The Chemokine CCL2 Promotes Excitatory Synaptic Transmission in Hippocampal Neurons via GluA1 Subunit Trafficking.

The CC chemokine ligand 2 (CCL2, also known as MCP-1) and its cognate receptor CCR2 have well-characterized roles in chemotaxis. CCL2 has been previously shown to promote excitatory synaptic transmission and neuronal excitability. However, the detailed molecular mechanism underlying this process remains largely unclear. In cultured hippocampal neurons, CCL2 application rapidly upregulated surface expression of GluA1, in a CCR2-dependent manner, assayed using SEP-GluA1 live imaging, surface GluA1 antibody staining, and electrophysiology. Using pharmacology and reporter assays, we further showed that CCL2 upregulated surface GluA1 expression primarily via Gαq- and CaMKII-dependent signaling. Consistently, using i.p. injection of lipopolysaccharide to induce neuroinflammation, we found upregulated phosphorylation of S831 and S845 sites on AMPA receptor subunit GluA1 in the hippocampus, an effect blocked in Ccr2-/- mice. Together, these results provide a mechanism through which CCL2, and other secreted molecules that signal through G-protein coupled receptors, can directly regulate synaptic transmission.

Real-Time Cardiac Abnormality Monitoring and Nursing for Patient using Electrocardiographic Signals.

Introduction Cardiovascular disease care is a critical clinical application that necessitates real-time monitoring models. Previous models required the use of multi-lead signals and could not be customized as needed. Traditional methods relied on manually designed supervised algorithms, based on empirical experience, to identify waveform abnormalities and classify diseases, and were incapable of monitoring and alerting abnormalities in individual waveforms. Methods This research reconstructed the vector model for arbitrary leads using the phase space time delay method, enabling the model to arbitrarily combine signals as needed while possessing adaptive denoising capabilities. After employing automatically constructed machine learning algorithms and designing for rapid convergence, the model can identify abnormalities in individual waveforms and classify diseases, as well as detect and alert on abnormal waveforms. Result Effective noise elimination was achieved, obtaining a higher degree of loss function fitting. Afterwards, the detail differences of the electrocardiogram signal were amplified using a single-lead three-dimensional model. A cropping algorithm was used to remove waveforms severely interfered by external factors. Then, automatic neural network recognition was used. The automatic network generation model was designed effectively for different data types. The accuracy of patient identification is 98.2%, and the accuracy for healthy patients is 99.2%. Conclusion The elastic wavelet neural network can automatically denoise. Through the three-dimensional model, the detailed changes of electrocardiogram signals of different diseases can be observed. The cropping algorithm effectively identified the interfered and destroyed waveforms. The automatic neural network is capable of carrying out disease type classification and patient identity classification.

Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models.

The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019 (COVID-19) immunobiology, often resulting in a lack of reproducibility when extrapolated to the whole organism. Consequently, developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This review summarizes current progress related to COVID-19 animal models, including non-human primates (NHPs), mice, and hamsters, with a focus on their roles in exploring the mechanisms of immunopathology, immune protection, and long-term effects of SARS-CoV-2 infection, as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 infection. Differences among these animal models and their specific applications are also highlighted, as no single model can fully encapsulate all aspects of COVID-19. To effectively address the challenges posed by COVID-19, it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and severities. Optimizing animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic, serving as a robust resource for future emerging infectious diseases.

Subcellular localization of viral proteins after porcine epidemic diarrhea virus infection and their roles in the viral life cycle.

Porcine epidemic diarrhea virus (PEDV) is one of the most devastating diseases affecting the pig industry globally. Due to the emergence of novel strains, no effective vaccines are available for prevention and control. Investigating the pathogenic mechanisms of PEDV may provide insights for creating clinical interventions. This study constructed and expressed eukaryotic expression vectors containing PEDV proteins (except NSP11) with a 3' HA tag in Vero cells. The subcellular localization of PEDV proteins was examined using endogenous protein antibodies to investigate their involvement in the viral life cycle, including endocytosis, intracellular trafficking, genome replication, energy metabolism, budding, and release. We systematically analyzed the potential roles of all PEDV viral proteins in the virus life cycle. We found that the endosome sorting complex required for transport (ESCRT) machinery may be involved in the replication and budding processes of PEDV. Our study provides insight into the molecular mechanisms underlying PEDV infection. IMPORTANCE: The global swine industry has suffered immense losses due to the spread of PEDV. Currently, there are no effective vaccines available for clinical protection. Exploring the pathogenic mechanisms of PEDV may provide valuable insights for clinical interventions. This study investigated the involvement of viral proteins in various stages of the PEDV lifecycle in the state of viral infection and identified several previously unreported interactions between viral and host proteins. These findings contribute to a better understanding of the pathogenic mechanisms underlying PEDV infection and may serve as a basis for further research and development of therapeutic strategies.

A Pt nanoenzyme- and BODIPY-loaded nanoscale covalent organic framework for relieving intratumoural hypoxia to enhance photodynamic therapy.

Herein, we report a composite COF material loaded with a Pt nanoenzyme and an organic photosensitizer BODIPY, synthesized via a stepwise post-synthetic modification. The obtained Pt@COF-BDP nanoparticles can efficiently and continuously convert H2O2 to O2, thereby increasing the efficiency of single-linear oxygen production and achieving efficient tumor inhibition.

Biogated mesoporous silica nanoagents for inhibition of cell migration and combined cancer therapy.

Migration is an initial step in tumor expansion and metastasis; suppressing cellular migration is beneficial to cancer therapy. Herein, we designed a novel biogated nanoagents that integrated the migration inhibitory factor into the mesoporous silica nanoparticle (MSN) drug delivery nanosystem to realize cell migratory inhibition and synergistic treatment. Antisense oligonucleotides (Anti) of microRNA-330-3p, which is positively related with cancer cell proliferation, migration, invasion, and angiogenesis, not only acted as the locker for blocking drugs but also acted as the inhibitory factor for suppressing migration via gene therapy. Synergistic with gene therapy, the biogated nanoagents (termed as MSNs-Gef-Anti) could achieve on-demand drug release based on the intracellular stimulus-recognition and effectively kill tumor cells. Experimental results synchronously demonstrated that the migration suppression ability of MSNs-Gef-Anti nanoagents (nearly 30%) significantly contributed to cancer therapy, and the lethality rate of the non-small-cell lung cancer was up to 70%. This strategy opens avenues for realizing efficacious cancer therapy and should provide an innovative way for pursuing the rational design of advanced nano-therapeutic platforms with the combination of cancer cell migratory inhibition.

Efficacy and safety of apheresis therapy in AQP4 antibody-positive NMOSD attack: A propensity score-matched cohort study.

OBJECTIVE: Plasma exchange (PE) and immunoadsorption (IA) are recognized as effective ways to treat attacks in AQP4 antibody-positive NMOSD, but high-quality evidence was lacking. To evaluate the efficacy and safety of PE/IA plus intravenous methylprednisolone (IVMP) in NMOSD attacks using propensity scores to match IVMP as control. METHODS: Patients were from a prospective observational cohort study. Stratification and interval propensity score matching (PSM) were used to reduce selection bias by matching baseline characteristics (gender, age, time to IVMP, EDSS at attack) between PE/IA + IVMP and IVMP group (in a ratio of 1:2). The primary endpoint of efficacy was EDSS change at 6 months. Adverse events and changes in laboratory tests were recorded. RESULTS: Four hundred and eleven attacks of 336 patients were screened for PSM, and 90 attacks (30 PE/IA + IVMP and 60 IVMP) were included in the analysis. There were significant differences in EDSS [6.25 vs. 6.75; IQR (4.50-8.38 vs. 5.00-8.00), p = 0.671] and visual acuity [median logMAR = 0.35 vs. 1.00; IQR (0.30-0.84 vs. 0.95-1.96), p = 0.002] change between two groups at 6 months. PE/IA + IVMP treatment demonstrated predictive capacity for good recovery as indicated by an area under the curve (AUC) of 0.726. Fibrinogen reduction was found during PE/IA + IVMP treatment [n = 15 (50.00%)], but no severe adverse events led to apheresis treatment discontinuation. DISCUSSION: After PSM analysis, IVMP+PE/IA in acute attack of NMOSD achieved better and continuous improvement in neurological function within 6 months compared with IVMP alone. PE/IA treatment showed a good safety profile.

Nonnegligible Contribution of Nonlymphoid Tissue to Viral Reservoir During the Short-Term Early cART in SIVmac239-Infected Chinese Rhesus Macaques.

HIV/AIDS cannot be cured because of the persistence of the viral reservoir. Because of the complexity of the cellular composition and structure of the human organs, HIV reservoirs of anatomical site are also complex. Recently, although a variety of molecules have been reported to be involved in the establishment and maintenance of the viral reservoirs, or as marker of latent cells, the research mainly focuses on blood and lymph nodes. Now, the characteristics of the viral reservoir in tissue are not yet fully understood. In this study, various tissues were collected from SIVmac239-infected monkeys, and the level of total SIV DNA, SIV 2-LTR DNA, and cell-associated virus RNA in them were compared with character of the anatomical viral reservoir under early treatment. The results showed that short-term combination antiretroviral therapy (cART) starting from 3 days after infection could significantly inhibit viremia and reduce the size of the anatomical viral reservoir, but it could not eradicate de novo infections and ongoing replication of virus. Moreover, the effects of early cART on the level of total SIV DNA, SIV 2-LTR DNA, and cell-associated virus RNA in different tissues were different, which changed the size distribution of viral reservoir in anatomical site. Finally, the contribution of nonlymphoid tissues, especially liver and lung, to the viral reservoir increased after treatment, while the contribution of intestinal lymphoid to the viral reservoir significantly reduced. These results suggested that early treatment effectively decreased the size of viral reservoir, and that the effects of cART on the tissue viral reservoir varied greatly by tissue type. The results implied that persistent existence of virus in nonlymphoid tissues after short-term treatment suggested that the role of nonlymphoid tissues cannot be ignored in development strategies for AIDS therapy.

[Pollution Characteristics, Source Apportionment, and Meteorological Response of Water-soluble Ions in PM2.5 in Xinxiang, North China].

Pollution variation, source characteristics, and meteorological effects of water-soluble inorganic ions (WSIIs) in PM2.5 were analyzed in Xinxiang city, Henan Province. PM2.5 samples and their chemical components were monitored online by using URG-9000 in four seasons:winter (January, 2022), spring (April, 2022), summer (July, 2022), and fall (October, 2022). The results showed that the TWSIIs had the same seasonal fluctuations as PM2.5. The average seasonal concentrations of WSIIs ranged from 19.62-72.15 µg·m-3, accounting for more than 60% of PM2.5, demonstrating that WSIIs were the major components of PM2.5. The annual concentration value of NO3-/SO42- was 2.11, which showed an increasing trend, suggesting predominantly mobile sources for secondary inorganic aerosols (SNA). Further, the molar concentration value [NH4+]/[NO3-] was 1.95, demonstrating that agriculture emissions were the dominant contributors to atmospheric nitrogen. Furthermore, the backward trajectory analysis showed that the concentrations of Ca2+ and Mg2+ were higher when the northeasterly wind prevailed and the wind speed was high. High values of SOR and NOR were correlated with low temperatures and high relative humidity (T < 8℃, RH > 60%), demonstrating that more gaseous precursors were converted into sulfate and nitrate. At high temperatures (T > 24℃), there was no apparent high NOR value like that for SOR, mainly due to the decomposition of NH4NO3 at high temperatures. Finally, backward trajectories associated with the PMF-resolved results were used to explore the regional transport characteristics. The results illustrated that dust sources in the study areas were mainly influenced by air trajectories originating from the northwest regions, whereas secondary sulfate, secondary nitrate, and biomass sources contributed more to WSIIs when wind speed and altitude air masses were low in the area surrounding the observation site.

Core-shell "loading-type" nanomaterials enabling glucometer readout for portable and sensitive detection of p-aminophenol in real samples.

A one-target-many-trigger signal model sensing strategy is proposed for quickly, sensitive and on-site detection of the environmental pollutant p-aminophenol (PAP) by use of a commercial personal glucose meter (PGM) for signal readout with the core-shell "loading-type" nanomaterial MSNs@MnO2 as amplifiable nanoprobes. In this design, the mesoporous silica nanoparticles (MSNs) nanocontainer with entrapped signal molecule glucose is coated with redoxable manganese dioxide (MnO2) nanosheets to form the amplifiable nanoprobes (Glu-MSNs@MnO2). When encountered with PAP, the redox reaction between the MnO2 and PAP can induce the degradation of the outer layer of MSNs@MnO2, liberating multiple copies of the loaded glucose to light up the PGM signal. Owing to the high loading capability of nanocarriers, a "one-to-many" relationship exists between the target and the signal molecule glucose, which can generate adequate signal outputs to achieve the requirement of on-site determination of environmental pollutants. Taking advantage of this amplification mode, the developed PAP assay owns a dynamic linear range of 10.0-400 µM with a detection limit of 2.78 µM and provides good practical application performance with above 96.7 ± 4.83% recovery in environmental water and soil samples. Therefore, the PGM-based amplifiable sensor for PAP proposed can accommodate these requirements of environment monitoring and has promising potential for evaluating pollutants in real environmental samples.

Epigenetic regulation of CD38/CD48 by KDM6A mediates NK cell response in multiple myeloma.

Anti-CD38 monoclonal antibodies like Daratumumab (Dara) are effective in multiple myeloma (MM); however, drug resistance ultimately occurs and the mechanisms behind this are poorly understood. Here, we identify, via two in vitro genome-wide CRISPR screens probing Daratumumab resistance, KDM6A as an important regulator of sensitivity to Daratumumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Loss of KDM6A leads to increased levels of H3K27me3 on the promoter of CD38, resulting in a marked downregulation in CD38 expression, which may cause resistance to Daratumumab-mediated ADCC. Re-introducing CD38 does not reverse Daratumumab-mediated ADCC fully, which suggests that additional KDM6A targets, including CD48 which is also downregulated upon KDM6A loss, contribute to Daratumumab-mediated ADCC. Inhibition of H3K27me3 with an EZH2 inhibitor resulted in CD38 and CD48 upregulation and restored sensitivity to Daratumumab. These findings suggest KDM6A loss as a mechanism of Daratumumab resistance and lay down the proof of principle for the therapeutic application of EZH2 inhibitors, one of which is already FDA-approved, in improving MM responsiveness to Daratumumab.

Susceptibility-weighted image features in AQP4-negative-NMOSD versus MS.

OBJECTIVE: To characterize the susceptibility-weighted image (SWI) features including paramagnetic rim and nodular lesions with signal intensity changes and central vein sign (CVS) associated with aquaporin 4 (AQP4)-immunoglobulin G (IgG)-negative neuromyelitis optica spectrum disorder (NMOSD), and explore whether they can be used as potential imaging biomarkers for differentiating multiple sclerosis (MS) from this disorder. METHODS: We prospectively recruited NMOSD with AQP4-IgG-negative (AQP4- NMOSD) and IgG-positive (AQP4+ NMOSD), and MS subjects from the Clinical and Imaging Patterns of Neuroinflammation Diseases in China (CLUE) project (NCT0410683) between 2019 and 2021. The SWI features including paramagnetic rim and nodular lesions with signal intensity changes and CVS were analyzed and compared among groups, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined for distinguishing MS from AQP4- NMOSD. RESULTS: We enrolled a total of 160 consecutive patients (22 AQP4- NMOSD, 65 AQP4+ NMOSD, and 73 MS). We observed paramagnetic rim lesion (0/120 lesions, 0 %) and nodular (1/120, 1 %) lesions with hypointense signals on SWI in the AQP4- NMOSD group. These characteristics were similar to those recorded from AQP4+ NMOSD patients (rim: 0/369 lesions, 0 %, P = 1.000; nodular: 10/369 lesions, 2.7 %, P = 1.000), but differed significantly from those observed in the MS group (rim: 162/1665 lesions, 9.7 %, P<0.001; nodular: 392/1665 lesions, 23.5 %, P < 0.001). AQP4- NMOSD patients had fewer average CVS+ rate (12 %) than MS patients (46 %, p<0.001), similar to AQP4+ NMOSD (13 %, p = 1.000). The SWI imaging features denoting lesions with paramagnetic rim or nodular hypointense SWI signals showed 90.4 % sensitivity, 95.5 % specificity, 98.5 % PPV, and 75 % NPV, and the criteria with≥3 CVS lesions showed sensitivity of 91.8 %, specificity of 90.9 %%, PPV of 97.1 %, and NPV of 76.9 % in distinguishing MS from AQP4- NMOSD. DISCUSSION: The SWI imaging features including lesions with paramagnetic rim or nodular hypointense SWI signals and 3 CVS lesions carries useful information in distinguishing MS from AQP4- NMOSD.

Efficacy and safety of low- and ultralow-dose rituximab in neuromyelitis optica spectrum disorder.

BACKGROUND: Rituximab effectively targets B cells and reduces relapses in neuromyelitis optica spectrum disorder (NMOSD). But the ideal dosage and treatment intervals remain unanswered. We aimed to assess the efficacy and safety of low and ultralow-dose rituximab in NMOSD. METHODS: We conducted a retrospective analysis of NMOSD patients treated with rituximab at two Chinese tertiary hospitals. Patients received either a low-dose regimen (500 mg reinfusion every 6 months) or an ultralow-dose regimen: 100 to 300 mg rituximab based on CD19+B cells (100 mg for 1-1.5% of peripheral blood mononuclear cells, 200 mg for 1.5-5%, and 300 mg for over 5%). RESULTS: We analyzed data from 136 patients (41 in the low-dose group, 95 in the ultralow-dose group) with median follow-up durations of 43 and 34.2 months, respectively. Both groups exhibited similar sex distribution, age at disease onset, annual relapse rate, and baseline disease duration. Survival analysis showed that ultralow-dose rituximab was noninferior to low-dose rituximab in preventing relapses. Infusion reactions occurred in 20 of 173 (11.6%) low-dose treatments and 9 of 533 (1.7%) ultralow-dose treatments. B-cell re-emergence was observed in 137 of 236 (58.1%) monitors in the low-dose group and 367 of 1136 (32.3%) monitors in the ultralow-dose group. CONCLUSION: Ultralow dose rituximab was noninferior to low-dose rituximab in preventing NMOSD relapses. A randomized controlled trial is essential to validate these findings.

Evaluation of Compressed SENSE on Image Quality and Reduction of MRI Acquisition Time: A Clinical Validation Study.

RATIONALE AND OBJECTIVES: To evaluate the effect of compressed SENSE (CS) in clinical settings on scan time reduction and image quality. MATERIALS AND METHODS: Ninety-five magnetic resonance imaging (MRI) scans from different anatomical regions were acquired, consisting of a standard protocol sequence (SS) and sequence accelerated with CS. Anonymized paired sequences were randomly displayed and rated by six blinded subspecialty radiologists. Side-by-side evaluation on perceived sharpness, perceived signal-to-noise-ratio (SNR), lesion conspicuity, and artifacts were compared and scored on a five-point Likert scale, and individual image quality was evaluated on a four-point Likert scale. RESULTS: CS reduced overall scan time by 32% while maintaining acceptable MRI quality for all regions. The largest time savings were seen in the spine (mean = 68 seconds, 44% reduction) followed by the brain (mean = 86 seconds, 37% reduction). The sequence with maximum time savings was intracranial 3D-time-of-flight magnetic resonance angiography (202 seconds, 56% reduction). CS was mildly inferior to SS on perceived sharpness, perceived SNR, and lesion conspicuity (mean scores = 2.32-2.96, P < .001 [1: SS superior; 3: equivalent; 5: CS superior]). CS was equivalent to SS for joint and body scans on overall image quality (CS = 3.02-3.37, SS = 3.04-3.68, P > .05, [1: lowest quality and 4: highest quality]). The overall image quality of CS was slightly less for brain and spine scans (mean CS = 2.79-3.05, mean SS = 3.13-3.43, P = .021) but still diagnostic. Good overall clinical acceptance for CS (88%) was noted with full clinical acceptance for body scans (100%) and high acceptance for other regions (68%-95%). CONCLUSION: CS significantly reduced MR acquisition time while maintaining acceptable image quality. The implementation of CS may improve departmental workflows and enhance patient care.

Dazhu Hongjingtian Injection for Ischemic Stroke: Protocol for a Prospective, Multicenter Observational Study.

BACKGROUND: Although results from in vitro studies and small randomized controlled trials have shown positive effects of Dazhu hongjingtian injection (DZHJTI) on acute ischemic stroke (AIS), their generalizability to routine clinical practice remains to be established. OBJECTIVE: The primary aim of this study is to evaluate the effectiveness of DZHJTI treatment for AIS with regard to changes in the stroke-related neurological deficit from baseline to outpatient follow-up, mortality, subsequent vascular events, disability, and traditional Chinese medicine syndrome in real-world clinical settings. By monitoring for adverse events or significant changes in vital signs and laboratory parameters, we also aim to assess the safety of DZHJTI. METHODS: This prospective, multicenter cohort study plans to enroll 2000 patients with AIS within 14 days of symptom onset from 30 hospitals across China. Eligible patients will be followed up for 6 months after initiating medication treatments. The primary outcome will be the change in the National Institute of Health Stroke Scale score from baseline to outpatient follow-up. The secondary outcomes include overall mortality, stroke recurrence, new-onset major vascular events, global disability, and improvement of traditional Chinese medicine syndrome in 6 months. Adverse events or clinically significant changes in vital signs and laboratory parameters, regardless of the severity, will be recorded during the trial to assess the safety of DZHJTI. An augmented inverse propensity weighted estimator will be used to reduce variability and improve accuracy in average treatment effects estimation. RESULTS: The clinical trial registration was approved in October 2022, and the recruitment and enrollment of participants started in November 2022. The study's outcomes are expected to be published in 2025 in reputable, peer-reviewed health-related research journals. CONCLUSIONS: This real-world cohort study is the first to assess the effectiveness and safety of DZHJTI in treating AIS. It may provide additional clinical evidence, including the duration of response, long-term drug effectiveness, and subgroup efficacy data. The study results will be valuable for clinicians and patients seeking optimal treatment for AIS and could lead to better use of DZHJTI and improved patient outcomes. TRIAL REGISTRATION: ITMCTR ITMCTR2022000005; http://tinyurl.com/554ns8m5. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52447.

FAM171B stabilizes vimentin and enhances CCL2-mediated TAM infiltration to promote bladder cancer progression.

BACKGROUND: Invasion and metastasis are the main causes of unfavourable prognosis in patients diagnosed with bladder cancer. The efficacy of immunotherapy in bladder cancer remains suboptimal due to the presence of an immunosuppressive microenvironment. The novel protein family with sequence similarity 171B (FAM171B) has been identified, but its precise role and mechanism in bladder cancer remain unclear. METHODS: In this study, we conducted an analysis to investigate the associations between FAM171B expression and the prognosis and clinicopathological stage of bladder cancer. To this end, we utilized RNA sequencing data from the TCGA and GEO databases, as well as tumor tissue specimens obtained from our clinical centre. RNA sequencing analysis allowed us to examine the biological function of FAM171B at the transcriptional level in bladder cancer cells. Additionally, we used immunoprecipitation and mass spectrometry to identify the protein that interacts with FAM171B in bladder cancer cells. The effects of FAM171B on modulating tumor-associated macrophages (TAMs) and vimentin-mediated tumor progression, as well as the underlying mechanisms, were clarified by phalloidin staining, immunofluorescence staining, ELISA, RNA immunoprecipitation, flow cytometry and a bladder cancer graft model. RESULTS: FAM171B expression exhibits strong positive correlation with poor survival outcomes and advanced clinicopathological stages in patients with bladder cancer. FAM171B significantly promoted bladder cancer growth and metastasis, accompanied by TAM accumulation in the microenvironment, in vivo and in vitro. Through studies of the molecular mechanism, we found that FAM171B contributes to tumor progression by stabilizing vimentin in the cytoplasm. Additionally, our research revealed that FAM171B enhances the splicing of CCL2 mRNA by interacting with heterogeneous nuclear ribonucleoprotein U (HNRNPU), ultimately leading to increased recruitment and M2 polarization of TAMs. CONCLUSIONS: In this study, we identified FAM171B as a potent factor that promotes the progression of bladder cancer. These findings establish a solid theoretical foundation for considering FAM171B as a potential diagnostic and therapeutic biomarker for bladder cancer.

Significant increase of the photoresponse range and conductivity for a chalcogenide semiconductor by viologen coating through charge transfer.

Widening the photoresponse range while enhancing the electrical properties of semiconductors could reduce the complexity and cost of photodetectors or increase the power conversion efficiency of solar cells. Surface doping through charge transfer with organic species is one of the most effective and widely used approaches to achieve this aim. It usually features easier preparation over other doping methods but is still limited by the low physicochemical stability and high cost of the used organic species or low improvement of electrical properties. This work shows unprecedented surface doping of semiconductors with highly stable, easily obtained, and strong electron-accepting viologen components, realizing the significant improvement of both the photoresponse range and conductivity. Coating the chalcogenide semiconductor KGaS2 with dimethyl viologen dichloride (MV) yields a charge-transfer complex (CTC) on the surface, which broadens the photoresponse range by nearly 300 nm and improves the conductivity by 5 orders of magnitude. The latter value surpasses all records obtained by surface doping through charge transfer with organic species.

Integrated single-cell and spatial transcriptomics reveals heterogeneity of fibroblast and pivotal genes in psoriasis.

Psoriasis, which is one of the most common skin diseases, involves an array of complex immune constituents including T cells, dendritic cells and monocytes. Particularly, the cytokine IL17A, primarily generated by TH17 cells, assumes a crucial function in the etiology of psoriasis. In this study, a comprehensive investigation utilizing bulk RNA analysis, single-cell RNA sequencing, and spatial transcriptomics was employed to elucidate the underlying mechanisms of psoriasis. Our study revealed that there is an overlap between the genes that are differentially expressed in psoriasis patients receiving three anti-IL17A monoclonal antibody drugs and the genes that are differentially expressed in lesion versus non-lesion samples in these patients. Further analysis using single-cell and spatial data from psoriasis samples confirmed the expression of hub genes that had low expressions in psoriasis tissue but were up-regulated after anti-IL17A treatments. These genes were found to be associated with the treatment effects of brodalumab and methotrexate, but not adalimumab, etanercept, and ustekinumab. Additionally, these genes were predominantly expressed in fibroblasts. In our study, fibroblasts were categorized into five clusters. Notably, hub genes exhibited predominant expression in cluster 3 fibroblasts, which were primarily engaged in the regulation of the extracellular matrix and were predominantly located in the reticular dermis. Subsequent analysis unveiled that cluster 3 fibroblasts also established communication with epithelial cells and monocytes via the ANGPTL-SDC4 ligand-receptor configuration, and their regulation was governed by the transcription factor TWIST1. Conversely, cluster 4 fibroblasts, responsible for vascular endothelial regulation, were predominantly distributed in the papillary dermis. Cluster 4 predominantly engaged in interactions with endothelial cells via MDK signals and was governed by the distinctive transcription factor, ERG. By means of an integrated analysis encompassing bulk transcriptomics, single-cell RNA sequencing, and spatial transcriptomics, we have discerned genes and clusters of fibroblasts that potentially contribute to the pathogenesis of psoriasis.

Promoting ordering degree of intermetallic fuel cell catalysts by low-melting-point metal doping.

Carbon supported intermetallic compound nanoparticles with high activity and stability are promising cathodic catalysts for oxygen reduction reaction in proton-exchange-membrane fuel cells. However, the synthesis of intermetallic catalysts suffers from large diffusion barrier for atom ordering, resulting in low ordering degree and limited performance. We demonstrate a low-melting-point metal doping strategy for the synthesis of highly ordered L10-type M-doped PtCo (M = Ga, Pb, Sb, Cu) intermetallic catalysts. We find that the ordering degree of the M-doped PtCo catalysts increases with the decrease of melting point of M. Theoretic studies reveal that the low-melting-point metal doping can decrease the energy barrier for atom diffusion. The prepared highly ordered Ga-doped PtCo catalyst exhibits a large mass activity of 1.07 A mgPt-1 at 0.9 V in H2-O2 fuel cells and a rated power density of 1.05 W cm-2 in H2-air fuel cells, with a Pt loading of 0.075 mgPt cm-2.