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Understanding the molecular mechanism of inhibitor binding to prostate-specific membrane antigen (PSMA) is of fundamental importance for designing targeted drugs for prostate cancer. Here we designed a series of PSMA-targeting inhibitors with distinct molecular structures, which were synthesized and characterized using both experimental and computational approaches. Microsecond molecular dynamics simulations revealed the structural and thermodynamic details of PSMA-inhibitor interactions. Our findings emphasize the pivotal role of the inhibitor's P1 region in modulating binding affinity and selectivity and shed light on the binding-induced conformational shifts of two key loops (the entrance lid and the interface loop). Binding energy calculations demonstrate the enthalpy-entropy balance in the thermodynamic driving force of different inhibitors. The binding of inhibitors in monomeric form is entropy-driven, in which the solvation entropy from the binding-induced water restraints plays a key role, while the binding of inhibitors in dimeric form is enthalpy-driven, due to the promiscuous PSMA-inhibitor interactions. These insights into the molecular driving force of protein-ligand binding offer valuable guidance for rational drug design.

The aim was to examine the diagnostic efficacy of hippocampal subregions volume and texture in differentiating amnestic mild cognitive impairment (MCI) from normal aging changes. Ninety MCI subjects and eighty-eight well-matched healthy controls (HCs) were selected. Twelve hippocampal subregions volume and texture features were extracted using Freesurfer and MaZda based on T1 weighted MRI. Then, two-sample t-test and Least Absolute Shrinkage and Selection Operator (LASSO) regression were developed to select a subset of the original features. Support vector machine (SVM) was used to perform the classification task and the area under the curve (AUC), sensitivity, specificity and accuracy were calculated to evaluate the diagnostic efficacy of the model. The volume features with high discriminative power were mainly located in the bilateral CA1 and CA4, while texture feature were gray-level non-uniformity, run length non-uniformity and fraction. Our model based on hippocampal subregions volume and texture features achieved better classification performance with an AUC of 0.90. The volume and texture of hippocampal subregions can be utilized for the diagnosis of MCI. Moreover, we found that the features that contributed most to the model were mainly textural features, followed by volume. These results may guide future studies using structural scans to classify patients with MCI.

In recent years, targeting mitochondrial apoptosis has emerged as a promising therapeutic strategy for Acute Myeloid Leukemia (AML). The SLC25 family of mitochondrial carriers plays a critical role in maintaining mitochondrial function and regulating apoptosis. However, the role of SLC25A21, an oxodicarboxylate carrier, in AML progression and its potential as a prognostic biomarker remain underexplored. This study aimed to further investigate the role, molecular mechanism, and potential clinical value of SLC25A21 in AML progression. The transcript levels of SLC25A21 in bone marrow specimens were analyzed using real-time quantitative polymerase chain reaction. The correlation between SLC25A21 expression and the prognosis of AML was assessed through survival analysis. Findings revealed that SLC25A21 was downregulated in adult AML, and the low expression of SLC25A21 was correlated with worse prognosis for AML patients. Furthermore, overexpression of SLC25A21 inhibited cell proliferation and cell cycle progression, and was correlated with apoptosis through mitochondrial apoptosis signaling pathway. C-X-C motif chemokine ligand 8 (CXCL8) was identified as a downstream target of SLC25A21. These functions of SLC25A21 could be rescued by the overexpression of CXCL8. Moreover, SLC25A21 overexpression significantly suppressed the growth of xenograft tumors. In conclusion, the low SLC25A21 expression is correlated with poor clinical outcome. The overexpression of SLC25A21 inhibited the AML cell survival and proliferation by dysregulating the expression of CXCL8. SLC25A21 might be a potential prognostic marker and a treatment target for AML., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All procedures involving human specimens were performed in accordance with the guidelines and regulations of the Ethics Committee of the First Affiliated Hospital of Zhengzhou University [2022-KY- 0120-003]. Informed consent was obtained from all patients according to the Declaration of Helsinki. All animal experiments were conducted in accordance with the institutional guidelines and were approved by the Laboratory Animal Center of Zhengzhou University [ZZU-LAC20230526 [35]]., (© 2024. The Author(s).)

Osteoarthritis (OA) is recognized as a highly friction-related joint disease primarily associated with increased joint friction and inflammation due to pro-inflammatory M1-type macrophage infiltration in the articular cavity. Therefore, strategies to simultaneously increase lubrication and relieve inflammation to remodel the damaged articular microenvironment are of great significance for enhancing its treatment. Herein, a multifunctional core-brush nanoplatform composed of a ROS-scavenging polydopamine-coated SiO 2 core and lubrication-enhancing zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) brush and loaded with the anti-inflammatory drug curcumin by a reactive oxygen species (ROS)-liable conjugation (named as SiO 2 @PP-Cur) is rationally designed. Benefiting from the grafted zwitterionic PMPC brush, a tenacious hydration layer with enhanced lubricity for reducing joint abrasions is developed. More importantly, based on the mono-iodoacetic acid-induced arthritis (MIA) rat model, intra-articular injection of SiO 2 @PP-Cur nanoplatform can effectively alleviate articular inflammation via promoting macrophage polarization from the pro-inflammatory M1 to anti-inflammatory M2 state by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and attenuating the degradation of cartilage matrix, resulting in the remodeling of the damaged microenvironment into a pro-regenerative microenvironment. As a result, SiO 2 @PP-Cur can considerably inhibit OA progression. Therefore, the work may provide a novel strategy for the development of an advanced core-brush nanoplatform for enhanced OA therapy., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Targeting Heat shock protein 90 (HSP90) C-terminus is an important strategy to develop HSP90 inhibitors without inducing heat shock response. The development of C-terminal inhibitors, however, is hampered by a lack of understanding regarding the interaction between the HSP90 C-terminus and the present inhibitors. We collected seven classical and structurally diverse HSP90 C-terminal inhibitors and constructed a ligand-based pharmacophore model. The subsequent virtual screening and structural optimisation led to the identification of 2-heteroarylthio- N -arylacetamides as novel HSP90 C-terminal inhibitors. 9 and 27 exhibited strong antitumour activity in vitro by inhibiting proliferation and inducing apoptosis in multiple cancer cell lines. These compounds disrupted the interaction between HSP90 C-terminus and peptidylprolyl isomerase D, exerting a stronger inhibitory effect than novobiocin. 27 significantly induced the degradation of HSP90 clients without triggering heat shock response. In an in vivo study using 4T1 mice breast cancer models, 9 showed a potent antitumour effect without obvious toxicity.

Owing to their inherent flexibility and excellent biocompatibility, liquid metals (LMs) have been explored at the frontiers of clinical therapy. Herein, a LM and tanshinone IIA (TA) drugs were dispersed into sodium alginate (SA) solution by ultrasonication to prepare SA/LM/TA, which is an injectable biomaterial for stable drug release and intrapericardial injection for the treatment of myocardial infarction (MI). The SA/LM/TA has a low viscosity and can be injected smoothly using a syringe. In rat models of MI, we demonstrated that SA/LM/TA injection in the pericardial cavity is a biosafe and effective method to deliver a carrier containing LM particles and TA drugs for MI treatment. After injection, the drug release is slow and stable in the pericardial cavity, increasing the cardiac retention of drugs. After surgery and treatment for 7 days, the cardiac function of rats improved compared with the control group and the TA direct injection group. The intrapericardial injection of SA/LM/TA improves cardiac functions and mitigates cardiac remodeling post myocardial infarction of rats. Overall, the present study establishes a therapeutic strategy for treatment of myocardial infarction by intrapericardial injection of SA/LM/TA and expands the application categories of LM biomaterials in disease treatments.

The aim of this study is to investigate the correlation between soft drusen and the likelihood of mortality from all causes and specific ailments within a representative United States population. This cohort study encompassed 4497 individuals from the 2005 to 2008 National Health and Nutrition Examination Survey (NHANES) cycles, and followed for survival to December 31, 2019. Data on soft drusen were obtained from fundus images. Survey-weighted Cox regression models were utilized to evaluate the hazard of soft drusen incidence and mortality. After a median follow-up of 12.33 (11.33, 12.58) years, 1014 (22.5%) patients died from all causes. Overall, individuals with soft drusen exhibited an increased risk for all-cause mortality (HR 1.41; 95% CI 1.22 to 1.64), cardiovascular disease (CVD)-related death (HR 1.53; 95% CI 1.15 to 2.04), and mortality from other causes (HR 1.48; 95% CI 1.20 to 1.83). Further stratified analysis revealed that the mortality rates were heightened in participants who had distinct soft drusen or both types of soft drusen, as well as those with soft drusen measuring 500 μm or more in diameter. The investigation revealed that soft drusen was linked to all-cause mortality, CVD mortality, and mortality resulting from non-cardiovascular and non-cancerous conditions, indicating that soft drusen may symbolize frailty and aging processes., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Previous studies have indicated potential associations between metals, lifestyle factors, and sarcopenia. However, the specific causal relationships between iron status, lifestyle factors, and sarcopenia remain unclear. Therefore, we conducted a bidirectional two-sample Mendelian Randomization (MR) approach to investigate these relationships., Methods: The exposure variables included iron status, living alone, coffee intake, alcohol taken with meals, and moderate physical activity, while the outcome variable was sarcopenia, assessed by grip strength in both hands and usual walking pace. We employed the Weighted Median (WM), the Inverse Variance-Weighted (IVW), and other MR methods to explore these problems for analysis. Simultaneously, we conducted a bidirectional MR analysis to assess whether sarcopenia has a reverse causal relationship with internal iron status., Results: In our present research, we found serum iron (P = 0.033), ferritin (P = 0.001), transferrin saturation (P = 0.029) and coffee intake (P = 0.002) revealed a negative trend for sarcopenia, living alone (P = 0.022) and alcohol taken with meal (P = 0.006) showed a opposite trend for sarcopenia. Whereas sarcopenia showed negative trend for ferritin (P = 0.041) and transferrin saturation (P = 0.043), showed the opposite trend for transferrin (P = 0.021)., Conclusion: Our study suggested that higher serum iron levels might reduce the risk of sarcopenia. Moreover, living alone and alcohol consumption might increase the sarcopenia risk, while coffee intake and moderate physical activity could reduce the sarcopenia risk., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Osteoarthritis (OA) is a chronic joint disease highly associated with an imbalance in the network of inflammatory factors and typically characterized by oxidative stress and cartilage damage. Moreover, the specificity of the joint structure makes it difficult for drugs to achieve good penetration and effective enrichment in the joint cavity. Therefore, therapeutic strategies that increase the specific targeting of drugs to inflammatory joint and incorporate antioxidative stress effects are important to improve the efficacy of OA. Here, we developed a folic acid-modified liposomal nanoparticle (AST@Lip-FA) loaded with the antioxidant astaxanthin (AST) to enhance the water solubility and stability of AST and to target the delivery of AST to the site of OA, leading to a significant improvement in therapeutic efficacy. In vitro experiments demonstrated that, due to the recognition by FA of the receptor folate receptor β on the surface of activated macrophages, the cellular uptake efficiency of AST@Lip-FA was increased. Meanwhile, intracellularly overexpressed inflammatory mediators such as reactive oxygen species and nitric oxide were efficiently removed by AST@Lip-FA. In addition, in the ACLT-induced OA mouse model, AST@Lip-FA was precisely enriched in the inflamed joints and achieved long-term retention, fully utilizing the anti-inflammatory, antioxidant, and cartilage-protecting effects of AST to effectively alleviate the progression of OA. In summary, AST@Lip-FA has an important prospect as a potential and effective therapeutic strategy for OA.

Although the knee joint (KNJ) and temporomandibular joint (TMJ) all belong to the synovial joint, there are many differences in developmental origin, joint structure and articular cartilage type. Studies of joint development in embryos have been performed, mainly using poultry and rodents. However, KNJ and TMJ in poultry and rodents differ from those in humans in several ways. Very little work has been done on the embryonic development of KNJ and TMJ in large mammals. Several studies have shown that pigs are ideal animals for embryonic development research. Embryonic day 30 (E30), E35, E45, E55, E75, E90, Postnatal day 0 (P0) and Postnatal day 30 (P30) embryos/fetuses from the pigs were used for this study. The results showed that KNJ develops earlier than TMJ. Only one mesenchymal condensate of KNJ is formed on E30, while two mesenchymal condensates of TMJ are present on E35. All structures of KNJ and TMJ were formed on E45. The growth plate of KNJ begins to develop on E45 and becomes more pronounced from E55 to P30. From E75 to E90, more and more vascular-rich cartilage canals form in the cartilage regions of both joints. The cartilaginous canal of the TMJ divides the condyle into sections along the longitudinal axis of the condyle. This arrangement of cartilaginous canal was not found in the KNJ. The chondrification of KNJ precedes that of TMJ. Ossification of the knee condyle occurs gradually from the middle to the periphery, while that of the TMJ occurs gradually from the base of the mandibular condyle. In the KNJ, the ossification of the articular condyle is evident from P0 to P30, and the growth plate is completely formed on P30. In the TMJ, the cartilage layer of condyle becomes thinner from P0 to P30. There is no growth plate formation in TMJ during its entire development. There is no growth plate formation in the TMJ throughout its development. The condyle may be the developmental center of the TMJ. The chondrocytes and hypertrophic chondrocytes of the growth plate are densely arranged. The condylar chondrocytes of TMJ are scattered, while the hypertrophic chondrocytes are arranged. Embryonic development of KNJ and TMJ in pigs is an important bridge for translating the results of rodent studies to medical applications.

The enormous data and computational resources required by Convolutional Neural Networks (CNNs) hinder the practical application on mobile devices. To solve this restrictive problem, filter pruning has become one of the practical approaches. At present, most existing pruning methods are currently developed and practiced with respect to the spatial domain, which ignores the potential interconnections in the model structure and the decentralized distribution of image energy in the spatial domain. The image frequency domain transform method can remove the correlation between image pixels and concentrate the image energy distribution, which results in lossy compression of images. In this study, we find that the frequency domain transform method is also applicable to the feature maps of CNNs. The filter pruning via wavelet transform (WT) is proposed in this paper (FPWT), which combines the frequency domain information of WT with the output feature map to more obviously find the correlation between feature maps and make the energy into a relatively concentrated distribution in the frequency domain. Moreover, the importance score of each feature map is calculated by the cosine similarity and the energy-weighted coefficients of the high and low frequency components, and prune the filter based on its importance score. Experiments on two image classification datasets validate the effectiveness of FPWT. For ResNet-110 on CIFAR-10, FPWT reduces FLOPs and parameters by more than 60.0 % with 0.53 % accuracy improvement. For ResNet-50 on ImageNet, FPWT reduces FLOPs by 53.8 % and removes parameters by 49.7 % with only 0.97 % loss of Top-1 accuracy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Root exudates play a pivotal role in shaping the microbial community in the rhizosphere and can impact the efficacy of bacteria in controlling nematode populations. This study identified Proteus vulgaris BX-1 as significantly effective in controlling Meloidogyne incognita . The infection of tomato plants with this nematode induced noticeable alterations in the composition of tomato root exudates and led to an increased colonization rate of strain BX-1. Further investigation into how strain BX-1 responded to changes in tomato root exudates revealed that specific metabolites, such as caffeic acid, coumarin, salicylic acid, sebacic acid, and butyric acid, strongly attracted strain BX-1. This attraction potentially contributed to its enhanced colonization and improved efficiency in controlling nematodes. Understanding the correlation between specific metabolites in root exudates and the response of antagonistic bacteria provides valuable insights for enhancing their effectiveness as biological control agents against plant-parasitic nematodes.

Objective: To investigate short-term effectiveness of robot-guided femoral neck system (FNS) combined with cannulated compression screw (CCS) fixation in treatment of femoral neck fracture in young and middle-aged patients., Methods: A clinical data of 49 young and middle-aged patients with femoral neck fractures, who met the selection criteria and admitted between January 2021 and June 2023, was retrospectively analyzed. After reduction of femoral neck fractures, 27 cases were treated with robot-guided FNS fixation (FNS group) and 22 cases with robot-guided FNS and CCS fixation (FNS+CCS group). There was no significant difference in baseline data such as gender, age, cause of fracture, time from fracture to operation, fracture side, and classification (Garden classification and Pauwels classification) between the two groups ( P >0.05). The operation time, intraoperative blood loss, intraoperative fluoroscopy frequency, the time when the patient began bearing weight, and hip joint pain and functional scores (VAS score and Harris score) at last follow-up for two groups were recorded. Imaging re-examination was taken to evaluate the quality of fracture reduction, fracture healing, as well as the occurrence of fracture non-union, osteonecrosis of the femoral head, and femoral neck shortening., Results: All operations were successfully completed and the incisions healed by first intention. There was no significant difference in operation time and intraoperative blood loss between the two groups ( P >0.05), and the intraoperative fluoroscopy frequency in FNS+CCS group significantly increased compared to FNS group ( P <0.05). All patients were followed up 12-18 months (mean, 14.1 months). Imaging re-examination showed that there was no significant difference in fracture reduction quality between the two groups ( P >0.05), but the fracture healing time was significantly shorter in FNS+CCS group than in FNS group, and weight-bearing began earlier ( P <0.05). The incidences of femoral neck shortening, fracture non-union, and osteonecrosis of the femoral head were lower in FNS+CCS group than in FNS group, and there was significant difference in the incidence of femoral neck shortening between groups ( P <0.05). At last follow-up, there was no significant difference in VAS scores between the two groups ( P >0.05). However, the Harris score was significantly higher in FNS+CCS group than in FNS group ( P <0.05)., Conclusion: Compared with FNS fixation alone, robot-guided FNS combined with CCS fixation in the treatment of femoral neck fractures in young and middle-aged patients has obvious advantages in terms of early weight bearing and fracture healing, improves fracture healing rate, effectively prevents postoperative complications, and can obtain good short-term effectiveness.

Bioluminescence of bacteria is widely applied in biological imaging, environmental toxicant detection, and many other situations. Understanding the spectral tuning mechanism not only helps explain the diversity of colors observed in nature but also provides principles for bioengineering new color variants for practical applications. In this study, time-dependent density functional theory (TD-DFT) and quantum mechanics and molecular mechanics (QM/MM) calculations have been employed to understand the fluorescence spectral tuning mechanism of bacterial luciferase with a focus on the electrostatic effect. The spectrum can be tuned by both a homogeneous dielectric environment and oriented external electric fields (OEEFs). Increasing the solvent polarity leads to a redshift of the fluorescence emission maximum, λ F , accompanied by a substantial increase in density. In contrast, applying an OEEF along the long axis of the isoalloxazine ring ( X -axis) leads to a significant red- or blue-shift in λ F , depending on the direction of the OEEF, yet with much smaller changes in intensity. The effect of polar solvents is directionless, and the red-shifts can be attributed to the larger dipole moment of the S 1 state compared with that of the S 0 state. However, the effect of OEEFs directly correlates with the difference dipole moment between the S 1 and S 0 states, which is directional and is determined by the charge redistribution upon deexcitation. Moreover, the electrostatic effect of bacterial luciferase is in line with the presence of an internal electric field (IEF) pointing in the negative X direction. Finally, the key residues that contribute to this IEF and strategies for modulating the spectrum through site-directed point mutations are discussed.

The association of short-term ambient air pollution exposure with osteoarthritis (OA) outpatient visits has been unclear and no study has assessed the modifying roles of district-level characteristics in the association between ambient air pollution exposure and OA outpatient visits. We investigated the cumulative associations of ambient air pollution exposure with daily OA outpatient visits and vulnerable factors influencing the associations using data from 16 districts of Beijing, China during 2013-2019. A total of 18,351,795 OA outpatient visits were included in the analyses. An increase of 10 μg/m 3 in fine particulate matter (PM 2.5 ), inhalable particulate matter (PM 10 ), nitrogen dioxide (NO 2 ), sulfur dioxide (SO 2 ), maximum 8-hour moving-average ozone (8 h-O 3 ), and 0.1 mg/m 3 in carbon monoxide (CO) at representative lag days were associated with significant increases of 0.31 %, 0.06 %, 0.77 %, 0.87 %, 0.30 %, and 0.48 % in daily OA outpatient visits, respectively. Considerable OA outpatient visits were attributable to short-term ambient air pollution exposure. In addition, low temperature and high humidity aggravated ambient air pollution associated OA outpatient visits. District-level characteristics, such as population density, green coverage rate, and urbanization rate modified the risk of OA outpatient visits associated with air pollution exposure. These findings highlight the significance of controlling ambient air pollution during the urbanization process, which is useful in policy formation and implementation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

In cyanobacteria, Elongation factor Tu (EF-Tu) plays a crucial role in the repair of photosystem II (PSII), which is highly susceptible to oxidative stress induced by light exposure and regulated by reactive oxygen species (ROS). However, the specific molecular mechanism governing the functional regulation of EF-Tu by ROS remains unclear. Previous research has shown that a mutated EF-Tu, where C82 is substituted with a Ser residue, can alleviate photoinhibition, highlighting the important role of C82 in EF-Tu photosensitivity. In this study, we elucidated how ROS deactivate EF-Tu by examining the crystal structures of EF-Tu in both wild-type and mutated form (C82S) individually at resolutions of 1.7 Å and 2.0 Å in Synechococcus elongatus PCC 7942 complexed with GDP. Specifically, the GDP-bound form of EF-Tu adopts an open conformation with C82 located internally, making it resistant to oxidation. Coordinated conformational changes in switches I and II create a tunnel that positions C82 for ROS interaction, revealing the vulnerability of the closed conformation of EF-Tu to oxidation. An analysis of these two structures reveals that the precise spatial arrangement of C82 plays a crucial role in modulating EF-Tu's response to ROS, serving as a regulatory element that governs photosynthetic biosynthesis., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study analyzed the application effect of remimazolam besylate combined with sufentanil on percutaneous vertebroplasty (PVP). Forty elderly patients with osteoporotic vertebral compression fractures (OVCF) were randomly divided into sufentanil (A group) and remimazolam besylate + sufentanil groups (B group). A group was given sufentanil anesthesia, B group was given remimazolam besylate combined with sufentanil anesthesia. Heart rate (HR), mean arterial pressure (MAP), saturation of pulse oxygen (SpO2) and Ramsay sedation score were recorded at different time points, including T0 (before administration), T1 (beginning of surgery), T2 (perfusion of bone cement) and T3 (end of surgery). HR, MAP, SpO2 were continuously monitored by electrocardiogram monitor. The visual analogue scale (VAS) pain scores of the two groups were recorded at before anesthesia and immediately after surgery. The adverse reactions (AR) were observed, including respiratory depression, nausea and vomiting, and restlessness during the recovery period. Compared with group A, MAP was increased at T2 and T3 time points in group B. Ramsay sedation scores at T2 time points in group B were higher than that in group A. The VAS score of immediately after operation and incidence of AR of group B was lower than that of group A. In elderly patients undergoing PVP, remimazolam besylate combined with sufentanil has no obvious effect on patients' respiratory parameters, with clear analgesic and sedative effects and low incidence of AR, which is worthy of promotion.

In vivo bioimaging using shortwave infrared (SWIR) (1000-2000 nm) molecular dyes enables deeper penetration and higher contrast compared to visible and near-infrared-I (NIR-I, 700-900 nm) dyes. Developing new SWIR molecules is still quite challenging. This study developed SRHCYs , a panel of fluorescent dyes based on hemicyanine, with adjustable absorbance (830-1144 nm) and emission (886-1217 nm) wavelength. The photophysical attributes of these dyes are precisely tailored by strengthening the donor parts and extending polymethine chains. SRHCY-3 , with its clickable azido group, was chosen for high-performance imaging of blood vessels in living mice, enabling the precise detection of brain and lung cancer. The combination of these probes achieved in vivo multicolor imaging with negligible optical crosstalk. This report presents a series of SWIR hemicyanine dyes with promising spectroscopic properties for high-contrast bioimaging and multiplexing detection.

PIWI-interacting RNAs (piRNAs) are a typical class of small non-coding RNAs, which are essential for gene regulation, genome stability and so on. Accumulating studies have revealed that piRNAs have significant potential as biomarkers and therapeutic targets for a variety of diseases. However current computational methods face the challenge in effectively capturing piRNA-disease associations (PDAs) from limited data. In this study, we propose a novel method, MRDPDA, for predicting PDAs based on limited data from multiple sources. Specifically, MRDPDA integrates a deep factorization machine (deepFM) model with regularizations derived from multiple yet limited datasets, utilizing separate Laplacians instead of a simple average similarity network. Moreover, a unified objective function to combine embedding loss about similarities is proposed to ensure that the embedding is suitable for the prediction task. In addition, a balanced benchmark dataset based on piRPheno is constructed and a deep autoencoder is applied for creating reliable negative set from the unlabeled dataset. Compared with three latest methods, MRDPDA achieves the best performance on the pirpheno dataset in terms of the five-fold cross validation test and independent test set, and case studies further demonstrate the effectiveness of MRDPDA., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: The present study aimed to investigate the relationship between swollen limb circumference and compartment pressure after a snakebite and to evaluate the diagnostic value of the circumference difference between the healthy and affected sides and the circumference growth rate for snake venom-induced compartment syndrome (CS)., Method: The study was based on a prospective cohort study of snakebite patients at the emergency department of West China Hospital from May 2021 to October 2022. The snakebite patients were divided into the CS and non-compartment syndrome (NCS) groups. The diagnostic value of the circumference of the swollen limb for the CS after snakebite was evaluated using a receiver-operating characteristic curve analysis, and the cut-off value of the circumference of the swollen limb for CS after snakebite was calculated with sensitivity and specificity., Result: The present study enrolled 115 patients with severely swollen limbs after snakebite. The mean age was 59.1 ± 13.6 years, with 58 (50.4 %) female cases and 57 (49.6 %) male cases. There were 33 (28.7 %) cases where the upper limbs were injured and 82 (71.3 %) cases where the lower limbs were injured. These patients were divided into CS (n = 19) and NCS (n = 96) groups. The area under the curve (AUC) for the 15 cm circumference difference and circumferential growth rate of the upper edge of the patella was 0.683 (95 % CI 0.508 to 0.858, P = 0.037), and 0.685 (95 % CI 0.512 to 0.858, P = 0.035). The optimal cut-off values for the 15 cm circumference difference and circumferential growth rate of the upper edge of the patella to distinguish CS and NCS were 2.8 cm (sensitivity = 76.9 %, specificity = 66.7 %) and 7 % (sensitivity = 76.9 %, specificity = 66.7 %), respectively., Conclusion: Limb circumference measurement is a non-invasive, convenient, effective, and repeatable bedside test that can assist clinicians in the early detection of suspected snake venom-induced CS in patients exhibiting limb swelling after snake bites., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Long non-coding RNAs (lncRNAs) are RNA transcripts of more than 200 nucleotides that do not encode canonical proteins. Their biological structure is similar to messenger RNAs (mRNAs). To distinguish between lncRNA and mRNA transcripts quickly and accurately, we upgraded the PLEK alignment-free tool to its next version, PLEKv2, and constructed models tailored for both animals and plants., Results: PLEKv2 can achieve 98.7% prediction accuracy for human datasets. Compared with classical tools and deep learning-based models, this is 8.1%, 3.7%, 16.6%, 1.4%, 4.9%, and 48.9% higher than CPC2, CNCI, Wen et al.'s CNN, LncADeep, PLEK, and NcResNet, respectively. The accuracy of PLEKv2 was > 90% for cross-species prediction. PLEKv2 is more effective and robust than CPC2, CNCI, LncADeep, PLEK, and NcResNet for primate datasets (including chimpanzees, macaques, and gorillas). Moreover, PLEKv2 is not only suitable for non-human primates that are closely related to humans, but can also predict the coding ability of RNA sequences in plants such as Arabidopsis., Conclusions: The experimental results illustrate that the model constructed by PLEKv2 can distinguish lncRNAs and mRNAs better than PLEK. The PLEKv2 software is freely available at https://sourceforge.net/projects/plek2/ ., (© 2024. The Author(s).)

Hydrolyzable tannins (HTs), a class of polyphenolic compounds found in dicotyledonous plants, are widely used in food and pharmaceutical industries because of their beneficial effects on human health. Although the biosynthesis of simple HTs has been verified at the enzymatic level, relevant genes have not yet been identified. Here, based on the parent ion-fragment ion pairs in the feature fragment data obtained using UPLC-Q-TOF-/MS/MS, galloyl phenolic compounds in the leaves of Camellia sinensis and C. oleifera were analyzed qualitatively and quantitatively. Correlation analysis between the transcript abundance of serine carboxypeptidase-like acyltransferases (SCPL-ATs) and the peak area of galloyl products in Camellia species showed that SCPL3 expression was highly correlated with HT biosynthesis. Enzymatic verification of the recombinant protein showed that CoSCPL3 from C. oleifera catalyzed the four consecutive steps involved in the conversion of digalloylglucose to pentagalloylglucose. We also identified the residues affecting the enzymatic activity of CoSCPL3 and determined that SCPL-AT catalyzes the synthesis of galloyl glycosides. The findings of this study provide a target gene for germplasm innovation of important cash crops that are rich in HTs, such as C. oleifera, strawberry, and walnut., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Robust object detection in complex environments, poor visual conditions, and open scenarios presents significant technical challenges in autonomous driving. These challenges necessitate the development of advanced fusion methods for millimeter-wave (mmWave) radar point cloud data and visual images. To address these issues, this paper proposes a radar-camera robust fusion network (RCRFNet), which leverages self-supervised learning and open-set recognition to effectively utilise the complementary information from both sensors. Specifically, the network uses matched radar-camera data through a frustum association approach to generate self-supervised signals, enhancing network training. The integration of global and local depth consistencies between radar point clouds and visual images, along with image features, helps construct object class confidence levels for detecting unknown targets. Additionally, these techniques are combined with a multi-layer feature extraction backbone and a multimodal feature detection head to achieve robust object detection. Experiments on the nuScenes public dataset demonstrate that RCRFNet outperforms state-of-the-art (SOTA) methods, particularly in conditions of low visual visibility and when detecting unknown class objects.

Septins can function as scaffolds for protein recruitment, membrane-bound diffusion barriers, or membrane curvature sensors. Septins are important for cytokinesis, but their exact roles are still obscure. In fission yeast, four septins (Spn1 to Spn4) accumulate at the rim of the division plane as rings. The octameric exocyst complex, which tethers exocytic vesicles to the plasma membrane, exhibits a similar localization and is essential for plasma membrane deposition during cytokinesis. Without septins, the exocyst spreads across the division plane but absent from the rim during septum formation. These results suggest that septins and the exocyst physically interact for proper localization. Indeed, we predicted six pairs of direct interactions between septin and exocyst subunits by AlphaFold2 ColabFold, most of them are confirmed by co-immunoprecipitation and yeast two-hybrid assays. Exocyst mislocalization results in mistargeting of secretory vesicles and their cargos, which leads to cell-separation delay in septin mutants. Our results indicate that septins guide the targeting of exocyst complex on the plasma membrane for vesicle tethering during cytokinesis through direct physical interactions., Competing Interests: Competing Interest The authors declare no competing interest.

Diabetic osteoporosis (DO) presents significant clinical challenges. This study aimed to investigate the potential of magnetic nanoparticle-enhanced extracellular vesicles (GMNP E -EVs) derived from bone marrow mesenchymal stem cells (BMSCs) to deliver miR-15b-5p, thereby targeting and downregulating glial fibrillary acidic protein (GFAP) expression in rat DO models. Data was sourced from DO-related RNA-seq datasets combined with GEO and GeneCards databases. Rat primary BMSCs, bone marrow-derived macrophages (BMMs), and osteoclasts were isolated and cultured. EVs were separated, and GMNP E targeting EVs were synthesized. Bioinformatic analysis revealed a high GFAP expression in DO-related RNA-seq and GSE26168 datasets for disease models. Experimental results confirmed elevated GFAP in rat DO bone tissues, promoting osteoclast differentiation. miR-15b-5p was identified as a GFAP inhibitor, but was significantly downregulated in DO and enriched in BMSC-derived EVs. In vitro experiments showed that GMNP E -EVs could transfer miR-15b-5p to osteoclasts, downregulating GFAP and inhibiting osteoclast differentiation. In vivo tests confirmed the therapeutic potential of this approach in alleviating rat DO. Collectively, GMNP E -EVs can effectively deliver miR-15b-5p to osteoclasts, downregulating GFAP expression, and hence, offering a therapeutic strategy for rat DO., (© 2024. The Author(s).)

Gastrointestinal (GI) cancers are a major global health burden, representing 20% of all cancer diagnoses and 22.5% of global cancer-related deaths. Their aggressive nature and resistance to treatment pose a significant challenge, with late-stage survival rates below 15% at five years. Therefore, there is an urgent need to delve deeper into the mechanisms of gastrointestinal cancer progression and optimize treatment strategies. Increasing evidence highlights the active involvement of abnormal arachidonic acid (AA) metabolism in various cancers. AA is a fatty acid mainly metabolized into diverse bioactive compounds by three enzymes: cyclooxygenase, lipoxygenase, and cytochrome P450 enzymes. Abnormal AA metabolism and altered levels of its metabolites may play a pivotal role in the development of GI cancers. However, the underlying mechanisms remain unclear. This review highlights a unique perspective by focusing on the abnormal metabolism of AA and its involvement in GI cancers. We summarize the latest advancements in understanding AA metabolism in GI cancers, outlining changes in AA levels and their potential role in liver, colorectal, pancreatic, esophageal, gastric, and gallbladder cancers. Moreover, we also explore the potential of targeting abnormal AA metabolism for future therapies, considering the current need to explore AA metabolism in GI cancers and outlining promising avenues for further research. Ultimately, such investigations aim to improve treatment options for patients with GI cancers and pave the way for better cancer management in this area., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: We analyzed quantitative computed tomography (CT) and chemical shift-encoded magnetic resonance imaging (MRI) data from a Chinese cohort to investigate the effects of BMI and aging on different adipose tissue (AT) depots., Methods: In 400 healthy, community-dwelling individuals aged 22 to 83 years, we used MRI to quantify proton density fat fraction (PDFF) of the lumbar spine (L2-L4) bone marrow AT (BMAT), the psoas major and erector spinae (ES) muscles, and the liver. Abdominal total AT, visceral AT (VAT), and subcutaneous AT (SAT) areas were measured at the L2-L3 level using quantitative CT. Partial correlation analysis was used to evaluate the relationship of each AT variable with age and BMI. Multiple linear regression analysis was performed in which each AT variable was evaluated in turn as a function of age and the other five independent AT measurements., Results: Of the 168 men, 29% had normal BMI (<24.0 kg/m 2 ), 47% had overweight (24.0-27.9 kg/m 2 ), and 24% had obesity (≥ 28.0 kg/m 2 ). In the 232 women, the percentages were 46%, 32%, and 22%, respectively. Strong or very strong correlations with BMI were found for total AT, VAT, and SAT in both sexes. BMAT and ES PDFF was strongly correlated with age in women and moderately correlated in men. In both sexes, BMAT PDFF correlated only with age and not with any of the other AT depots. Psoas PDFF correlated only with ES PDFF and not with age or the other AT depots. Liver PDFF correlated with BMI and VAT and weakly with SAT in men. VAT and SAT correlated with age and each other in both sexes., Conclusions: Age and BMI are both associated with adiposity, but their effects differ depending on the type of AT., (© 2024 The Obesity Society.)

Rationale and Objectives: The paravertebral muscles, characterized by their susceptibility to severe size loss and fat infiltration in old age, lack established reference values for age-related variations in muscle parameters. This study aims to fill this gap by establishing reference values for paravertebral muscles in a Chinese adult population., Materials and Methods: This cross-sectional study utilized the baseline data from the prospective cohort China Action on Spine and Hip (CASH). A total of 4305 community-dwelling participants aged 21-80 years in China were recruited between 2013 and 2017. Pregnant women, individuals with metal implants, limited mobility or diseases/conditions (spinal tumor, infection, etc.) affecting lumbar vertebra were excluded from the study. Psoas and paraspinal muscles were measured in quantitative computed tomography (QCT) images at the L3 and L5 levels using Osirix software. Age-related reference values for muscle area, density, and fat fraction were constructed as percentile charts using the lambda-mu-sigma (LMS) method., Results: The paravertebral muscles exhibited an age-related decline in muscle area and density, coupled with an increase in muscle fat fraction. Between the ages of 25 and 75, the reductions in psoas and paraspinal muscle cross-sectional area at the L3 level were - 0.47%/yr and - 0.53%/yr in men, and - 0.19%/yr and - 0.23%/yr in women, respectively. Notably, accelerated muscle loss was observed during menopause and postmenopause in women (45-75 years) and intermittently during middle and old age in men (35-55 and 60-75 years). Besides, the age-related decreases in PSMA, PMA, and PSMD and the increases in PSMFF were more pronounced in L5 than in L3 CONCLUSION: This study shows distinct patterns of accelerated muscle loss were identified in menopausal and postmenopausal women and in middle-aged and old men. The findings contribute valuable information for future investigations on paravertebral muscle loss and myosteatosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Introduction: In infants with cholestasis, variations in the enterohepatic circulation of bile acids and the gut microbiota (GM) characteristics differ between those with biliary atresia (BA) and non-BA, prompting a differential analysis of their respective GM profiles., Methods: Using 16S rDNA gene sequencing to analyse the variance in GM composition among three groups: infants with BA (BA group, n=26), non-BA cholestasis (IC group, n=37), and healthy infants (control group, n=50). Additionally, correlation analysis was conducted between GM and liver function-related indicators., Results: Principal component analysis using Bray-Curtis distance measurement revealed a significant distinction between microbial samples in the IC group compared to the two other groups. IC-accumulated co-abundance groups exhibited positive correlations with aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, and total bile acid serum levels. These correlations were notably reinforced upon the exclusion of microbial samples from children with BA., Conclusion: The varying "enterohepatic circulation" status of bile acids in children with BA and non-BA cholestasis contributes to distinct GM structures and functions. This divergence underscores the potential for targeted GM interventions tailored to the specific aetiologies of cholestasis., 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 Liu, Zhang, Guo, Li, Wang and Zhang.)

Recently, research on the human microbiome, especially concerning the bacteria within the digestive system, has substantially advanced. This exploration has unveiled a complex interplay between microbiota and health, particularly in the context of disease. Evidence suggests that the gut microbiome plays vital roles in digestion, immunity and the synthesis of vitamins and neurotransmitters, highlighting its significance in maintaining overall health. Conversely, disruptions in these microbial communities, termed dysbiosis, have been linked to the pathogenesis of various diseases, including digestive system cancers. These bacteria can influence cancer progression through mechanisms such as DNA damage, modulation of the tumour microenvironment, and effects on the host's immune response. Changes in the composition and function within the tumours can also impact inflammation, immune response and cancer therapy effectiveness. These findings offer promising avenues for the clinical application of intratumoral bacteria for digestive system cancer treatment, including the potential use of microbial markers for early cancer detection, prognostication and the development of microbiome-targeted therapies to enhance treatment outcomes. This review aims to provide a comprehensive overview of the pivotal roles played by gut microbiome bacteria in the development of digestive system cancers. Additionally, we delve into the specific contributions of intratumoral bacteria to digestive system cancer development, elucidating potential mechanisms and clinical implications. Ultimately, this review underscores the intricate interplay between intratumoral bacteria and digestive system cancers, underscoring the pivotal role of microbiome research in transforming diagnostic, prognostic and therapeutic paradigms for digestive system cancers., (© 2024. The Author(s).)

The electrooxidation of 5-hydroxymethylfurfural (HMF) into 2,5-furandicarboxylic acid (FDCA) demonstrated its unique superiority, not only in reducing overpotential and improving energy conversion efficiency for green hydrogen production but also in utilizing abundant biomass resources and producing high-value-added chemicals. However, designing highly efficient electrocatalysts for HMF electrooxidation (HMF-EOR) with low cost and high performance for large-scale production remained a huge challenge. Herein, we introduced an easy one-step activation process to produce P-doped porous biochar loaded with multiple crystal surfaces exposed to CoP 2 O 6 catalysts (CoP 2 O 6 @PC), which exhibited outstanding electrooxidation performance. To achieve a current density of 50 mA cm -2 , only a low overpotential of 200 mV was needed for the electrooxidation of HMF in 1.0 M KOH + 10 mM HMF. This performance far surpassed that of other similar materials. CoP 2 O 6 @PC exhibited outstanding HMF-EOR performance with high conversion (nearly 100%), selectivity (97.1%), faradaic efficiency (95.3%), and robust stability. This work represents a promising strategy to fabricate macroscale and low-cost HMF-EOR electrocatalysts and achieve potential industrial applications of HMF-EOR.

Recent studies found the intrusion and retention of exogenous fine particles into joints, but epidemiological data for long- and intermediate-term exposure associations are scare. Here, all urban working, retired employee, and rural residents (16.78 million) in Beijing from January 1, 2011 to December 31, 2019 were included to investigate the effects of long- and intermediate-term ambient particulate exposure on development of osteoarthritis. We identified 1,742,067 participants as first-visit patients with osteoarthritis. For each interquartile range increase in annual PM 2.5 (23.32 μg/m 3 ) and PM 10 (23.92 μg/m 3 ) exposure concentration, the pooled hazard ratios were respectively 1.238 (95% CI: 1.228, 1.249) and 1.178 (95% CI: 1.168, 1.189) for first osteoarthritis outpatient visits. Moreover, age at first osteoarthritis outpatient visits significantly decreased by 4.52 (95% CI: 3.45 to 5.40) days per μg/m 3 for annual PM 2.5 exposure at below 67.85 μg/m 3 . Finally, among the six constituents analyzed, black carbon appears to be the most important component associated with the association between PM 2.5 exposure and the three osteoarthritis-related outcomes.

Culm development in grasses can be controlled by both miR156 and cytokinin. However, the crosstalk between the miR156-SPL module and the cytokinin metabolic pathway remains largely unknown. Here, we found CYTOKININ OXIDASE/DEHYDROGENASE4 (PvCKX4) plays a negative regulatory role in culm development of the bioenergy grass Panicum virgatum (switchgrass). Overexpression of PvCKX4 in switchgrass reduced the internode diameter and length without affecting tiller number. Interestingly, we also found that PvCKX4 was always upregulated in miR156 overexpressing (miR156 OE ) transgenic switchgrass lines. Additionally, upregulation of either miR156 or PvCKX4 in switchgrass reduced the content of isopentenyl adenine (iP) without affecting trans-zeatin (tZ) accumulation. It is consistent with the evidence that the recombinant PvCKX4 protein exhibited much higher catalytic activity against iP than tZ in vitro. Furthermore, our results showed that miR156-targeted SPL2 bound directly to the promoter of PvCKX4 to repress its expression. Thus, alleviating the SPL2-mediated transcriptional repression of PvCKX4 through miR156 overexpression resulted in a significant increase in cytokinin degradation and impaired culm development in switchgrass. On the contrary, suppressing PvCKX4 in miR156 OE transgenic plants restored iP content, internode diameter, and length to wild-type levels. Most strikingly, the double transgenic lines retained the same increased tiller numbers as the miR156 OE transgenic line, which yielded more biomass than the wild type. These findings indicate that the miR156-SPL module can control culm development through transcriptional repression of PvCKX4 in switchgrass, which provides a promising target for precise design of shoot architecture to yield more biomass from grasses., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

The enhanced utilization of biomass-derived chemicals for the generation of high value aromatics through an advanced catalytic strategy has captured considerable attention within the realm of eco-friendly manufacturing. This work presented four innovative three-dimensional rod-shaped mesoporous Ce-based MOF materials, which were coupled with a H-donor solvent to facilitate vanillin hydrodeoxygenation and macromolecular lignin. Under the optimized conditions (30 mg CoCe@C catalyst, 2 MPa N 2 pressure, 15 mL isopropanol, 190 °C, and 5 h), the CoCe@C catalyst achieved nearly complete conversion of vanillin and demonstrated 87.8 % selectivity in the hydrogen-donor solvent. The characterization findings suggested that the synergy between metallic Co and oxygen vacancy sites enabled the effective activation of CHO group in vanillin, leading to formation of reactive product MMP. In addition, the optimal CoCe@C catalyst could also achieve macromolecular lignin hydrodeoxygenation to obtain high yield of lignin oil products with narrower molecular weight distribution. This study presented a viable approach for the concurrent utilization of lignin derivatives in the generation of high value fuels and chemicals., 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.)

South and Southeast Asia (SSA) emitted black carbon (BC) exerts potential effects on glacier and snow melting and regional climate change in the Tibetan Plateau. In this study, online BC measurements were conducted for 1 year at a remote village located at the terminus of the Mingyong Glacier below the Meili Snow Mountains. The Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) was used to investigate the contribution and potential effect of SSA-emitted BC. In addition, variations in the light absorption characteristics of BC and brown carbon (BrC) were examined. The results indicated that the annual mean concentration of BC was 415 ± 372 ngm -3 , with the highest concentration observed in April (monthly mean: 930 ± 484 ngm -3 ). BC exhibited a similar diurnal variation throughout the year, with two peaks observed in the morning (from 8:00 to 9:00 AM) and in the afternoon (from 4:00 to 5:00 PM), with even lower values at nighttime. At a short wavelength of 370 nm, the absorption coefficient (b abs ) reached its maximum value, and the majority of b abs values were < 20 Mm -1 , indicating that the atmosphere was not overloaded with BC. At the same wavelength, BrC substantially contributed to b abs , with an annual mean of 25.2 % ± 12.8 %. SSA was the largest contributor of BC (annual mean: 51.1 %) in the study area, particularly in spring (65.6 %). However, its contributions reached 20.2 % in summer, indicating non-negligible emissions from activities in other regions. In the atmosphere, the SSA BC-induced radiative forcing (RF) over the study region was positive. While at the near surface, the RF exhibited a significant seasonal variation, with the larger RF values occurring in winter and spring. Overall, our findings highlight the importance of controlling BC emissions from SSA to protect the Tibetan Plateau against pollution-related glacier and snow cover melting., 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.)

Background: Malnutrition is related to impaired oral health and function that causes poor dietary intake, declining the general health of older adults. The role of dietary intake in the association between oral function and nutritional status of Chinese older adults (aged 75 and above) was examined in this cross-sectional study., Methods: Through the randomized cluster sampling method, 267 older adults living in rural areas of Qingdao, Shandong (aged 81.4 ± 4.3, 75-94 years) were chosen as the primary research participants. A Mini Nutritional Assessment - Short Form was used to determine nutritional status, and Food Frequency Questionnaire and 24-hour Food Intake Recall were used to assess dietary intake. The oral function was evaluated by analyzing the teeth, oral problems, bite force, tongue pressure, lip sealing pressure, chewing function questionnaire, whole saliva flow rate, 10-Item Eating Assessment Tool, and water swallow test., Results: Based on the MNA-SF score, it was divided into a well-nourished group and a malnutrition group, with the malnutrition group comprising 40.6% of participants. The participants in the malnutrition group showed a higher rate of xerostomia, lower bite force, tongue pressure, and lip sealing pressure, and higher Chewing Function Questionnaire and 10-Item Eating Assessment Tool scores. Furthermore, their plant fat, iron, cereals and potatoes, vegetables, fruits, and seafood intake were relatively low. The regression model indicated that exercise frequency, stroke, chewing and swallowing function, intake of vegetables and fruits were risk factors for nutritional status of older adults., Conclusion: Malnutrition was relatively common among the Chinese older adults aged 75 and above, and it was significantly correlated with exercise frequency, stroke, chewing and swallowing function, and intake of vegetables and fruits. Therefore, nutrition management should be carried out under the understanding and guidance of the oral function and dietary intake of the older adults., (© 2024. The Author(s).)

Studies on the relationships between metal mixtures exposure and cognitive impairment in elderly individuals are limited, particularly the mechanism with metabolite. Few studies are available on the potential sex and age specific associations between metal exposure, metabolites and cognitive impairment. We examined plasma metal and blood metabolite concentrations among 1068 urban elderly participants. Statistical analysis included a battery of variable selection approaches, logistic regression for metal/metabolite associations, and Bayesian kernel machine regression (BKMR) to identify mixed effects of metals/metabolites on cognitive impairment risk. Our results showed that As was positively associated with cognitive impairment in the female (OR 95 % CI = 2.21 (1.36, 3.57)) and 60- to 70-year-old (OR 95 % CI = 2.60 (1.54, 4.41)) groups, Cr was positively associated with cognitive impairment in the male (OR 95 % CI = 2.15 (1.27, 3.63)) and 60- to 70-year-old (OR 95 % CI = 2.10 (1.24, 3.57)) groups, and Zn was negatively associated with cognitive impairment, especially in the female (OR 95 % CI = 0.46 (0.25, 0.84)), 60- to 70-year-old (OR 95 % CI =0.24 (0.12, 0.45)) and ≥ 80-year-old (OR 95 % CI = 0.19 (0.04, 0.86)) groups. Positive associations were observed between combined metals (Cr, Cu and As) and cognitive impairment, but Zn alleviated this tendency, especially in elderly individuals aged ≥80 years. Negative associations were observed between metabolites and cognitive impairment, especially in male, female and 60-70 years old groups. The mediation effects of metabolites on the association between metal exposure and cognitive impairment were observed, and the percentages of these effects were 15.60 % (Glu-Cr), 23.00 % (C5:1-Cu) and 16.36 % (Glu-Zn). Cr, Cu, and Zn could increase cognitive impairment risk through the "Malate-Aspartate Shuttle", "Glucose-Alanine Cycle", etc., pathways. Overall, we hypothesize that metabolites have mediation effects on the relationship between multi-metal exposure and cognitive impairment and that there are sex and age differences., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival. Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment (TME). Pore-forming gasdermins (GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME, however, the expressions and relationships of GSDMs with osteosarcoma remain unclear. Herein, gasdermin E (GSDME) expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients, and low GSDME expression was observed. A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction. Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction. The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction. The pyroptosis further initiated proinflammatory cytokines release, increased immune cell infiltration, activated adaptive immune responses and create a favorable immunogenic hot TME. The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma, but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma., Competing Interests: Da-Fu Chen is an editorial board member for Bioactive Materials and was not involved in the editorial review or the decision to publish this article. All authors declare that there are no competing interests., (© 2024 The Authors.)

The lining structures of tunnels are typically constructed using sprayed or cast concrete materials, and their performance and quality during tunnel excavation and blasting are crucial for the stability and safety of tunnels. Therefore, the safe distance between the lining structure and blasting source should be determined to avoid concrete damage caused by blasting vibrations. In this study, taking the subway tunnel of Danshan Station in Qingdao as an example, the JH-2 model is introduced as the constitutive model of the tunnel blasting simulation, and the JH-2 model parameters of the local surrounding rock are obtained by experiments, and finally the numerical simulation and theoretical verification are carried out to study the safety distance of shotcrete under various safety judgment standards. The results indicate that the JH-2 model can effectively simulate the propagation of stress waves under different media conditions, and the closer the strength parameters and pressure constant of the lining structure are to those of the surrounding rock, the safer the concrete-rock bonding interface. During tunnel blasting construction using the ring blasting method, the peak particle velocity (PPV) of the lining structure increases with an increase in the arch angle. Based on the numerical simulation results, we recommend that concrete lining be constructed at a distance of at least 62 m from the blasting source to avoid damage caused by vibrations. The effect of concrete tensile failure caused by longitudinal stress is much smaller than the damage to the bonding interface caused by the PPV and can be neglected., (© 2024. The Author(s).)

Objectives: To compare the performance of areal Hounsfield units (aHUs), volumetric Hounsfield units (vHUs), and volumetric bone mineral density (vBMD) by quantitative CT (QCT) in discriminating vertebral fractures (VFs) risk., Methods: We retrospectively included CT scans of the lumbar spine 101 VFs cases (60 women, mean age: 64 ± 4 years; 41 men, mean age: 73 ± 10 years) and sex- and age-matched 101 control subjects (60 women, mean age: 64 ± 4 years; 41 men, mean age: 72 ± 7 years). In order to assess the discriminatory capability of aHU, vHU, and vBMD measurements at the L1 and L2 levels in identifying VFs, we conducted binary logistic regression and receiver operating characteristic (ROC) curve analyses in men and women. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated., Results: In both men and women with and without VFs, aHU, vHU, and vBMD were highly correlated with each other (r2 from 0.832 to 0.957, all P < .001). There was a statistically significant difference in aHU, vHU, and vBMD between subjects with and without VFs (P < .001). When age, gender, and BMI were taken into account as covariances and adjusted simultaneously, odds ratios (ORs) for aHU, vHU, and vBMD values, which represent the risk of VFs, were significant (P < .001). Compared with aHU and vHU, vBMD was more strongly associated with VF risk (vBMD: OR, 6.29; 95% CI, 3.83-10.35 vs vHU: OR, 3.64; 95% CI, 2.43-5.46 vs aHU: OR, 2.56; 95% CI, 1.79-3.67). In both men and women, further, vBMD had higher values for AUC, sensitivity, specificity, PPV, and NPV compared to vHU, with vHU in turn surpassing aHU. The area under the receiver operating characteristic curve (AUC) for discriminating VFs using the average aHU, vHU, and vBMD of 2 vertebrae was 0.72, 0.77, and 0.87 in men and 0.76, 0.79, and 0.86 in women. In both men and women, there exist statistically significant differences in the AUC when employing the 3 measurements-namely, aHU, vHU, and vBMD-to discriminate fractures (P < .05)., Conclusions: The QCT-measured vBMD is more associated with acute VFs than vHU and aHU values of the lumbar spine. Although the use of vHU and aHU values for the diagnosis of osteoporosis and discriminating fracture risk is limited to scanner- and imaging protocol-specific, they have great potential for opportunistic osteoporosis screening, particularly vHU., Advances in Knowledge: The novelty of this study presents a comparison of the VF discriminative capabilities among aHU, vHU, and vBMD. The vHU values introduced in this study demonstrate a greater capacity to discriminate fractures compared to aHU, presenting an improved clinical choice. Although its discriminatory capability is slightly lower than that of vBMD, it is more convenient to measure and does not require specialized software., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Long non-coding RNAs (lncRNAs) have gathered significant attention due to their pivotal role in plant growth, development, and biotic and abiotic stress resistance. Despite this, there is still little understanding regarding the functions of lncRNA in these domains in the tea plant ( Camellia sinensis ), mainly attributable to the insufficiencies in gene manipulation techniques for tea plants. In this study, we designed a novel strategy to identify evolutionarily conserved trans -lncRNA (ECT-lncRNA) pairs in plants. We used highly consistent base sequences in the exon-overlapping region between trans -lncRNAs and their target gene transcripts. Based on this method, we successfully screened 24 ECT-lncRNA pairs from at least two or more plant species. In tea, as observed in model plants such as Arabidopsis , alfalfa, potatoes, and rice, there exists a trans -lncRNA capable of forming an ECT-lncRNA pair with transcripts of the 12-oxophytodienoate reductase ( OPR ) family, denoted as the OPRL/OPR pair. Considering evolutionary perspectives, the OPRL gene cluster in each species likely originates from a replication event of the OPR gene cluster. Gene manipulation and gene expression analysis revealed that CsOPRL influences disease resistance by regulating CsOPR expression in tea plants. Furthermore, the knockout of StOPRL1 in Solanum tuberosum led to aberrant growth characteristics and strong resistance to fungal infection. This study provides insights into a strategy for the screening and functional verification of ECT-lncRNA pairs., Competing Interests: The authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Flavonoids constitute the main nutraceuticals in the leaves of tea plants ( Camellia sinensis ). To date, although it is known that drought stress can negatively impact the biosynthesis of flavonoids in tea leaves, the mechanism behind this phenomenon is unclear. Herein, we report a protein phosphorylation mechanism that negatively regulates the biosynthesis of flavonoids in tea leaves in drought conditions. Transcriptional analysis revealed the downregulation of gene expression of flavonoid biosynthesis and the upregulation of CsMPK4a encoding a mitogen-activated protein kinase in leaves. Luciferase complementation and yeast two-hybrid assays disclosed that CsMPK4a interacted with CsWD40. Phosphorylation assay in vitro, specific protein immunity, and analysis of protein mass spectrometry indicated that Ser-216, Thr-221, and Ser-253 of CsWD40 were potential phosphorylation sites of CsMPK4a. Besides, the protein immunity analysis uncovered an increased phosphorylation level of CsWD40 in tea leaves under drought conditions. Mutation of the three phosphorylation sites generated dephosphorylated CsWD40 3A and phosphorylated CsWD40 3D variants, which were introduced into the Arabidopsis ttg1 mutant. Metabolic analysis showed that the anthocyanin and proanthocyanidin content was lower in ttg1:CsWD40 3D transgenic plants than ttg1::CsWD40 3A transgenic and wild type plants. The transient overexpression of CsWD40 3D downregulated the anthocyanidin biosynthesis in tea leaves. The dual-fluorescein protein complementation experiment showed that CsWD40 3D did not interact with CsMYB5a and CsAN2, two key transcription factors of procyanidins and anthocyanidins biosynthesis in tea plant. These findings indicate that the phosphorylation of CsWD40 by CsMPK4a downregulates the flavonoid biosynthesis in tea plants in drought stresses., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Background: High-risk human papillomavirus (HR-HPV) infection is the primary reason for cervical cancer and precancerous lesions in females. Specific immune alterations in pregnancy led to greater HR-HPV replication and reduced clearance of HR-HPV infection. This study retrospectively obtained and analyzed data from a tertiary hospital in Beijing, China. We aimed to ascertain both the genotype distribution and prevalence of HR-HPV in pregnant females. Moreover, we sought to analyze the association of HR-HPV with maternal-fetal pregnancy outcomes., Methods: The retrospective observational cohort study was divided into two parts. Part I evaluated the genotype distribution and prevalence of HR-HPV. It encompassed 6285 pregnant women who underwent a routine pregnancy check-up, Thin Prep cytology test (TCT), and HR-HPV diagnosis during weeks 12-14 of gestation between January 1, 2013, and December 31, 2021. Part II analyzed the association between HR-HPV infection and maternal-fetal pregnancy outcome. Through a nearest-neighbor 1:1 propensity score matching (PSM), we matched HR-HPV-positive and HR-HPV-negative pregnant women using caliper width equal to 0.02. After PSM, 171 HR-HPV-positive and 171 HR-HPV-negative pregnant women were included to analyze the association between HR-HPV infection and maternal-fetal pregnancy outcome., Results: In total 737 (11.73%) pregnant women were HR-HPV positive. The five most common genotypes of HR-HPV were HPV-52 (2.90%), HPV-58 (2%), HPV-16 (1.94%), HPV-51 (1.38%), and HPV-39 (1.29%). As for age-specific HPV prevalence, a "U-shaped" pattern was observed. The first and second peaks were detected in pregnant females aged <25 years and those aged ≥35 years, respectively. Our study found no significant difference between the HR-HPV-positive and the HR-HPV-negative pregnant females in the following maternal-fetal pregnancy outcomes: spontaneous abortion (1.2% for HR-HPV positive, 0% for HR-HPV negative, p = 0.478), preterm delivery (4.7% for HR-HPV positive, 5.3% for HR-HPV negative, p = 0.804), premature rupture of membrane (28.8% for HR-HPV positive, 22.8% for HR-HPV negative, p = 0.216), preeclampsia (7.6% for HR-HPV positive, 7.6% for HR-HPV negative, p = 1), oligohydramnios (8.2% for HR-HPV positive, 7% for HR-HPV negative, p = 0.683), fetal growth restriction (1.8% for HR-HPV positive, 0.6% for HPV negative, p = 0.615), placenta previa (1.2% for HR-HPV positive, 0.6% for HR-HPV negative, p = 1), postpartum hemorrhage (8.9% for HR-HPV positive, 11.2% for HR-HPV negative, p = 0.47). There was also no significant difference in delivery mode or birth weight between the two groups., Conclusions: HPV-16, 52, and 58 were the most prevalent infection genotypes in pregnant females. The study showed no significant differences between HR-HPV-positive and HR-HPV-negative groups in the maternal-fetal pregnancy outcomes.

The molecular chaperone heat shock protein 90 (HSP90) regulates multiple crucial signalling pathways in cancer by driving the maturation of key signalling components, thereby playing a crucial role in tumorigenesis and drug resistance in cancer. Inhibition of HSP90 results in metastable conformational collapse of its client proteins and their proteasomal degradation. Considerable efforts have been devoted to the development of small-molecule inhibitors targeting HSP90, and more than 20 inhibitors have been evaluated in clinical trials for cancer therapy. However, owing to disadvantages such as organ toxicity and drug resistance, only one HSP90 inhibitor has been approved for use in clinical settings. In recent years, HSP90 inhibitors used in combination with other anti-cancer therapies have shown remarkable potential in the treatment of cancer. HSP90 inhibitors work synergistically with various anti-cancer therapies, including chemotherapy, targeted therapy, radiation therapy and immunotherapy. HSP90 inhibitors can improve the pharmacological effects of the above-mentioned therapies and reduce treatment resistance. This review provides an overview of the use of combination therapy with HSP90 inhibitors and other anti-cancer therapies in clinical and preclinical studies reported in the past decade and summarises design strategies and prospects for these combination therapies. Altogether, this review provides a theoretical basis for further research and application of these combination therapies in the treatment of cancer., (© 2024. The Pharmaceutical Society of Korea.)

Purpose: Dysregulated liquid-liquid phase separation (LLPS) instigates tumorigenesis through biomolecular condensate dysfunction. However, the association between LLPS-associated genes and glioma remains underexplored., Patients and Methods: Differentially expressed genes (DEGs) of glioma were obtained from the GSE50161 dataset, including 34 glioma and 13 normal samples. We analyzed differentially expressed LLPS-related genes in glioma from public databases. These genes informed refined molecular subtyping on the TCGA-glioma dataset. CIBERSORT assessed immune cell infiltration across three subclusters. A prognostic model was devised using univariate and lasso Cox regressions on intersecting genes. Prognostic gene expression was validated in glioma cells via RT-qPCR., Results: A total of 673 differentially expressed LLPS-associated genes were identified in glioma. Three distinct molecular subtypes (C1, C2, and C3) of glioma were obtained with a marked variance in the expression of immune checkpoint genes PD1 and PDL1. Differences in immune cell infiltration were observed across subtypes. In addition, a tri-gene prognostic signature ( TAGLN2, NTNG2 , and IGF2BP2 ) was derived with significant survival differences between high and low-risk groups. The prognostic model displayed impressive AUC values for 1, 3, and 5-year survival in both training and validation sets. Further analysis highlighted a notable correlation between the three prognostic genes and immune cells in glioma samples. Furthermore, we found the upregulation of TAGLN2 and IGF2BP2 and the downregulation of NTNG2 in glioma tumors and cells., Conclusion: This study innovatively uncovers the significant role of LLPS-related genes in glioma tumor grading and prognosis. The constructed tri-gene prognostic model holds promise for enhancing personalized prognosis assessments and optimizing immunotherapy strategies for glioma patients., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Lv et al.)

Medical imaging AI systems and big data analytics have attracted much attention from researchers of industry and academia. The application of medical imaging AI systems and big data analytics play an important role in the technology of content based remote sensing (CBRS) development. Environmental data, information, and analysis have been produced promptly using remote sensing (RS). The method for creating a useful digital map from an image data set is called image information extraction. Image information extraction depends on target recognition (shape and color). For low-level image attributes like texture, Classifier-based Retrieval(CR) techniques are ineffective since they categorize the input images and only return images from the determined classes of RS. The issues mentioned earlier cannot be handled by the existing expertise based on a keyword/metadata remote sensing data service model. To get over these restrictions, Fuzzy Class Membership-based Image Extraction (FCMIE), a technology developed for Content-Based Remote Sensing (CBRS), is suggested. The compensation fuzzy neural network (CFNN) is used to calculate the category label and fuzzy category membership of the query image. Use a basic and balanced weighted distance metric. Feature information extraction (FIE) enhances remote sensing image processing and autonomous information retrieval of visual content based on time-frequency meaning, such as color, texture and shape attributes of images. Hierarchical nested structure and cyclic similarity measure produce faster queries when searching. The experiment's findings indicate that applying the proposed model can have favorable outcomes for assessment measures, including Ratio of Coverage, average means precision, recall, and efficiency retrieval that are attained more effectively than the existing CR model. In the areas of feature tracking, climate forecasting, background noise reduction, and simulating nonlinear functional behaviors, CFNN has a wide range of RS applications. The proposed method CFNN-FCMIE achieves a minimum range of 4-5% for all three feature vectors, sample mean and comparison precision-recall ratio, which gives better results than the existing classifier-based retrieval model. This work provides an important reference for medical imaging artificial intelligence system and big data analysis., (© 2024. The Author(s).)

Direct methanol fuel cells (DMFCs) are thought of as portable, sustainable, and non-polluting energy devices. The exploration of efficient and affordable catalysts for the methanol oxidation reaction (MOR) is significant for the industrial application of DMFCs. In this study, nitrogen-doped hollow carbon spheres (HCS) derived from polydopamine were proposed for the catalyst support for platinum nanoparticles (Pt NPs) for serving as the anode catalyst for DMFCs, and a composite support material was fabricated by in-situ oxidation of 3,4-ethylenedioxythiophene (ProDOT) with HCS to get core-shell structured poly(3,4-propylenedioxythiophene) (PProDOT)-embellished hollow carbon spheres (HCS) (PProDOT/HCS) for further improving the catalytic activity for supported catalyst. The results indicated that the platinum (Pt) on the surface of HCS was well dispersed, and the Pt became smaller and more evenly distributed with the introduction of PProDOT. Simultaneously, the Schottky junction formed between PProDOT and Pt NPs contributes to enhanced charge transfer and catalytic activity of the catalyst. Notably, the core-shell structure of the ternary catalyst, its excellent charge transfer capability, and the interaction between platinum and the support contribute to its high electrocatalytic activity. Electrochemical tests demonstrated that the PProDOT/HCS/Pt catalyst exhibited a mass activity of 1169.6 mA mg -1 Pt for methanol oxidation in acidic electrolytes, surpassing the activity of the HCS/Pt catalyst (472.4 mA mg -1 Pt ) and commercial Pt/C (281.0 mA mg -1 Pt )., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The MYB4 transcription factor family regulates plant traits. However, their overexpression often results in undesirable side effects like growth reduction. We have reported a green tea ( Camellia sinensis ) MYB4 transcription factor (CsMYB4) that represses the phenylpropanoid and shikimate pathways and stunts plant growth and development. In the current study, we observed that in CsMYB4a transgenic tobacco ( Nicotiana tabacum ) plants, primary metabolism was altered, including sugar and amino acid metabolism, which demonstrated a pleiotropic regulation by CsMYB4a. The CsMYB4a transgenic tobacco plants had improved drought tolerance, which correlated to alterations in carbohydrate metabolism and an increase in proline content, as revealed by metabolic profiling and transcriptomic analysis. To mitigate the undesirable repressive side effects on plant traits, including dwarfism, shrunken leaves, and shorter roots of CsMYB4a transgenic plants, we deleted the C4 domain of CsMYB4a to obtain a CsMYB4a-DC4 variant and then overexpressed it in transgenic plants (CsMYB4a-DC4). These CsMYB4a-DC4 plants displayed a normal growth and had improved drought tolerance. Metabolite analysis demonstrated that the contents of carbohydrates and proline were increased in these transgenic plants. Our findings suggest that  an approriate modification of TFs can generate novel crop traits, thus providing potential agricultural benefits and expanding its application to various crops., Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00149-5., Competing Interests: Conflict of interestsThe authors declare that they have no conflict of interest in the current research., (© The Author(s) 2024, corrected publication 2024.)