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Gastrochilus is an orchid genus containing 73 species of mainly epiphytic on trees or rocks in mountain forests of tropical and subtropical Asia. Previous phylogenetic analyses and morphological assessments have failed to produce a well-resolved phylogeny at the infrageneric level. In the present study, a new infrageneric classification of Gastrochilus is proposed based on thoroughly morphological and phylogenetic analyses based on 52 species. Our phylogenetic analysis divided the genus into six sections including three new sections, G. sect. Pseudodistichi, G. sect. Brachycaules and G. sect. Acinacifolii. We also reinstate G. suavis to the specific rank. Furthermore, two new species, G. armeniacus Jun Y. Zhang, B. Xu & Yue H. Cheng and G. minjiangensis Jun Y. Zhang, B. Xu & Yue H. Cheng, are described and illustrated. A key to six sections of the genus is presented.

Lung cancer has surpassed other types of cancer to become the primary cause of cancer-related deaths. Surgery stands as the foremost clinical treatment strategy available for tackling this condition, but it receives a low efficiency for most patients. In recent years, some adjuvant therapies are employed to improve the lung cancer treatment efficiency, such as chemotherapy, targeted therapy and immunotherapy. However, these strategies have not significantly increased overall survival of patients. Additionally, the random distribution of drugs will induce severe side effects. Nanomedicines have got great attentions to boost drug effect and reduce adverse reactions, including liposome-based nanoparticles, polymeric nanoparticles, inorganic nanoparticles, and exosomes. Importantly, nanomedicines contribute to improving drug bioavailability, stability and residency in target regions. Benefiting from the physiological characteristics of lung, the inhaled pulmonary delivery strategy in combination with nanomedicine will provide a non-invasive and effective strategy for treating lung cancer. Furthermore, the use of targeting ligands enables precise delivery of loaded drugs to lung cancer cells. Inhaled nanomedicine exhibits unique distribution and sustained release behaviors in the alveoli, amplifying the therapeutic effect and reducing side effects. This review aims to discuss various inhaled methods of delivering nanomedicine to treat lung cancer and also summarizes the clearance mechanism of nanomedicine in the lung. Overall, this review focuses on the application of different inhalable nanomedicines, which may inspire the development of more effective treatments against lung cancer.

Background Various limitations have impacted research evaluating reader agreement for Liver Imaging Reporting and Data System (LI-RADS). Purpose To assess reader agreement of LI-RADS in an international multicenter multireader setting using scrollable images. Materials and Methods This retrospective study used deidentified clinical multiphase CT and MRI and reports with at least one untreated observation from six institutions and three countries; only qualifying examinations were submitted. Examination dates were October 2017 to August 2018 at the coordinating center. One untreated observation per examination was randomly selected using observation identifiers, and its clinically assigned features were extracted from the report. The corresponding LI-RADS version 2018 category was computed as a rescored clinical read. Each examination was randomly assigned to two of 43 research readers who independently scored the observation. Agreement for an ordinal modified four-category LI-RADS scale (LR-1, definitely benign; LR-2, probably benign; LR-3, intermediate probability of malignancy; LR-4, probably hepatocellular carcinoma [HCC]; LR-5, definitely HCC; LR-M, probably malignant but not HCC specific; and LR-TIV, tumor in vein) was computed using intraclass correlation coefficients (ICCs). Agreement was also computed for dichotomized malignancy (LR-4, LR-5, LR-M, and LR-TIV), LR-5, and LR-M. Agreement was compared between research-versus-research reads and research-versus-clinical reads. Results The study population consisted of 484 patients (mean age, 62 years ± 10 [SD]; 156 women; 93 CT examinations, 391 MRI examinations). ICCs for ordinal LI-RADS, dichotomized malignancy, LR-5, and LR-M were 0.68 (95% CI: 0.61, 0.73), 0.63 (95% CI: 0.55, 0.70), 0.58 (95% CI: 0.50, 0.66), and 0.46 (95% CI: 0.31, 0.61) respectively. Research-versus-research reader agreement was higher than research-versus-clinical agreement for modified four-category LI-RADS (ICC, 0.68 vs 0.62, respectively; P = .03) and for dichotomized malignancy (ICC, 0.63 vs 0.53, respectively; P = .005), but not for LR-5 (P = .14) or LR-M (P = .94). Conclusion There was moderate agreement for LI-RADS version 2018 overall. For some comparisons, research-versus-research reader agreement was higher than research-versus-clinical reader agreement, indicating differences between the clinical and research environments that warrant further study. © RSNA, 2023 Supplemental material is available for this article. See also the editorials by Johnson and Galgano and Smith in this issue.

The potential for reducing greenhouse gas (GHG) emissions and energy consumption in wastewater treatment can be realized through intelligent control, with machine learning (ML) and multimodality emerging as a promising solution. Here, we introduce an ML technique based on multimodal strategies, focusing specifically on intelligent aeration control in wastewater treatment plants (WWTPs). The generalization of the multimodal strategy is demonstrated on eight ML models. The results demonstrate that this multimodal strategy significantly enhances model indicators for ML in environmental science and the efficiency of aeration control, exhibiting exceptional performance and interpretability. Integrating random forest with visual models achieves the highest accuracy in forecasting aeration quantity in multimodal models, with a mean absolute percentage error of 4.4% and a coefficient of determination of 0.948. Practical testing in a full-scale plant reveals that the multimodal model can reduce operation costs by 19.8% compared to traditional fuzzy control methods. The potential application of these strategies in critical water science domains is discussed. To foster accessibility and promote widespread adoption, the multimodal ML models are freely available on GitHub, thereby eliminating technical barriers and encouraging the application of artificial intelligence in urban wastewater treatment.

Abstract Background Myocardial infarction (MI) poses a global public health challenge, often associated with elevated mortality rates and a grim prognosis. A crucial aspect of the inflammatory injury and healing process post-MI involves the dynamic differentiation of macrophages. A promising strategy to alleviate myocardial damage after MI is by modulating the inflammatory response and orchestrating the shift from pro-inflammatory (M1) to anti-inflammatory (M2) macrophages, aiming to achieve a reduced M1/M2 ratio. Nuanxinkang (NXK), a simplified herbal decoction, has demonstrated noteworthy cardioprotective, inflammation-regulating, and myocardial energy metabolism-regulating properties. Methods In this study, we constructed an MI model by ligating coronary arteries to investigate the efficacy of NXK in improving ventricular remodeling and cardiac function. Mice were administered NXK (1.65 g/kg/d) or an equivalent volume of regular saline via gavage for 28 consecutive days, commencing the day after surgery. Then, we conducted echocardiography to assess the cardiac function, Masson staining to illustrate the extent of myocardial fibrosis, TUNEL staining to reveal myocardial apoptosis, and flow cytometry to analyze the polarization of M1 and M2 macrophages in the hearts. Besides, a lipopolysaccharide (LPS)-induced pro-inflammatory macrophage (M1) polarization model was implemented in RAW264.7 cells to elucidate the underlying mechanism of NXK in regulating macrophage polarization. RAW264.7 cells were pre-treated with or without NXK-containing serum. Oxidative stress was detected by MitoSox staining, followed by Seahorse energy metabolism assay to evaluate alterations in mitochondrial metabolic patterns and ATP production. Both In vivo and in vitro, HIF-1α and PDK1 were detected by fluorescent quantitative PCR and Western blotting. Results In vivo, MI mice exhibited a decline in cardiac function, adverse ventricular remodeling, and an increase in glycolysis, coupled with M1-dominant polarization mediated by the HIF-1α/PDK1 axis. Notably, robust responses were evident with high-dose NXK treatment (1.65 g/kg/day), leading to a significant enhancement in cardiac function, inhibition of cardiac remodeling, and partial suppression of macrophage glycolysis and the inflammatory phenotype in MI mice. This effect was achieved through the modulation of the HIF-1α/PDK1 axis. In vitro, elevated levels of mitochondrial ROS production and glycolysis were observed in LPS-induced macrophages. Conversely, treatment with NXK notably reduced the oxidative stress damage induced by LPS and enhanced oxidative phosphorylation (OXPHOS). Furthermore, NXK demonstrated the ability to modify the energy metabolism and inflammatory characteristics of macrophages by modulating the HIF-1α/PDK1 axis. The influence of NXK on this axis was partially counteracted by the HIF-1α agonist DMOG. And NXK downregulated PDK1 expression, curtailed glycolysis, and reversed LPS-induced M1 polarization in macrophages, similar to the PDK1 inhibitor DCA. Conclusion In conclusion, NXK protects against MI-induced cardiac remodeling by inducing metabolic reprogramming and phenotypic differentiation of macrophages, achieved through the modulation of the HIF-1α/PDK1 axis. This provides a novel and promising strategy for the treatment of MI.

Background: As an innovative treatment, stapled transperineal rectovaginal fistula repair (STR) for rectovaginal fistula (RVF) has demonstrated effectiveness in preliminary reports. This study aims to compare STR with rectal mucosal advancement flap repair (RAF), a widely utilized surgical procedure, for the surgical outcome of the low- and mid-level RVF. Methods: In this retrospective cohort study, patients with low- and mid-level RVF who underwent STR or RAF were included from both the Sixth Affiliated Hospital of Sun Yat-sen University and Xi'an Daxing Hospital. Among the 99 total patients, 77 underwent STR and 22 underwent RAF. Patient demographics, operative data, and outcomes were collected and analyzed. Recurrence rate and associated risk factors were evaluated. Results: There were no statistically significant differences among patients in terms of clinical characteristics like age, BMI, aetiology, and fistula features. During the follow-up period of 20 months (interquartile range 3.0–41.8 months), a total of 28 patients relapsed, with a significantly lower recurrence rate in the STR group (20.8 %) than in the RAF group (54.6 %) (P = 0.005). In the multivariate Cox analysis, STR was an independent protective factor against recurrence (HR: 0.37, 95%CI: 0.17–0.79, P = 0.01). Logistic regression indicated that there was no statistically significant difference between these two procedures in terms of surgical complications (OR: 0.53, 95%CI: 0.19–1.48, P = 0.23). Conclusion: For low- and mid-level RVF, STR may be an alternative option for treatment modality that offers a lower recurrence rate, without observed disadvantage in terms of surgical complication rates.

High entropy alloys （HEAs） have excellent properties because they can form simple solid solution (SS) phases, including body-centered cubic (BCC) phase, face-centered cubic (FCC) phase, or FCC + BCC phase, so phase prediction is the first step in alloy design. In current research, machine learning (ML) approach had been widely used to guide the discovery and design of materials. The prediction of HEAs phase structure based on machine learning (ML) is a hot topic. In this work, five ML algorithms were utilized to predict HEAs for SS and amorphous (AM) phases based on 399 collected data sets, including 120 BCC alloys, 87 FCC alloys, 82 BCC + FCC alloys and 110 a.m. alloys. To enhance the model's accuracy, grid search and K-fold cross validation were used to optimize performance. Valence electron concentration (VEC) and ΔHmix exhibit high importance in prediction in compared to other parameters. The results show that the random forest can effectively distinguish BCC phase, FCC phase, mixed solid solution phase (FCC + BCC) and AM, with an accuracy is 0.87. After that, the CoCrFeNiAlx (x = 0, 0.5, 1) system alloys were characterized by XRD and SEM-EDS. The experimental results validated that the phase structure of CoCrFeNiAlx alloys changed from FCC to BCC + FCC and BCC with the increase of Al content, which is consistent with the ML prediction.

Abstract Background Sarcopenia is highly prevalent among patients with colorectal cancer (CRC). Computed tomography (CT)‐based assessment of low skeletal muscle index (SMI) is widely used for diagnosing sarcopenia. However, there are conflicting findings on the association between low SMI and overall survival (OS) in CRC patients. The objective of this study was to investigate whether CT‐determined low SMI can serve as a valuable prognostic factor in CRC. Methods We collected data from patients with CRC who underwent radical surgery at our institution between June 2020 and November 2021. The SMI at the third lumbar vertebra was calculated using CT scans, and the cutoff values for defining low SMI were determined using receiver operating characteristic curves. Univariate and multivariate analyses were performed to assess the associations between clinical characteristics and postoperative major complications. Results A total of 464 patients were included in the study, 229 patients (46.7%) were classified as having low SMI. Patients with low SMI were older and had a lower body mass index (BMI), a higher neutrophil to lymphocyte ratio (NLR), and higher nutritional risk screening 2002 (NRS2002) scores compared to those with normal SMI. Furthermore, patients with sarcopenia had a higher rate of major complications (10.9% vs. 1.3%; p

To verify the predictive accuracy of existing strength criteria on true triaxial strength experimental data, understand the characteristics of different strength criteria, and provide a basis for selecting strength criteria for engineering applications, ten commonly used rock strength criteria were selected and divided into MC and HB types. The distribution characteristics of the yield surfaces and yield curves of different criteria were compared and analyzed in the principal stress space and the π plane. Afterwards, based on the least absolutely deviation method, these ten strength criteria were used to predict 32 sets of true triaxial rock strength experimental data. The results showed that the range of undetermined parameters for MC type strength criteria was small and easy to determine, while the range of undetermined parameter for HB type criteria was large and difficult to determine the search range, in addition, the fitting process may not converge. The fitting accuracy of strength criteria for true triaxial experimental data depends on the sensitivity of rock strength to the intermediate principal stress. PH and GP criteria are the most sensitive to changes of the intermediate principal stress, followed by MWC and ML criteria, MGC and ZZ criteria, MCJP and HBWW criteria. PH and GP criteria overestimate the effect of the intermediate principal stress, resulting in the largest prediction errors, while the other three-dimensional strength criteria have high prediction accuracy and no significant differences. The research results can provide scientific basis for engineering design, geological hazard prediction, and mineral resource development.

Evidence has demonstrated that exoskeleton robots can improve intestinal function in patients with spinal cord injury (SCI). However, the underlying mechanisms remain unelucidated. This study investigated the effects of exoskeleton-assisted walking (EAW) on intestinal function and intestinal flora structure in T2-L1 motor complete paraplegia patients. The results showed that five participants in the EAW group and three in the conventional group reported improvements in at least one bowel management index, including an increased frequency of bowel evacuations, less time spent on bowel management per day, and less external assistance (manual digital stimulation, medication, and enema usage). After 8 weeks of training, the amount of glycerol used in the EAW group decreased significantly (p

IntroductionSimultaneous chemical phosphorus removal process using iron salts (Fe(III)) has been widely utilized in wastewater treatment to meet increasingly stringent discharge standards. However, the inhibitory effect of Fe(III) on the biological phosphorus removal system remains a topic of debate, with its precise mechanism yet to be fully understood.MethodsBatch and long-term exposure experiments were conducted in six sequencing batch reactors (SBRs) operating for 155 days. Synthetic wastewater containing various Fe/P ratios (i.e., Fe/P = 1, 1.2, 1.5, 1.8, and 2) was slowly poured into the SBRs during the experimental period to assess the effects of acute and chronic Fe(III) exposure on polyphosphate-accumulating organism (PAO) growth and phosphorus metabolism.ResultsExperimental results revealed that prolonged Fe(III) exposure induced a transition in the dominant phosphorus removal mechanism within activated sludge, resulting in a diminished availability of phosphorus for bio-metabolism. In Fe(III)-treated groups, intracellular phosphorus storage ranged from 3.11 to 7.67 mg/g VSS, representing only 26.01 to 64.13% of the control. Although the abundance of widely reported PAOs (Candidatus Accumulibacter) was 30.15% in the experimental group, phosphorus release and uptake were strongly inhibited by high dosage of Fe(III). Furthermore, the abundance of functional genes associated with key enzymes in the glycogen metabolism pathway increased while those related to the polyphosphate metabolism pathway decreased under chronic Fe(III) stress.DiscussionThese findings collectively suggest that the energy generated from polyhydroxyalkanoates oxidation in PAOs primarily facilitated glycogen metabolism rather than promoting phosphorus uptake. Consequently, the dominant metabolic pathway of communities shifted from polyphosphate-accumulating metabolism to glycogen-accumulating metabolism as the major contributor to the decreased biological phosphorus removal performance.

Physical therapists play a crucial role in guiding patients through effective and safe rehabilitation processes according to medical guidelines. However, due to the therapist-patient imbalance, it is neither economical nor feasible for therapists to provide guidance to every patient during recovery sessions. Automated assessment of physical rehabilitation can help with this problem, but accurately quantifying patients’ training movements and providing meaningful feedback poses a challenge. In this paper, an Expert-knowledge-based Graph Convolutional approach is proposed to automate the assessment of the quality of physical rehabilitation exercises. This approach utilizes experts’ knowledge to improve the spatial feature extraction ability of the Graph Convolutional module and a Gated pooling module for feature aggregation. Additionally, a Transformer module is employed to capture long-range temporal dependencies in the movements. The attention scores and weight matrix obtained through this approach can serve as interpretability tools to help therapists understand the assessment model and assist patients in improving their exercises. The effectiveness of the proposed method is verified on the KIMORE dataset, achieving state-of-the-art performance compared to existing models. Experimental results also illustrate the interpretability of the method in both spatial and temporal dimensions.

Abstract Objective Antimicrobial resistance (AMR) has emerged as a serious global public health crisis. In response, 2016, 14 ministries in China, under the leadership of the National Health Commission, collaboratively issued the National Action Plan (NAP) to Contain Antibacterial Resistance (2016–2020). The NAP outlines strategies for medical institutions to adopt stewardship and implement AMR control. The purpose of this study was to comprehend stakeholders’ perceptions of the NAP and explore the factors that influence its implementation in medical institutions. Methods Semi-structured interviews were conducted with practitioners from medical institution in March and April 2021. Interviews were audio-recorded, transcribed and analyzed using thematic analysis via the framework approach. Results Twenty practitioners, representing diverse roles (4 administrators, 7 clinicians, 3 microbiologists, 3 pharmacists, 3 nosocomial infection management personnel) from seven institutions, participated in the study. Substantial efforts have been undertaken to regulate the rational use of antibiotics and enhance the management of hospital infections. Participants demonstrated awareness and concern regarding antimicrobial resistance, with widespread support expressed for the NAP. Among all professions, there were varying opinions on whether they felt restricted in their daily work. The tertiary hospitals have established multidisciplinary cooperation mechanisms. Six main themes were identified as both barriers and facilitators to the implementation of the NAP in the medical institutions: individual factors, leadership, multidisciplinary collaboration, patient factors, training and culture. The capacity for administrative attention is constrained or limited, poor enforcement of guidelines, insufficient specialist staff and the liability pressure on clinicians were perceived barriers. To containing AMR in medical institutions, management of hospital infections, the public’s knowledge of antibiotics’ usage, routine education and multidisciplinary support would be facilitators. Conclusions Practitioners from medical institutions were highly supportive for the NAP. Consideration of practitioners’ perceived barriers and facilitators might enhance implementation of the NAP to contain antimicrobial resistance.

Abstract Background Although some studies suggest that robot-assisted technology can significantly improve upper limb function in stroke patients compared to traditional rehabilitation training, it is still necessary to incorporate an auxiliary intervention to alleviate negative emotions, thereby alleviating the post-stroke fatigue and encouraging patients to actively respond to rehabilitation. However, the effect of the auxiliary intervention is unknown. Objective To evaluate the effect of reminiscent music therapy combined with robot-assisted rehabilitation in elderly patients with upper limb dysfunction. Methods From November 2022 to March 2023, elderly patients with upper limb dysfunction after stroke were assigned to one of three groups, with group A receiving usual rehabilitation treatment and care plus robot-assisted rehabilitation and reminiscent music therapy, group B receiving usual rehabilitation treatment and care plus robot-assisted rehabilitation, and group C receiving only usual rehabilitation treatment and care. Thirty patients completed this study, with 10 participants in each group. Activities of daily living, self-esteem, rehabilitation self-efficacy, positive emotion and upper limb function were measured before and after the intervention. One-way analysis of variance, paired-sample t-test, Kruskal-Wallis H test, Wilcoxon signed rank sum test and Chi-square test were used to analyze the data. Results According to the intragroup comparisons, in the three groups, all outcome measurements were significantly higher than those at baseline (all P

Uremic toxins play a crucial role in the development of low bone turnover disease in chronic kidney disease (CKD) through the induction of oxidative stress. This oxidative stress disrupts the delicate balance between bone formation and resorption, resulting in a decline in both bone quantity and quality. Reactive oxygen species (ROS) activate nuclear factor kappa-B and mitogen-activated protein kinase signaling pathways, promoting osteoclastogenesis. Conversely, ROS hinder osteoblast differentiation by facilitating the binding of Forkhead box O proteins (FoxOs) to β-catenin, triggering apoptosis through FoxOs-activating kinase phosphorylation. This results in increased osteoblastic receptor activator of nuclear factor kappa-B ligand (RANKL) expression and decreased nuclear factor erythroid 2-related factor 2 levels, compromising antioxidant defenses against oxidative damage. As CKD progresses, the accumulation of protein-bound uremic toxins such as indoxyl sulfate (IS) and p-cresyl sulfate (PCS) intensifies oxidative stress, primarily affecting osteoblasts. IS and PCS directly inhibit osteoblast viability, induce apoptosis, decrease alkaline phosphatase activity, and impair collagen 1 and osteonectin, impeding bone formation. They also reduce cyclic adenosine 3',5'-monophosphate (cAMP) production and lower parathyroid hormone (PTH) receptor expression in osteoblasts, resulting in PTH hyporesponsiveness. In summary, excessive production of ROS by uremic toxins not only reduces the number and function of osteoblasts but also induces PTH hyporesponsiveness, contributing to the initiation and progression of low bone turnover disease in CKD.

Abstract Background Breast cancer is the second leading cause of cancer-related death in women, and drug resistance during treatment is a major challenge. However, the mechanisms underlying drug resistance are not fully understood. Here we applied whole-exome sequencing (WES) to clarify resistant rules to Herceptin and tyrosine kinase inhibitors (TKIs). Methods There are 12 HER2+ breast cancer patients who were done WES. Samples from tumor and surrounding tissues underwent DNA sequencing and analysis. Various experimental and bioinformatics techniques were employed, including genomic capture, mutation analysis (Genome Analysis Toolkit (GATK), etc.), bioinformatics assessments, and drug-gene interaction investigations. Ultimately, the study explored the association of APOB gene expression with breast cancer recurrence rates, immune cell infiltration, and drug response. Results The C > T mutation frequency was highest in the Herceptin-insensitive (HI) and verification groups, codenamed YI, contrasting with the Herceptin-sensitive (HE) group. No microsatellite instability (MSI)-H patients were in the HE group, but both HI and YI groups had 1 each. Significant differences in transition-transversion (TiTv) were observed in the HI and YI groups rather than the HE group. In the TKI- insensitive (TI) group, C > T mutations were highest, differing from the TKI-sensitive (TE) group. TE group included 2 MSI-H patients. Significant differences in TiTv were found in the TI group rather than the TE group. Mutated APOB may resist Herceptin and TKI, increasing immune infiltration. We identified potential drugs targeting it. Conclusions Our study suggested that a higher percentage of C > T mutations, significant differences in TiTv, and MSI-H status may indicate Herceptin resistance, while a higher percentage of C > T mutations, significant differences in TiTv, and the absence of MSI-H may indicate TKI resistance in breast cancer patients. For patients resistant to both Herceptin and TKI, mutated APOB may play a crucial role in resistance.

Abstract Background It remains controversial whether the long-term use of statins or newer nonstatin drugs has a positive effect on human longevity. Therefore, this study aimed to investigate the genetic associations between different lipid-lowering therapeutic gene targets and human longevity. Methods Two-sample Mendelian randomization analyses were conducted. The exposures comprised genetic variants that proxy nine drug target genes mimicking lipid-lowering effects (LDLR, HMGCR, PCKS9, NPC1L1, APOB, CETP, LPL, APOC3, and ANGPTL3). Two large-scale genome-wide association study (GWAS) summary datasets of human lifespan, including up to 500,193 European individuals, were used as outcomes. The inverse-variance weighting method was applied as the main approach. Sensitivity tests were conducted to evaluate the robustness, heterogeneity, and pleiotropy of the results. Causal effects were further validated using expression quantitative trait locus (eQTL) data. Results Genetically proxied LDLR variants, which mimic the effects of lowering low-density lipoprotein cholesterol (LDL-C), were associated with extended lifespan. This association was replicated in the validation set and was further confirmed in the eQTL summary data of blood and liver tissues. Mediation analysis revealed that the genetic mimicry of LDLR enhancement extended lifespan by reducing the risk of major coronary heart disease, accounting for 22.8% of the mediation effect. The genetically proxied CETP and APOC3 inhibitions also showed causal effects on increased life expectancy in both outcome datasets. The lipid-lowering variants of HMGCR, PCKS9, LPL, and APOB were associated with longer lifespans but did not causally increase extreme longevity. No statistical evidence was detected to support an association between NPC1L1 and lifespan. Conclusion This study suggests that LDLR is a promising genetic target for human longevity. Lipid-related gene targets, such as PCSK9, CETP, and APOC3, might potentially regulate human lifespan, thus offering promising prospects for developing newer nonstatin therapies.

Abstract Introduction Inflammation and nerve injury promote astrocyte activation, which regulates the development and resolution of pain, in the spinal dorsal horn. APOE regulates lipid metabolism and is predominantly expressed in the astrocytes. However, the effect of astrocytic APOE and lipid metabolism on spinal cellular function is unclear. This study aimed to investigate the effect of spinal Apoe on spinal cellular functions using the complete Freund's adjuvant (CFA)-induced inflammatory pain mouse model. Methods After intraplantar injection of CFA, we assessed pain behaviors in C57BL6 and Apoe knockout (Apoe −/− ) mice using von Frey and Hargreaves’ tests and analyzed dorsal horn samples (L4-5) using western blotting, immunofluorescence, quantitative real-time polymerase chain reaction, and RNA sequencing. Results The Apoe levels were markedly upregulated at 2 h and on days 1 and 3 post-CFA treatment. Apoe was exclusively expressed in the astrocytes. Apoe −/− mice exhibited decreased pain on day 1, but not at 2 h, post-CFA treatment. Apoe −/− mice also showed decreased spinal neuron excitability and paw edema on day 1 post-CFA treatment. Global transcriptomic analysis of the dorsal horn on day 1 post-CFA treatment revealed that the differentially expressed mRNAs in Apoe −/− mice were associated with lipid metabolism and the immune system. Astrocyte activation was impaired in Apoe −/− mice on day 1 post-CFA treatment. The intrathecal injection of Apoe antisense oligonucleotide mitigated CFA-induced pain hypersensitivity. Conclusions Apoe deficiency altered lipid metabolism in astrocytes, exerting regulatory effects on immune response, astrocyte activation, and neuronal activity and consequently disrupting the maintenance of inflammatory pain after peripheral inflammation. Targeting APOE is a potential anti-nociception and anti-inflammatory strategy.

Early diagnosis of non-Hodgkin lymphoma (NHL) is crucial for effective management. We report an ultrasensitive electrochemical genosensor using multi-walled carbon nanotube (MWCNT)-graphene nanocomposite for detection of lymphoma biomarker gene. MWCNTs were dispersed over graphene nanoplatelets to form a conductive nanocomposite platform. The high surface area and π-π stacking ability enabled efficient immobilization of lymphoma probe DNA. Detailed materials characterization was performed using microscopy and spectroscopy techniques. The sensor was fabricated by drop-casting probe-conjugated nanocomposite suspension onto a glassy carbon electrode. The genosensor exhibited a wide dynamic range of 1 fM to 1 nM with a sensitivity of 0.895 kΩ per decade of target concentration. The sensor showed excellent selectivity for fully complementary target sequence over even single base mismatch. Hybridization detection by electrochemical impedance spectroscopy was further validated using differential pulse voltammetry which showed drastic reduction in redox peak current after incubating with target. The nanocomposite genosensor demonstrated good reproducibility with relative standard deviation of 3.72 % among five independently prepared electrodes. Clinical applicability was tested by spiking lymphoma gene biomarker in 10 % serum and recoveries of 93–99 % were obtained. The proposed MWCNT-graphene nanocomposite genosensor provides a simple, specific and ultrasensitive platform for point-of-care diagnosis of NHL.

Although significant differences in soil nitrogen levels exist under different paddy-upland rotations, the main reason for this is unclear. The nitrogen retention capacity and loss of ammonia volatilisation, leaching, etc. of paddy soil with large differences in nitrogen levels from two long-term rotations, garlic-rice and wheat-rice, were measured using the soil column simulation method. The results showed that the loss rate of leaching was only 5.4%, whereas that of ammonia volatilisation was up to 22.8%, which was the main nitrogen loss way of paddy soil under the two rotations. The average ammonia volatilisation rates under wheat-rice rotation with high and low nitrogen application rates were 12.1% and 40.2% higher than that under garlic-rice rotation, leading to a decrease in the total nitrogen loss amount and rate through ammonia volatilisation by 29.8% and 8.8%, respectively. As a result, nitrogen retention in the soil under garlic-rice rotation increased by 12.7%. In conclusion, the long-term garlic-rice rotation could significantly inhibit ammonia volatilisation, thus improving the soil nitrogen retention capacity. The straw return may increase soil organic matter content, reduce ammonia volatilisation loss, and enhance soil nitrogen retention capacity and productivity.

Ageing is an inevitable process that affects various tissues and organs of the human body, leading to a series of physiological and pathological changes. Mechanisms such as telomere depletion, stem cell depletion, macrophage dysfunction, and cellular senescence gradually manifest in the body, significantly increasing the incidence of diseases in elderly individuals. These mechanisms interact with each other, profoundly impacting the quality of life of older adults. As the ageing population continues to grow, the burden on the public health system is expected to intensify. Globally, the prevalence of musculoskeletal system diseases in elderly individuals is increasing, resulting in reduced limb mobility and prolonged suffering. This review aims to elucidate the mechanisms of ageing and their interplay while exploring their impact on diseases such as osteoarthritis, osteoporosis, and sarcopenia. By delving into the mechanisms of ageing, further research can be conducted to prevent and mitigate its effects, with the ultimate goal of alleviating the suffering of elderly patients in the future.

Objective To investigate the differences in myopia prevalence and ocular biometry in children and adolescents in Chongqing and Tibet, China.Design Cross-sectional study.Setting The study included children and adolescents aged 6–18 years in Chongqing, a low-altitude region, and in Qamdo, a high-altitude region of Tibet.Participants A total of 448 participants in Qamdo, Tibet, and 748 participants in Chongqing were enrolled in this study.Methods All participants underwent uncorrected visual acuity assessment, non-cycloplegic refraction, axial length (AL) measurement, intraocular pressure (IOP) measurement and corneal tomography. And the participants were grouped according to age (6–8, 9–11, 12–14 and 15–18 years group), and altitude of location (primary school students: group A (average altitude: 325 m), group B (average altitude: 2300 m), group C (average altitude: 3250 and 3170 m) and group D (average altitude: 3870 m)).Results There was no statistical difference in mean age (12.09±3.15 vs 12.2±3.10, p=0.549) and sex distribution (males, 50.4% vs 47.6%, p=0.339) between the two groups. The Tibet group presented greater spherical equivalent (SE, −0.63 (−2.00, 0.13) vs −0.88 (−2.88, –0.13), p

Membranous nephropathy (MN) is a glomerular disease mediated by autoimmune complex deposition, with approximately 30% of cases attributed to secondary causes. Among them, malignant tumors are a significant cause of secondary MN. Recent advancements in the identification of MN-specific antigens, such as THSD7A and NELL-1, suggest a potential association with malignant tumors, yet definitive proof of this relationship remains elusive. Therefore, this article aims to review the distribution of MN-specific antigens in patients with MN caused by malignant tumors and the possible role of these antigens in the pathogenesis of the disease.

BackgroundStroke is the main disease that causes the burden of neurological disease, leading to upper limb dysfunction and affecting their self-care abilities. Robot-assisted rehabilitation therapy has been gradually used in the rehabilitation of upper limb function after stroke. However, it would be beneficial to explore auxiliary interventions such as reminiscent music therapy, a combination of music and reminiscent, to relieve negative emotions and post-stroke fatigue and improve rehabilitation outcomes. This protocol aims to evaluate the effectiveness of reminiscent music therapy combined with robot-assisted rehabilitation in older stroke patients.MethodsThis trial is a single-blind, three-arm randomized controlled trial. Older stroke patients with upper limb dysfunction will be recruited. Participants will be randomly assigned to receive usual rehabilitation treatment and care, usual rehabilitation treatment and care plus robot-assisted rehabilitation and reminiscent music therapy, or usual rehabilitation treatment and care plus robot-assisted rehabilitation. Robot-assisted rehabilitation will be conducted by rehabilitation doctors five times per week for 3 weeks. In experimental group 1, a reminiscent song list will be played for patients. The primary outcome is activities of daily living. All outcomes will be evaluated at baseline and in the week immediately post-intervention.DiscussionWe are conducting the first randomized controlled trial on the effects of reminiscent music therapy combined with robot-assisted rehabilitation in older stroke patients. It is expected that this study, if proven effective in improving the activities of daily living in older stroke patients with upper limb dysfunction, will provide evidence-based rehabilitation strategies for medical staff.Clinical Trial Registration: ChiCTR2200063738.

Abstract Background Magnetic resonance imaging (MRI) has excellent accuracy in diagnosing preoperative lesions before anal fistula surgery. However, MRI is not good in identifying early recurrent lesions and effective methods for quantitative assessment of fistula healing are still warranted. This retrospective study aimed to develop and validate a specific MRI-based nomogram model to predict fistula healing during the early postoperative period. Methods Patients with complex cryptoglandular anal fistulas who underwent surgery between January 2017 and October 2020 were included in this study. MRI features and clinical parameters were analyzed using univariate and multivariate logistic regression analysis. A nomogram for predicting fistula healing was constructed and validated. Results In total, 200 patients were included, of whom 186 (93%) were male, with a median age of 36 (18–65) years. Of the fistulas, 58.5% were classified as transsphincteric and 19.5% as suprasphincteric. The data were randomly divided into the training cohort and testing cohort at a ratio of 7:3. Logistic analysis revealed that CNR, ADC, alcohol intake history, and suprasphincteric fistula were significantly correlated with fistula healing. These four predictors were used to construct a predictive nomogram model in the training cohort. AUC was 0.880 and 0.847 for the training and testing cohorts, respectively. Moreover, the decision and calibration curves showed high coherence between the predicted and actual probabilities of fistula healing. Conclusions We developed a predictive model and constructed a nomogram to predict fistula healing during the early postoperative period. This model showed good performance and may be clinically utilized for the management of anal fistulas.

In the modern wireless communication system, the manipulation for polarization of electromagnetic wave plays a important role in improving the capacity and reliability of communication. In this paper, a multifunctional polarization converter (MFPC) based on the multilayer reconfigurable metasurface is proposed, which can assist the source antenna to transmit and receive multiple polarization signals. The MFPC consists of a grating which can filter out the undesired polarization and four layers of metasurfaces incorporated with PIN diodes. The functions of the MFPC include LTC and LTL polarization conversions, co-polarization transmission and reflection for arbitrary polarization. By changing the states of PIN diodes, the functions of MFPC can be dynamically switched. Loaded on the aperture of source antenna, the proposed MFPC can serve as a transmissive array with multiple polarization channels, and can also provide EM protection for source antenna by reflecting the incoming interference waves. Cascading of the metasurfaces produces Fabry-Perot resonance in the MFPC, and it contributes to the realization of LTC and LTL polarization conversions. To verify the performance of the proposed MFPC, the prototype is fabricated and tested. The measured results show that the fractional bandwidths of four functions are all higher than 31.9% with transmission or reflection coefficients higher than −2 dB. The frequency band of each function is mainly concentrated in S-band. The measured data are in agreement with the simulated results.