This work offers a promising future for nanosheet-based clinical radiotherapies of malignant cancers., (© 2024 Wiley‐VCH GmbH.)

Lumbar spinal stenosis (LSS) can cause a range of cauda equina symptoms, including lower back and leg pain, numbness, and intermittent claudication. This disease affects approximately 103 million people worldwide, particularly the elderly, and can seriously compromise their health and well-being. Ligamentum flavum hypertrophy (LFH) is one of the main contributing factors to this disease. Surgical treatment is currently recommended for LSS caused by LFH. For patients who do not meet the criteria for surgery, symptom relief can be achieved by using oral nonsteroidal anti-inflammatory drugs (NSAIDs) and epidural steroid injections. Exercise therapy and needle knife can also help to reduce the effects of mechanical stress. However, the effectiveness of these methods varies, and targeting the delay in LF hypertrophy is challenging. Therefore, further research and development of new drugs is necessary to address this issue. Several new drugs, including cyclopamine and N-acetyl-l-cysteine, are currently undergoing testing and may serve as new treatments for LSS caused by LFH., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The regulation of fruit development is a complex process and a core issue in the fruit tree industry. To investigate the role of PbGIF1 in pear fruit development, we identified a transcription factor PbbHLH137 that regulates pear (Pyrus bretschneideri) fruit development by screening a yeast library constructed from fruit cDNA. Yeast two-hybrid (Y2H), bimolecular fluorescence complementation (BiFC), and split luciferase complementation (split-LUC) assays were performed to confirm the PbbHLH137-PbGIF1 interaction. By tracing the complete fruit development process, we found that PbbHLH137 expression was closely related to fruit size and highly involved at the late pear fruit development stage. Transgenic experiments showed that heterologous expression of PbbHLH137 or PbGIF1 promoted fruit enlargement. PbbHLH137 promoted mainly the expansion of fruit cell volume, whereas PbGIF1 mainly increased the number of cells. Further LUC experiments demonstrated that PbGIF1 promoted the transcriptional activation ability of PbbHLH137. Our work identified PbbHLH137 as a transcription factor that regulates fruit development, and showed that PbGIF1 played an ongoing role during fruit development, making it a candidate gene for genetic improvement of pear fruit development., (© 2024 Scandinavian Plant Physiology Society.)

Metallic biomaterials activate tumor ferroptosis by increasing oxidative stress, but their efficacy is severely limited in tumor microenvironment. Although interferon gamma (IFN-γ) can promote tumor ferroptosis sensitivity by inhibiting the antioxidant system and promoting lipid accumulation, this effect limited by the lack of IFN-γ accumulation in tumors. Herein, we report a near-infrared (NIR)-responsive HCuS nanocomposite (HCuS-PE@TSL-tlyp-1) that can stimulate immunogenic cell death (ICD)-mediated IFN-γ secretion through exogenous oxidative stress, thereby achieving cascaded ferrotherapy by mutually reinforcing ferroptosis and systemic immunity. Upon laser irradiation, the dissolution of the thermal coating, and the introduction of Cu ions and piperazine-erastin (PE) simultaneously induce oxidative stress by reactive oxygen species (ROS)/lipid peroxide (LPO) accumulation and deplete cystine-glutamate transporter (xCT)/GSH. The onset of oxidative stress-mediated ferroptosis is thus achieved, and ICD is triggered, significantly promoting cytotoxic T-cell (CTL) infiltration for IFN-γ secretion. Furthermore, IFN-γ induces immunogenic tumor ferroptosis by inhibiting xCT-antioxidant pathways and enhancing the ACSL4-fatty acid recruitment pathway, which further promotes sensitivity to ferroptosis in cells. These HCuS nanocomposites combined with aPD-L1 effectively in inhibiting tumor metastasis and recurrence. Importantly, these cascade ferrotherapy results broadens the application of HCuS biomaterials., Competing Interests: Declaration of competing interest All authors have given approval to the final version of the manuscript and the authors declare no competing financial interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Soft on-skin electrodes play an important role in wearable technologies, requiring attributes such as wearing comfort, high conductivity, and gas permeability. However, conventional fabrication methods often compromise simplicity, cost-effectiveness, or mechanical resilience. In this study, a mechanically robust and gas-permeable on-skin electrode is presented that incorporates Flash Graphene (FG) integrated with a bioinspired armor design. FG, synthesized through Flash Joule Heating process, offers a small-sized and turbostratic arrangement that is ideal for the assembly of a conductive network with nanopore structures. Screen-printing is used to embed the FG assembly into the framework of polypropylene melt-blown nonwoven fabrics (PPMF), forming a soft on-skin electrode with low sheet resistance (125.2 ± 4.7 Ω/□) and high gas permeability (≈10.08 mg cm⁻ 2 h⁻¹). The "armor" framework ensures enduring mechanical stability through adhesion, washability, and 10,000 cycles of mechanical contact friction tests. Demonstrating capabilities in electrocardiogram (ECG) and electromyogram (EMG) monitoring, along with serving as a self-powered triboelectric sensor, the FG/PPMF electrode holds promise for scalable, high-performance flexible sensing applications, thereby enriching the landscape of integrated wearable technologies., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Thermal stratification and mixing play important roles in the physicochemical composition of lakes and affect the geochemical cycle. However, the regulation of lake carbon exchange at the water-air interface by seasonal thermal structures remains unclear, especially for alpine saline lake on the Qinghai-Tibet Plateau (QTP). Based on continuous field sampling, carbon dioxide flux (FCO 2 ) at the water-air interface in Qinghai Lake during the ice-free period was quantitatively analyzed by thin boundary layer model, as well as the driving factors of the change in FCO 2 at the water-air interface. The findings revealed that the FCO 2 was -22.16 ± 11.73 mmol m -2 d -1 during the stratification period, and - 45.32 ± 29.67 mmol m -2 d -1 during the mixing period. We found that thermal stratification limits the matter-energy exchange between the upper and bottom water columns, and carbonate precipitation results in a higher FCO 2 than during mixing stage. However, the mixing process reduces the limiting effect of thermal stratification. During the carbonate process, water with higher salinity and pH at the bottom of the water column enters the upper part of the water column, reducing the partial pressure of carbon dioxide (pCO 2 ) in the water column and causing the absorption of CO 2 by the lake. Thermal stratification affects the vertical material-energy exchange and atmospheric CO 2 uptake of lake. The present study further explains the possible underlying regulation of CO 2 uptake in saline lake on the QTP involving the varied thermal structure., 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.)

Controlled release drug delivery systems of eye drops are a promising ophthalmic therapy with advantages of good patient compliance and low irritation. However, the lack of a suitable drug carrier for ophthalmic use limits the development of the aforementioned system. Herein, the crosslinked cyclodextrin organic framework (COF) with a cubic porous structure and a uniform particle size was synthesized and applied to solidify vitamin A palmitate (VAP) by using the solvent-free method. The VAP@COF suspension eye drops were formulated by screening co-solvents, suspending agents, and stabilizing agents to achieve a homogeneous state and improve stability. According to the in vitro release study, the VAP@COF suspension exhibited a controlled release of VAP within 12 h. Both the ex vivo corneal contact angle and in vivo fluorescence tracking indicated that the VAP@COF suspension prolonged the VAP residence time on the ocular surface. This suspension accelerated the recovery of the dry eye disease (DED) model in New Zealand rabbits. Furthermore, the suspension was non-cytotoxic to human corneal epithelial cells and non-irritation to rabbit eyes. In summary, the particulate COF is an eye-acceptable novel carrier that sustains release and prolongs the VAP residence time on the ocular surface for DED treatment., 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.)

Photothermal therapy (PTT) is a promising cancer treatment method due to its ability to induce tumor-specific T cell responses and enhance therapeutic outcomes. However, incomplete PTT can leave residual tumors that often lead to new metastases and decreased patient survival in clinical scenarios. This is primarily due to the release of ATP, a damage-associated molecular pattern that quickly transforms into the immunosuppressive metabolite adenosine by CD39, prevalent in the tumor microenvironment, thus promoting tumor immune evasion. This study presents a photothermal nanomedicine fabricated by electrostatic adsorption among the Fe-doped polydiaminopyridine (Fe-PDAP), indocyanine green (ICG), and CD39 inhibitor sodium polyoxotungstate (POM-1). The constructed Fe-PDAP@ICG@POM-1 (FIP) can induce tumor PTT and immunogenic cell death when exposed to a near-infrared laser. Significantly, it can inhibit the ATP-adenosine pathway by dual-directional immunometabolic regulation, resulting in increased ATP levels and decreased adenosine synthesis, which ultimately reverses the immunosuppressive microenvironment and increases the susceptibility of immune checkpoint blockade (aPD-1) therapy. With the aid of aPD-1, the dual-directional immunometabolic regulation strategy mediated by FIP can effectively suppress/eradicate primary and distant tumors and evoke long-term solid immunological memory. This study presents an immunometabolic control strategy to offer a salvage option for treating residual tumors following incomplete PTT., (© 2024. The Author(s).)

Background: Ovarian cancer (OC) is a major global cause of death among gynecological cancers, with a high mortality rate. Early diagnosis, distinguishing between benign conditions and early malignant OC forms, is vital for successful treatment. This research investigates serum metabolites to find diagnostic biomarkers for early OC identification., Methods: Metabolomic profiles derived from the serum of 60 patients with benign conditions and 60 patients with malignant OC were examined using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Comparative analysis revealed differential metabolites linked to OC, aiding biomarker identification for early-diagnosis of OC via machine learning features. The predictive ability of these biomarkers was evaluated against the traditional biomarker, cancer antigen 125 (CA125)., Results: 84 differential metabolites were identified, including 2-Thiothiazolidine-4-carboxylic acid (TTCA), Methionyl-Cysteine, and Citrulline that could serve as potential biomarkers to identify benign conditions and malignant OC. In the diagnosis of early-stage OC, the area under the curve (AUC) for Citrulline was 0.847 (95 % Confidence Interval (CI): 0.719-0.974), compared to 0.770 (95 % CI: 0.596-0.944) for TTCA, and 0.754 for Methionine-Cysteine (95 % CI: 0.589-0.919). These metabolites demonstrate a superior diagnostic capability relative to CA125, which has an AUC of 0.689 (95 % CI: 0.448-0.931). Among these biomarkers, Citrulline stands out as the most promising. Additionally, in the diagnosis of benign conditions and malignant OC, using logistic regression to combine potential biomarkers with CA125 has an AUC of 0.987 (95 % CI: 0.9708-1) has been proven to be more effective than relying solely on the traditional biomarker CA125 with an AUC of 0.933 (95 % CI: 0.870-0.996). Furthermore, among all the differential metabolites, lipid metabolites dominate, significantly impacting glycerophospholipid metabolism pathway., Conclusion: The discovered serum metabolite biomarkers demonstrate excellent diagnostic performance for distinguishing between benign conditions and malignant OC and for early diagnosis of malignant OC., 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.)

Higher-order topological states extend the power of nontrivial topological states beyond the bulk-edge correspondence. Here we study the higher-order topological states (corner states) in an open-boundary two-dimensional T-graphene lattice. Unlike the common zero-energy corner states, our findings reveal non-zero energy corner states in such lattice systems, and the energy could be controlled by modifying the hopping parameters. Moreover, the corner states could be transferred away from the lattice corners by designing the position-specific vacancy defects. The strong robustness of the corner states is also demonstrated against the uniaxial strain and vacancy defects, respectively. A plasmonic crystal is constructed to testify to the theory, in which the corner states are realized in optical modes and their higher-order topological properties are verified. Our results open the avenue of corner-states engineering, which holds significant physical implications of higher-order topological states for the design of photonic and electronic devices with specialized functionalities., (© 2024 IOP Publishing Ltd.)

In recent years, various kinds of civil explosive detonation accidents have occurred frequently around the world, resulting in substantial human casualties and significant property losses. It is generally believed that thermal stimulation plays a critical role in triggering the detonation of explosives; consequently, the study of the thermal hazards of explosives is of great significance to many aspects of safety emergency management practices in the production, transportation, storage, and use of explosives. It is known that the thermal stability of the ammonium perchlorate-aluminium system and the ammonium nitrate-aluminium system has been extensively investigated previously in the literature. However, there is a paucity of research on the thermal hazard characteristics of non-ideal explosives under varying oxygen balance conditions within the academic sphere. Therefore, this research focused on the study of the thermal hazards of non-ideal explosives based on thermokinetic analysis. The thermal hazards of non-ideal explosive mixtures of ammonium perchlorate and aluminium and of ammonium nitrate and aluminium were studied by thermal analysis kinetics. The thermokinetic parameters were meticulously studied through differential scanning calorimetry (DSC) analysis. The results showed that the peak reaction temperature and activation energy of the ammonium perchlorate-aluminium system were significantly higher than those of the ammonium nitrate-aluminium system. Under the condition of zero oxygen balance, the peak reaction temperature of the ammonium nitrate-aluminium system was 259 °C (heating rate 5 °C/min), and the activation energy was 84.7 kJ/mol. Under the same conditions, the peak reaction temperature and activation energy of the ammonium perchlorate-aluminium system were 292 °C (heating rate 5 °C/min) and 94.9 kJ/mol, respectively. These results indicate that the ammonium perchlorate-aluminium system has higher safety under the same thermal stimulation conditions. Furthermore, research on both non-ideal explosive systems reveals that the activation energy is at its peak under negative oxygen balance conditions, recorded at 104.2 kJ/mol (ammonium perchlorate-aluminium) and 86.2 kJ/mol (ammonium nitrate-aluminium), which indicates a higher degree of safety. Therefore, the investigation into the thermal hazards of non-ideal explosive systems under different oxygen balance conditions is of utmost importance for the enhancement and improvement of safety emergency management practices.

With the development of the petroleum industry, the demand for materials for oilfield equipment is becoming increasingly stringent. The strength increase brought about by time strengthening is limited in meeting the needs of equipment development. The GH3625 alloy with different strength levels can be obtained through cold deformation and heat treatment processes. A study should be carried out to further develop the potential mechanical properties of GH3625. In this study, the GH3625 alloy was cold drawn with different reductions in area (0-30%) and heat treated, and its mechanical properties were tested. The microstructure of the alloy during deformation and heat treatment was characterized by methods such as optical microscopy (OM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) based on the principles of physical metallurgy. The strength increase caused by dislocation strengthening was calculated from the dislocation density, tested by X-ray diffraction (XRD). The calculated value was compared to the measured value, elucidating the strengthening effect of cold deformation and heat treatment. The results showed that the yield strength and yield ratio of the cold-drawn alloy significantly reduced after aging at 650 °C and 760 °C. Heat treatment can make a cold-deformed material recover, ablate dislocations, and greatly reduce the dislocation density in the microstructure of the GH3625 alloy, which was the main factor in the decrease in yield strength. The work-hardening gradient of the cold-drawn material varied greatly with different reductions in area. When the reduction in area was small (10%), the hardness gradient was obvious. When it increased to 30%, the alloy was uniformly strengthened as the deformation was transmitted to the axis. This study can provide more mechanical performance options for GH3625 alloy structural components in the petrochemical industry.

Optogenetic, known as the method of 21 centuries, combines optic and genetic engineering to precisely control photosensitive proteins for manipulation of a broad range of cellular functions, such as flux of ions, protein oligomerization and dissociation, cellular intercommunication, and so on. In this technique, light is conventionally delivered to targeted cells through optical fibers or micro light-emitting diodes, always suffering from high invasiveness, wide-field illumination facula, strong absorption, and scattering by nontargeted endogenous substance. Light-transducing nanomaterials with advantages of high spatiotemporal resolution, abundant wireless-excitation manners, and easy functionalization for recognition of specific cells, recently have been widely explored in the field of optogenetics; however, there remain a few challenges to restrain its clinical applications. This review summarized recent progress on light-responsive genetically encoded proteins and the myriad of activation strategies by use of light-transducing nanomaterials and their disease-treatment applications, which is expected for sparking helpful thought to push forward its preclinical and translational uses.

Background: Infliximab, an anti-tumor necrosis factor monoclonal antibody, has revolutionized the pharmacological management of immune-mediated inflammatory diseases (IMIDs). This position statement critically reviews and examines existing data on therapeutic drug monitoring (TDM) of infliximab in patients with IMIDs. It provides a practical guide on implementing TDM in current clinical practices and outlines priority areas for future research., Methods: The endorsing TDM of Biologics and Pharmacometrics Committees of the International Association of TDM and Clinical Toxicology collaborated to create this position statement., Results: Accumulating data support the evidence for TDM of infliximab in the treatment of inflammatory bowel diseases, with limited investigation in other IMIDs. A universal approach to TDM may not fully realize the benefits of improving therapeutic outcomes. Patients at risk for increased infliximab clearance, particularly with a proactive strategy, stand to gain the most from TDM. Personalized exposure targets based on therapeutic goals, patient phenotype, and infliximab administration route are recommended. Rapid assays and home sampling strategies offer flexibility for point-of-care TDM. Ongoing studies on model-informed precision dosing in inflammatory bowel disease will help assess the additional value of precision dosing software tools. Patient education and empowerment, and electronic health record-integrated TDM solutions will facilitate routine TDM implementation. Although optimization of therapeutic effectiveness is a primary focus, the cost-reducing potential of TDM also merits consideration., Conclusions: Successful implementation of TDM for infliximab necessitates interdisciplinary collaboration among clinicians, hospital pharmacists, and (quantitative) clinical pharmacologists to ensure an efficient research trajectory., Competing Interests: Z. Wang is supported by a doctoral research grant from the Research Foundation—Flanders (FWO), Belgium (grant number: 1SF2922N). M. Barclay received consultancy fees from Douglas Pharmaceuticals and Janssen unrelated to submitted work. T. Mizuno served as a consultant of NDA Partners and received speaker honoraria from Astellas Pharma Inc. and Chugai Pharmaceutical Co. R. J. Keizer is an employee and stockholder of InsightRX, a company developing precision dosing software. S. G. Wicha received research grants from Boehringer Ingelheim and AqVida, consulting fees from Merck KGaA and Medicines from Malaria Venture, and speaker honoraria from GlaxoSmithKline. J. Lambert received unrestricted grants from AbbVie, Almirall, Celgene, Eli Lilly, Janssen-Cilag, LEO Pharma, Novartis, and UCB, served as a speaker for AbbVie, Almirall, Bristol-Myers Squibb, Janssen-Cilag, Pfizer, and UCB, and served as a consultant for AbbVie, argenx, Bristol-Myers Squibb, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, LEO Pharma, Novartis, and UCB, with all fees and grants being paid to Ghent University (Hospital) scientific accounts and not to any personal account of Jo Lambert. S. Vermeire received grants from AbbVie, J&J, Pfizer, Galapagos, and Takeda, received consulting and/or speaker fees from AbbVie, AbolerIS Pharma, AgomAb, Alimentiv, Arena Pharmaceuticals, AstraZeneca, Avaxia, BMS, Boehringer Ingelheim, Celgene, CVasThera, Dr Falk Pharma, Ferring, Galapagos, Genentech-Roche, Gilead, GSK, Hospira, Imidomics, Janssen, J&J, Lilly, Materia Prima, MiroBio, Morphic, MRM Health, Mundipharma, MSD, Pfizer, Prodigest, Progenity, Prometheus, Robarts Clinical Trials, Second Genome, Shire, Surrozen, Takeda, Theravance, Tillots Pharma AG, and Zealand Pharma. K. Papamichael received lecture/speaker fees from Physicians Education Resource LLC and Grifols, scientific advisory board fees from ProciseDx Inc. and Scipher Medicine Corporation, and serves as a consultant from Prometheus Laboratories Inc. E. Dreesen received consultancy fees from Alimentiv, argenx, and Prometheus, lecture fees from Galapagos, and financial support from Janssen and Sandoz, outside the submitted work, with all honoraria/fees being paid to KU Leuven and not to any personal account of Erwin Dreesen. D. Alsoud, D. J. A. R. Moes, R. Soenen, Z. Layegh, I. K. Minichmayr, G. Wolbink, A. de Vries, and N. Padullés-Zamora declare that they have no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Numerous studies have investigated the role of collagen type 1 α1 ( COL1A1) polymorphisms in musculoskeletal soft tissue injuries (MSTIs), yielding conflicting results. This study was designed to synthesize existing evidence and clarify the relationship between COL1A1 polymorphisms and MSTI susceptibility. We conducted a comprehensive literature search using PubMed, Cochrane Library, Web of Science, EMBASE, and Wanfang databases. Associations were assessed using odds ratios (ORs) with 95% confidence intervals (95% CIs) across five genetic models. Subgroup analyses were performed based on ethnicity and injury type. Additionally, trial sequential analysis (TSA) was utilized to assess information size and statistical power. We analyzed a total of 16 articles from 358 retrieved studies, encompassing 2094 MSTI cases and 4105 controls. Our pooled data revealed that individuals with the TT genotype of the rs1800012 polymorphism had a significantly reduced risk of MSTIs (TT vs. GG, OR = 0.53, 95% CI 0.35-0.82, P = 0.004; TT vs. TG + GG, OR = 0.54, 95% CI 0.36-0.80, P = 0.002). Ethnicity-based stratification showed a significant association in Caucasians but not Asians. However, no significant association was observed between the rs1107946 polymorphism and MSTIs, regardless of ethnicity or injury type. TSA indicated that the sample sizes may have been insufficient to yield conclusive results. In conclusion, our study supports the protective effect of the TT genotype of the rs1800012 polymorphism against MSTIs, particularly among Caucasians. However, the rs1107946 polymorphism does not appear to influence MSTI susceptibility.

The proton transport in one-dimensional (1D) confined water chains has been extensively studied as a model for ion channels in cell membrane and fuel cell. However, the mechanistic understanding of the proton transfer (PT) process in 1D water chains remains incomplete. In this study, we demonstrate that the two limiting structures of the hydrated excess proton, H5O2+ (Zundel) and H3O+ (linear H7O3+), undergo a change in dominance as the water chain grows, causing two co-existing and opposing PT mechanisms. Specifically, H5O2+ is stable in the middle of the chain, whereas H3O+ serves as a transition state (TS). Except for this region, H3O+ is stabilized while H5O2+ serves as a TS. The interaction analysis shows that the electrostatic interaction plays a crucial role in the difference in PT mechanisms. Our work fills a knowledge gap between the various PT mechanisms reported in bulk water and long 1D water chains, contributing to a deeper understanding of biological ion channels at the atomic level., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: Growth retardation is a common complication of chronic kidney disease in children, which can be partially relieved after renal transplantation. This study aimed to develop and validate a predictive model for growth patterns of children with end-stage renal disease (ESRD) after kidney transplantation using machine learning algorithms based on genomic and clinical variables., Methods: A retrospective cohort of 110 children who received kidney transplants between May 2013 and September 2021 at the First Affiliated Hospital of Zhengzhou University were recruited for whole-exome sequencing (WES), and another 39 children who underwent transplant from October 2021 to March 2022 were enrolled for external validation. Based on previous studies, we comprehensively collected 729 height-related single-nucleotide polymorphisms (SNPs) in exon regions. Seven machine learning algorithms and 10-fold cross-validation analysis were employed for model construction., Results: The 110 children were divided into two groups according to change in height-for-age Z -score. After univariate analysis, age and 19 SNPs were incorporated into the model and validated. The random forest model showed the best prediction efficacy with an accuracy of 0.8125 and an area under curve (AUC) of 0.924, and also performed well in the external validation cohort (accuracy, 0.7949; AUC, 0.796)., Conclusions: A model with good performance for predicting post-transplant growth patterns in children based on SNPs and clinical variables was constructed and validated using machine learning algorithms. The model is expected to guide clinicians in the management of children after renal transplantation, including the use of growth hormone, glucocorticoid withdrawal, and nutritional supplementation, to alleviate growth retardation in children with ESRD., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Leguminous green manure (LGM) has a reputation for improving crop productivity. However, little is known about the beneficial interactions with straw on crop yield and nutrient (N, P, K) use efficiency. Herein, a 9-year field experiment (from 2015 to 2023) containing three treatments-(1) chemical fertilizer as the control (CK), (2) NPK + straw return (Straw) and (3) NPK + straw return with LGM (Straw + LGM)-was conducted to investigate whether the combined application of LGM and straw can increase productivity and nutrient use efficiency in the wheat-maize-sunflower diversified cropping rotation. The results showed that in the third rotation (2021-2023), Straw + LGM significantly increased wheat yield by 10.2% and maize yield by 19.9% compared to CK. The total equivalent yield under Straw + LGM was the highest (26.09 Mg ha -1 ), exceeding Straw and CK treatments by 2.7% and 12.3%, respectively. For each 2 Mg ha -1 increase in straw returned to the field, sunflower yield increased by 0.2 Mg ha -1 , whereas for each 1 Mg ha -1 increase in LGM yield from the previous crop, sunflower yield increased by 0.45 Mg ha -1 . Compared to CK, the co-application of LGM and straw increased the N use efficiency of maize in the first and third rotation cycle by 70.6% and 55.8%, respectively, and the P use efficiency by 147.8% in the third rotation cycle. Moreover, Straw treatment led to an increase of net income from wheat and sunflower by 14.5% and 44.6%, while Straw + LGM increased the net income from maize by 15.8% in the third rotation cycle. Combining leguminous green manure with a diversified cropping rotation has greater potential to improve nutrient use efficiency, crop productivity and net income, which can be recommended as a sustainable agronomic practice in the Hetao District, Northwest China.

In this study, we aimed to evaluate the protective effect of geniposide (GEN) on imiquimod (IMQ)-induced psoriasis-like skin lesions in mice. Firstly, visual changes of psoriatic skin lesions were observed and the severity was recorded using psoriasis area and severity index (PASI) score. Histological changes were assessed by HE staining for epidermal thickness and Masson's staining for collagen fibers. Then, photographs of microvascular inside the skin were taken for macroscopic observation, and microscopic changes associated with angiogenesis were evaluated. Furthermore, expression of angiogenic factors were analyzed by ELISA, immunohistochemistry and immunofluorescence, separately. Lastly, the expression of VEGFR signaling-related proteins was detected by WB. Compared with control, IMQ drove a significant increment of epidermal thicknesses with higher PASI scores and more dermal collagen deposition. IMQ treatment led to abnormal keratinocyte proliferation, increased microvascular inside skin, growing production of angiogenesis-related factors, up-regulated expression of VEGFR1 and VEGFR2, and enhanced phosphorylation of p38. However, GEN significantly ameliorated the psoriatic skin lesions, the epidermal thickness, the formation of collagen fibers, and abnormal keratinocyte proliferation. Importantly, GEN inhibited angiogenesis, the production of angiogenic factors (VEGF-A, Ang-2, TNF-α, and IL-17A), and the proliferation of vascular endothelial cells. Simultaneously, GEN curbed the expression of VEGFR1, VEGFR2, p38, and P-p38 proteins involved in VEGFR signaling. Of note, the suppressive effect of GEN was reversed in the HUVECs with over-expressed VEGFR1 or VEGFR2 related to the cells without transfection. These findings suggest that VEGFR1 and VEGFR2 participate in the anti-angiogenesis of GEN in IMQ-induced psoriasis-like skin lesions in mice., 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.)