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This study aims to integrate a convolutional neural network (CNN) and the Random Forest Model into a rehabilitation assessment device to provide a comprehensive gait analysis in the evaluation of movement disorders to help physicians evaluate rehabilitation progress by distinguishing gait characteristics under different walking modes. Equipped with accelerometers and six-axis force sensors, the device monitors body symmetry and upper limb strength during rehabilitation. Data were collected from normal and abnormal walking groups. A knee joint limiter was applied to subjects to simulate different levels of movement disorders. Features were extracted from the collected data and analyzed using a CNN. The overall performance was scored with Random Forest Model weights. Significant differences in average acceleration values between the moderately abnormal (MA) and severely abnormal (SA) groups (without vehicle assistance) were observed (p < 0.05), whereas no significant differences were found between the MA with vehicle assistance (MA-V) and SA with vehicle assistance (SA-V) groups (p > 0.05). Force sensor data showed good concentration in the normal walking group and more scatter in the SA-V group. The CNN and Random Forest Model accurately recognized gait conditions, achieving average accuracies of 88.4% and 92.3%, respectively, proving that the method mentioned above provides more accurate gait evaluations for patients with movement disorders.

In lumbar puncture surgery, compared with the conventional methodologies like computed tomography and magnetic resonance imaging, ultrasound imaging offers the advantages of being low cost, no radiation and real-time image generation. However, the use of ultrasound equipment in lumbar puncture involves a cumbersome and time-consuming process for the subjective imaging of the overall structure of the lumbar spine in order to determine the exact puncture point and path. Meanwhile, the robotic arm puncture system has the advantages of high precision, good stability and simple and efficient operation. As a result, robotic-assisted ultrasound scanning is valuable for the assessment of a puncture path in spinal tap surgery. In this pursuit, based on the official URSDK development package for a robot arm and the Transmission Control Protocol/Internet Protocol, the system proposed in the present study involves a program to control the robot arm to clamp down onto an ultrasonic probe to enable automatic scanning and acquisition of images. A three-dimensional reconstruction program based on the visualization toolkit was designed, and a lumbar spine experiment was conducted with this system. A total of 136 two-dimensional ultrasound images were collected in the lumbar spine model experiment by enhancing contrast of and denoising the original ultrasound images, and a linear interpolation algorithm was used to perform the three-dimensional reconstruction of the lumbar spine model. The reconstructed structure was defective, but the location of the spinous process gap was determined with the sagittal and coronal images. The feasibility of the system was verified by the reconstruction results, which can provide a reference for determining the puncture point and path planning in the lumbar puncture surgery.

Previous study demonstrated that Chang Run Tong (CRT) could partly restore the colon remodeling in streptozotocin- (STZ-) induced diabetic rats. Here we investigated the mechanisms of such effects of CRT. Diabetes was induced by a single injection of 40 mg/kg of STZ. CRT was poured into the stomach by gastric lavage once daily for 60 days. The remodeling parameters were obtained from diabetic (DM), CRT treated diabetic (T1, 50 g/kg; T2, 25 g/kg), and normal (Con) rats. Expressions of advanced glycation end product (AGE), AGE receptor, transforming growth factor-β1 (TGF-β1), and TGF-β1 receptor in the colon wall were immunochemically detected and quantitatively analyzed. The association between the expressions of those proteins and the remodeling parameters was analyzed. The expressions of those proteins were significantly higher in different colon layers in the DM group (P0.05). The corrective effect on the expressions of those proteins is likely to be one molecular pathway for the improvement of CRT on the diabetes-induced colon remodeling.

Background: The long-term effects of extracorporeal shockwave therapy (ESWT) on rotator cuff repair are unknown. Objectives: To investigate the functional outcomes and structural changes of ESWT at 3-year follow-up after rotator cuff repair. Methods: A randomized clinical trial was conducted, including patients who underwent rotator cuff repair. The patients were assigned to two groups based on whether they underwent radial ESWT 3 months postoperatively. The ESWT Group received 5 weeks of rehabilitation and ESWT weekly, whereas the CONTROL Group received only rehabilitation. Visual analog scale (VAS) pain score and functional scores were analyzed at 3 months (baseline), 6 months, and 3 years follow-up. In addition, MRI and ultrasonography were used to assess tendon maturation, integrity, tendon quality, acromiohumeral distance (AHD), and muscle fatty infiltration. Results: Finally, 32 participants completed all the assessments. At the final follow-up, 2 patients in the ESWT Group (16.5 %) versus one patient in the CONTROL Group (6.25 %) had rotator cuff failure (P = 0.176). The ESWT treatment showed similar clinical outcomes in VAS-pain score, functional scores, tendon quality, AHD, and muscle fatty infiltration versus the CONTROL Group (Ps > 0.05). MRI analysis indicated improved tendon healing after ESWT treatment at both 6-month (P = 0.036) and 3-year follow-up (P = 0.028). Conclusion: Early intervention with radial ESWT sustained long-term effects on the healing of the repaired rotator cuff and similar functional outcomes at long-term follow-up compared with standard rehabilitation.

Abstract Background Lymph node (LN) metastasis is a significant prognostic factor for esophageal squamous cell carcinoma (ESCC), and there are no satisfactory methods for accurately predicting metastatic LNs. The present study aimed to assess the efficacy of 99mTc‐3PRGD2 single‐photon emission computed tomography (SPECT)/computed tomography (CT) for diagnosing metastatic LNs in ESCC. Methods A total of 15 enrolled patients with ESCC underwent 99mTc‐3PRGD2 SPECT/CT and 18F‐fluorodeoxyglucose positron emission tomography‐computed tomography (18F‐FDG PET/CT) examinations preoperatively. High‐definition bone carving reconstruction technology (HD‐xSPECT Bone) was applied to quantitatively assess the LN's SUVmax via SPECT/CT. The two methods were compared for diagnosing metastatic LNs with pathology as the gold standard. Results Among 15 patients, 23 metastatic lymph node stations (mLNSs) were predicted by SPECT/CT, with a mean SUVmax of 2.71 ± 1.34, of which 15 were pathologically confirmed; 32 mLNSs were predicted by PET/CT with a mean SUVmax of 4.41 ± 4.02, of which 17 were pathologically confirmed. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of SPECT/CT for diagnosing metastatic LNs were 62.50%, 91.30%, 85.34%, 65.22%, and 90.32%, respectively, and those of PET/CT were 70.83%, 83.70%, 81.03%, 53.13%, and 91.67%, respectively. There was no significant difference in sensitivity (p = 0.061) or specificity (p = 0.058) between the two methods. The AUCSPECT/CT was 0.816 and the SUVmax threshold was 2.5. Conclusion 99mTc‐3PRGD2 SPECT/CT might be an effective method for diagnosing metastatic LNs in ESCC, especially in combination with HD‐xSPECT Bone. The diagnostic efficiency of this method was noninferior to that of 18F‐FDG PET/CT. The SUVmax threshold of 2.5 showed the highest agreement with the pathology findings.

Abstract Prostate cancer, one of the most prevalent malignancies among men worldwide, is intricately linked with androgen signaling, a key driver of its pathogenesis and progression. Understanding the diverse expression patterns of androgen-responsive genes holds paramount importance in unraveling the biological intricacies of this disease and prognosticating patient outcomes. In this study, utilizing consensus clustering analysis based on the expression profiles of androgen-responsive genes, prostate cancer patients from the TCGA database were stratified into two distinct subtypes, denoted as C1 and C2. Notably, the C1 subtype demonstrates a significant upregulation of certain genes, such as CGA and HSD17B12, along with a shorter progression-free survival duration, indicating a potentially unfavorable prognosis. Further analyses elucidated the immune infiltration disparities, mutation landscapes, and gene functional pathways characteristic of each subtype. Through integrated bioinformatics approaches and machine learning techniques, key genes such as BIRC5, CENPA, and MMP11 were identified as potential therapeutic targets, providing novel insights into tailored treatment strategies. Additionally, single-cell transcriptome analysis shed light on the heterogeneous expression patterns of these genes across different cell types within the tumor microenvironment. Furthermore, virtual screening identified candidate drugs targeting the BIRC5 receptor, offering promising avenues for drug development. Collectively, these findings deepen our understanding of prostate cancer biology, paving the way for personalized therapeutic interventions and advancing the quest for more effective treatments in prostate cancer management.

Objective To investigate the feasibility of leucocyte-reduced pooled platelet concentrates from whole blood stored at 4℃, and provide theoretical basis for the components preparation. Methods The collected 400 mL ACD-B anticoagulant whole blood was randomly divided into two groups, stored at 4℃ and room temperature. The buffy coat was prepared within 6 hours and store at 22℃ until next day to prepare leucocyte-reduced pooled platelet concentrates. Platelet samples on day 1, 3, 5 and 7 were taken for the blood cell count and related parameter detection. The pH, glucose and lactic acid content were determined to reflect the metabolic status, and the thromboelastography, platelet aggregation rate and PAC-1 and CD62P expression were determined to reflect the function and activation of platelets. The difference in platelets between two groups were analyzed. Results With the extension of storage time, the count of leucocyte-reduced pooled platelet concentrates decreased gradually, but the platelets distribution width (PDW), mean platelet volume (MPV) and platelet-larger cell ratio (P-LCR) increased gradually in two groups, with no statistical significance (P>0.05).The pH and glucose contents in two groups gradually decreased, but the lactic acid content gradually increased, with no significant difference (P>0.05). The thrombelastogram showed MA value that reflecting platelet function has no significant change during the storage, and there was no significant difference between the two groups (P>0.05). The aggregation rates decreased while the expression of PAC-1 and CD62P increased gradually with the prolongation of preservation time, with no significant difference between the two groups (P>0.05). Conclusion There is no significant difference in platelet count, function and activation between whole blood stored at 4℃ and at room temperature within 6 hours. Whole blood stored at 4℃ within 6 hours can be considered as the raw material for leucocyte-reduced pooled platelet concentrates.

Abstract Melanin-concentrating hormone (MCH) is a cyclic neuropeptide that regulates food intake, energy balance, and other physiological functions by stimulating MCHR1 and MCHR2 receptors, both of which are class A G protein-coupled receptors. MCHR1 predominately couples to inhibitory G protein, Gi/o, and MCHR2 can only couple to Gq/11. Here we present cryo-electron microscopy structures of MCH-activated MCHR1 with Gi and MCH-activated MCHR2 with Gq at the global resolutions of 3.01 Å and 2.40 Å, respectively. These structures reveal that MCH adopts a consistent cysteine-mediated hairpin loop configuration when bound to both receptors. A central arginine from the LGRVY core motif between the two cysteines of MCH penetrates deeply into the transmembrane pocket, triggering receptor activation. Integrated with mutational and functional insights, our findings elucidate the molecular underpinnings of ligand recognition and MCH receptor activation and offer a structural foundation for targeted drug design.

The global rate of Amphotericin B (AmB) resistance in Candida auris has surpassed 12%. However, there is limited data on available clinical treatments and microevolutionary analyses concerning reduced AmB sensitivity. In this study, we collected 18 C. auris isolates from five patients between 2019 and 2022. We employed clinical data mining, genomic, and transcriptomic analyses to identify genetic evolutionary features linked to reduced AmB sensitivity in these isolates during clinical treatment. We identified six isolates with a minimum inhibitory concentration (MIC) of AmB below 0.5 µg/mL (AmB0.5) and 12 isolates with an AmB-MIC of 1 µg/mL (AmB1) or ≥ 2 µg/mL (AmB2). All five patients received 24-hour AmB (5 mg/L) bladder irrigation treatment. Evolutionary analyses revealed an ERG3 (c923t) mutation in AmB1 C. auris. Additionally, AmB2 C. auris was found to contain a t2831c mutation in the RAD2 gene. In the AmB1 group, membrane lipid-related gene expression (ERG1, ERG2, ERG13, and ERG24) was upregulated, while in the AmB2 group, expression of DNA-related genes (e.g. DNA2 and PRI1) was up-regulated. In a series of C.auris strains with reduced susceptibility to AmB, five key genes were identified: two upregulated (IFF9 and PGA6) and three downregulated (HGT7, HGT13,and PRI32). In this study, we demonstrate the microevolution of reduced AmB sensitivity in vivo and further elucidate the relationship between reduced AmB sensitivity and low-concentration AmB bladder irrigation. These findings offer new insights into potential antifungal drug targets and clinical markers for the “super fungus”, C. auris.

Introduction: Drug resistance to echinocandins, first-line drugs used to treat Candida auris infection, is rapidly emerging. However, the accumulation of mutations in genes other than FKS1 (before an isolate develops to resistance via FKS1 mutations), remains poorly understood. Methods: Four clinical cases and 29 isolates associated with the incremental process of echinocandin resistance were collected and analyzed using antifungal drug susceptibility testing and genome sequencing to assess the evolution of echinocandin resistance. Findings: Six echinocandin minimum inhibitory concentration (MIC)-elevated C. auris strains and seven resistant strains were isolated from the urinary system of patients receiving echinocandin treatment. Meanwhile, phylogenetic analyses illustrated that the echinocandin-resistant strains were closely related to other strains in the same patient. Genomic data revealed that the echinocandin-resistant strains had FKS1 mutations. Furthermore, three categories (ECN-S/E/R) of non-synonymous mutant SNP genes (such as RBR3, IFF6, MKC1, MPH1, RAD2, and MYO1) in C. auris appeared to be associated with the three-stage-evolutionary model of echinocandin resistance in C. glabrata: cell wall stress, drug adaptation, and genetic escape (FKS mutation). Interpretation: Echinocandin-resistant C. auris undergoes spatial and temporal phase changes closely related to echinocandin exposure, particularly in the urinary system. These findings suggest that FKS1 mutations mediate an evolutionary accumulation of echinocandin resistance followed by modulation of chromosome remodelling and DNA repair processes that ultimately lead to FKS1 hot spot mutations and the development of drug resistance. This study provides an in-depth exploration of the molecular pathways involved in the evolution of Candida auris echinocandin resistance.

The main objective of this study was to examine the integration of indigenous knowledge (IK) into the rapidly developing field of rural social work in China. The study demonstrated the incorporation of indigenous elements such as folkways, power structures, values, norms, traditions, and crafts into the practice through collaboration with the local community. The research employed purposive sampling, which included 4 agency directors, 1 head of a social work organization, 6 social workers, 21 social work students, 16 children and teenagers, 13 villagers, 1 folk writer, 5 local families, 3 teacher lecturers, and 6 government officers. Results showed that the integration process involves the identification, extraction, application, and evaluation of IK are closely linked to the indigenous environment, service recipients, and social workers. Nevertheless, further research is required to operationalize and evaluate the effectiveness of this integration. Findings would be important guidelines for policymakers, education and development experts, and service providers. The conclusions drawn from this study offer valuable insights into the effective integration of Indigenous Knowledge (IK) into social work practice. These insights hold significance for policymakers, education and development experts, as well as service providers not only in China but also in a broader international context.

IntroductionHIV molecular network based on genetic distance (GD) has been extensively utilized. However, the GD threshold for the non-B subtype differs from that of subtype B. This study aimed to optimize the GD threshold for inferring the CRF01_AE molecular network.MethodsNext-generation sequencing data of partial CRF01_AE pol sequences were obtained for 59 samples from 12 transmission pairs enrolled from a high-risk cohort during 2009 and 2014. The paired GD was calculated using the Tamura-Nei 93 model to infer a GD threshold range for HIV molecular networks.Results2,019 CRF01_AE pol sequences and information on recent HIV infection (RHI) from newly diagnosed individuals in Shenyang from 2016 to 2019 were collected to construct molecular networks to assess the ability of the inferred GD thresholds to predict recent transmission events. When HIV transmission occurs within a span of 1-4 years, the mean paired GD between the sequences of the donor and recipient within the same transmission pair were as follow: 0.008, 0.011, 0.013, and 0.023 substitutions/site. Using these four GD thresholds, it was found that 98.9%, 96.0%, 88.2%, and 40.4% of all randomly paired GD values from 12 transmission pairs were correctly identified as originating from the same transmission pairs. In the real world, as the GD threshold increased from 0.001 to 0.02 substitutions/site, the proportion of RHI within the molecular network gradually increased from 16.6% to 92.3%. Meanwhile, the proportion of links with RHI gradually decreased from 87.0% to 48.2%. The two curves intersected at a GD of 0.008 substitutions/site.DiscussionA suitable range of GD thresholds, 0.008-0.013 substitutions/site, was identified to infer the CRF01_AE molecular transmission network and identify HIV transmission events that occurred within the past three years. This finding provides valuable data for selecting an appropriate GD thresholds in constructing molecular networks for non-B subtypes.

Low-level viremia (LLV) ranging from 50 to 1,000 copies/ml is common in most HIV-1-infected patients receiving antiretroviral therapy (ART). However, the source of LLV and the impact of LLV on the HIV-1 reservoir during ART remain uncertain. We hypothesized that LLV may arise from the HIV reservoir and its occurrence affect the composition of the reservoir after LLV episodes. Accordingly, we investigated the genetic linkage of sequences obtained from plasma at LLV and pre-ART time points and from peripheral blood mononuclear cells (PBMCs) at pre-ART, pre-LLV, LLV, and post-LLV time points. We found that LLV sequences were populated with a predominant viral quasispecies that accounted for 67.29%∼100% of all sequences. Two episodes of LLV in subject 1, spaced 6 months apart, appeared to have originated from the stochastic reactivation of latently HIV-1-infected cells. Moreover, 3.77% of pre-ART plasma sequences were identical to 67.29% of LLV-3 plasma sequences in subject 1, suggesting that LLV may have arisen from a subset of cells that were infected before ART was initiated. No direct evidence of sequence linkage was found between LLV viruses and circulating cellular reservoirs in all subjects. The reservoir size, diversity, and divergence of the PBMC DNA did not differ significantly between the pre- and post-LLV sampling points (P > 0.05), but the composition of viral reservoir quasispecies shifted markedly before and after LLV episodes. Indeed, subjects with LLV had a higher total PBMC DNA level, greater viral diversity, a lower proportion of variants with identical sequences detected at two or more time points, and a shorter variant duration during ART compared with subjects without LLV. Overall, our findings suggested that LLV viruses may stem from an unidentified source other than circulating cellular reservoirs. LLV episodes may introduce great complexity into the HIV reservoir, which brings challenges to the development of treatment strategies.

Given the escalating potential risk associated with X-ray radiation exposure to patients, scholars have been dedicated to investigating advanced algorithms for low-dose CT (LDCT) imaging. The utilization of Generative Adversarial Networks (GANs) has gained significant traction in the field of LDCT denoising research over the past few years, owing to its notable performance advantages. However, variations in the distribution intensity of noise and artifacts in the LDCT image can compromise the robustness and denoising performance of GAN. In this paper, we propose a scale-sensitive generative adversarial network to enhance the robustness of GAN used in LDCT denoising. Our proposed network incorporates an error feedback pyramid generator to improve the denoising network’s sensitivity towards noise and artifacts present in LDCT images by performing feature extraction and noise reduction at different scales. Additionally, we introduce a multi-scale residual discriminator with a wider receptive field and stronger feature extraction ability to enhance the discrimination between true and false samples. Furthermore, specific constraints are incorporated into the loss functions based on the network structure, thereby enhancing the effect of adversarial training between the error feedback pyramid generator and multi-scale residual discriminator while improving the performance of the denoising network. Experimental results demonstrate that our proposed network outperforms state-of-the-art methods in terms of artifact suppression, structural preservation, and model generalization capability for LDCT denoising.

Abstract Damage to lamellar keratinocytes, an essential cellular component of the epidermal layer of hoof tissue, can have a detrimental effect on hoof health and the overall production value of dairy cows. We isolated and cultured cow lamellar keratinocytes using the Dispase II and collagenase methods. We purified them by differential digestion and differential velocity adherent methods at each passaging and identified them by keratin 14 immunofluorescence. We established an in vitro model of inflammation in laminar keratinocytes using LPS and investigated whether chicoric acid protects against inflammatory responses by inhibiting the activation of the TLR4/MAPK/NF-κB signaling pathway. The results showed that cow lamellar keratinocytes were successfully isolated and cultured by Dispase II combined with the collagenase method. In the in vitro inflammation model established by LPS, the Chicoric acid decreased the concentration of inflammatory mediators (TNF-α, IL-1β, and IL-6), down-regulated the mRNA expression of TLR4 and MyD88 (P

Abstract Introduction Evidence on the willingness of men who have sex with men (MSM) with oral pre-exposure prophylaxis (PrEP) experience, especially those with suboptimal adherence, to take long-acting injectable PrEP (LAI-PrEP) is critical to guide future LAI-PrEP implementation. Objective The objective was to assess the willingness of MSM with oral PrEP experience to take LAI-PrEP. Methods MSM who participated in the China Real-world Study of Oral PrEP (CROPrEP) were enrolled in this study. Information on the willingness of MSM to take LAI-PrEP and potential correlates was collected using a structured online questionnaire. The main outcomes were the willingness of MSM to take LAI-PrEP and its association with HIV-related behaviours, sexually transmitted infections, and oral PrEP history. Logistic regression was used to identify correlates of the willingness of MSM to take LAI-PrEP. Results A total of 612 former CROPrEP participants (FCPs) were included in this study. There were 315 (51.5%) daily oral PrEP (D-PrEP) users and 297 (48.5%) event-driven oral PrEP (ED-PrEP) users at the last follow-up. Most FCPs (77.8%) were willing to take free LAI-PrEP. FCPs with no less than two sexual male partners (aOR = 1.54, [95% CI: 1.04, 2.29], P = 0.031), those with male partners with unknown HIV statuses (aOR = 2.04, [95% CI: 1.31, 3.18], P = 0.002), those with recreational drug use (aOR = 1.58, [95% CI: 1.05, 2.40], P = 0.030), and those with HSV-2 positivity (aOR = 2.15, [95% CI: 1.30, 3.57], P = 0.003) were more willing to take LAI-PrEP, while ED-PrEP users (aOR = 0.66, [95% CI: 0.45, 0.98], P = 0.037) and FCPs with suboptimal oral PrEP adherence (aOR = 0.58, [95% CI: 0.36, 0.94], P = 0.026) were less willing to take LAI-PrEP. Conclusion LAI-PrEP has good prospects for expanding PrEP coverage. However, FCPs with suboptimal oral PrEP adherence are less likely to take LAI-PrEP. Further intervention and implementation efforts are needed to improve the willingness of MSM to use LAI-PrEP, and sexual health should be considered during the discussion about PrEP initiation.

Sepsis is a common and deadly syndrome that despite all the progress in its control, the death rate caused by it is high. Sepsis is a serious problem that needs immediate attention and treatment. This infection, especially if it is caused by bacteria resistant to several drugs, causes high mortality. About two-thirds of sepsis cases occur in hospitalized patients. Several factors such as increasing the age of the population, increasing the duration of chronic diseases, high consumption of antibiotics and corticosteroids, use of mechanical devices and intravascular devices play a role in increasing its incidence. We herein demonstrate the biogenic procedure for the in situ immobilizing gold nanoparticles over lignin (Lig)-modified Fe3O4 magnetic nanoparticles mediated by Cydonia leaf extract (Fe3O4@Lig-Ag NPs) and its catalytic activity on the acetylation of alcohols using acetic anhydride and subsequent biological performances. The successful synthesis of Fe3O4@Lig-Ag NPs was assessed using an array of advanced techniques like field emission scanning electron microscopy, fourier transformed infrared spectroscopy, transmission electron microscopy EDX, elemental mapping, vibrating-sample magnetometer, and X-ray diffraction. Cecal ligation and puncture was used for inducing the sepsis model in rats. Several doses of Fe3O4@Lig-Ag NPs (45, 15, and 5 µg/kg) on oxidant–antioxidant, inflammatory mediators mRNA such as IL-1 and TNF-α, and its effects on the levels of expression were assessed in the kidney, liver, duodenum, lung, and stomach. When septic rats kidney, liver, duodenum, lung, and stomach were compared with those of the control group, it was found that Fe3O4@Lig-Ag NPs dose-dependent administration raised glutathione levels and superoxide dismutase activity and significantly reduced the levels of malondialdehyde. The Fe3O4@Lig-Ag NPs (45 µg/kg) indicated greater anti-oxidative effects than the 5 and 15 µg/kg doses for all the assessed parameters. In addition, the expression of TNF-α mRNA in the CLP + 45 µg/kg group was decreased in comparison with the control group. Fe3O4@Lig-Ag NPs reduced oxidative stress by enhancing the free radicals scavenging effects and supporting endogenous antioxidants. The Fe3O4@Lig-Ag NPs potent antioxidant property may be related to the cytokine cascade suppression during sepsis. The above findings offer that Fe3O4@Lig-Ag NPs administration may indicate a modern treatment for the inhibition of liver, kidney, lung, duodenum, and stomach tissues damage caused by septic conditions.

Abstract Background Natural killer (NK) cells play an important first-line role against tumour and viral infections and are regulated by inhibitory receptor expression. Among these inhibitory receptors, the expression, function, and mechanism of cluster of differentiation 47 (CD47) on NK cells during human immunodeficiency virus (HIV) infection remain unclear. Methods Fresh peripheral blood mononuclear cells (PBMCs) were collected from people living with HIV (PLWH) and HIV negative controls (NC) subjects. Soluble ligand expression levels of CD47 were measured using ELISA. HIV viral proteins or Toll-like receptor 7/8 (TLR7/8) agonist was used to investigate the mechanisms underlying the upregulation of CD47 expression. The effect of CD47 on NK cell activation, proliferation, and function were evaluated by flow cytometry. RNA-seq was used to identify downstream pathways for CD47 and its ligand interactions. A small molecule inhibitor was used to restore the inhibition of NK cell function by CD47 signalling. Results CD47 expression was highly upregulated on the NK cells from PLWH, which could be due to activation of the Toll-like receptor 7/8 (TLR7/8) pathway. Compared with NC subjects, PLWH subjects exhibited elevated levels of CD47 ligands, thrombospondin-1 (TSP1), and counter ligand signal regulatory protein-α (SIRPα). The TSP1–CD47 axis drives the suppression of interferon gamma (IFN-γ) production and the activation of the Janus kinase signal transducer and activator of transcription (JAK–STAT) pathway in NK cells. After treatment with a STAT3 inhibitor, the NK cells from PLWH showed significantly improved IFN-γ production. Conclusions The current data indicate that the binding of the inhibitory receptor CD47 to plasma TSP1 suppresses NK cell IFN-γ production by activating the JAK/STAT3 pathway during HIV infection. Our results suggest that CD47 and its related signalling pathways could be targets for improving NK cell function in people living with HIV.

Being an alien species, Spartina alterniflora has occupied the living space of native animals and plants, causing irreversible damage to the environment. Converting Spartina alterniflora into carbon or its derivatives offers a valuable solution to manage both invasive biomass and an energy shortage. Herein, through a simple activation process, we successfully prepared Spartina alterniflora-derived carbon (SAC) and its N-doped derivative SANC, and used them as metal-free catalysts for an oxygen reduction reaction (ORR). SAC exhibits good electrochemical performance and holds significant potential in catalysis. After N-doping by melamine as a nitrogen source, electronegativity is redistributed in SANC, leading to enhanced performance (a half-wave potential of 0.716 V vs. RHE, and a four-electron transfer pathway with a H2O2 yield of only 2.05%). This work presents a straightforward and cost-effective approach to the usage of obsolete invasive biomass and shows great potential in energy generation.