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2.
Food Chem ; 459: 140339, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38986206

ABSTRACT

A facile, fast and visible sensing platform for ascorbic acid (AA) detection has been developed based on self-assembled hydrangea-like europium metal-organic framework (HL-EuMOF). HL-EuMOF was synthesized through a simple one-step mixing process with Eu3+ and 1, 10-phenanthroline-2, 9-dicarboxylic acid at room temperature, which exhibited excellent properties including strong red fluorescence, long decay lifetime (548.623 µs) and good luminescent stability. Based on the specific redox reaction between Fe3+ and AA, the HL-EuMOF@Fe3+ was fabricated with "turn-off" response for AA, where the resulting Fe2+ displayed effective fluorescence quenching ability toward HL-EuMOF. The sensor demonstrated low detection limit (31.94 nM), rapid response time (30 s) and high selectivity. Integration of smartphone-assisted RGB analysis with HL-EuMOF@Fe3+ permitted convenient and visible quantitative determination of AA level. This approach also presented good detection performances in complex human serum and beverage samples, which could provide a valuable tool for AA detection in biomedical research and food industry.

3.
Int J Biol Macromol ; 275(Pt 2): 133704, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38972655

ABSTRACT

To identify the key amino acids (AAs) affecting the allergenicity of hemocyanin (HC) allergens from Chinese mitten crabs, in this study, two epitopes, P1-SHFTGSKSNPEQR and P2-LSPGANTITR were employed and four potential key AAs (P1: F3 and N9 and P2: N6 and R10) were predicted. Mast cell and mouse models revealed that four mutants induced lower levels of immunoglobulin E (IgE) and Th2 type cytokines (15.47-49.89 %), proving that F3, N9, N6, and R10 were the key AAs of two epitopes. Mutants reduce allergic responses via the Th2 pathway. However, the roles of every key AA affecting allergenicity were different (P1-F3 > N9 and P2-N6 > R10). In addition, lower transport and higher efflux were observed in the mutants during transport absorption by Caco-2 cells. The allergenicity of HC was stronger when the transport absorption efficiency of epitopes and mutants was higher and their efflux was lower. Our study provides a novel method for revealing the allergenic molecular mechanisms of food allergens.

4.
iScience ; 27(6): 109931, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38974470

ABSTRACT

Large prospective studies are required to better elucidate the associations of physical activity, sedentary behaviors (SBs), and sleep with overall cancer and site-specific cancer risk, accounting for the interactions with genetic predisposition. The study included 360,271 individuals in UK Biobank. After a median follow-up of 12.52 years, we found higher total physical activity (TPA) level and higher sleep scores were related to reduced risk of cancer while higher SB level showed a positive association with cancer. Compared with high TPA-healthy sleep group and low SB-healthy sleep group, low TPA-poor sleep group and high SB-poor sleep group had the highest risk for overall cancer, breast cancer, and lung cancer. Adherence to a more active exercise pattern was associated with a lower risk of cancer irrespective of genetic risk. Our study suggests that improving the quality of sleep and developing physical activity habits might yield benefits in mitigating the cancer risk.

5.
MycoKeys ; 106: 287-301, 2024.
Article in English | MEDLINE | ID: mdl-38993356

ABSTRACT

Amphichorda has been previously accepted as a member of the Cordycipitaceae and currently it is considered a member of the Bionectriaceae. The substrates of Amphichorda were complex and varied, being mainly animal faeces. This study reports two new species of Amphichorda from Yunnan Province in south-western China. Based on the five-gene (nrSSU, nrLSU, tef-1α, rpb1 and rpb2) sequence and ITS data phylogenetic analysis, two new species, namely A.excrementa and A.kunmingensis, are proposed and a detailed description of the new species is provided. Amphichordaexcrementa and A.kunmingensis were isolated from animal faeces in the park. The morphological characteristics of two novel species and seven known species in Amphichorda are also compared.

6.
BMC Musculoskelet Disord ; 25(1): 530, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38987728

ABSTRACT

PURPOSE: Few studies have focused on the risk factors leading to postoperative blood transfusion after open reduction and internal fixation (ORIF) of proximal humeral fractures (PHFs) in the elderly. Therefore, we designed this study to explore potential risk factors of blood transfusion after ORIF for PHFs. We have also established a nomogram model to integrate and quantify our research results and give feedback. METHODS: In this study, we retrospectively analyzed the clinical data of elderly PHF patients undergoing ORIF from January 2020 to December 2021. We have established a multivariate regression model and nomograph. The prediction performance and consistency of the model were evaluated by the consistency coefficient and calibration curve, respectively. RESULTS: 162 patients met our inclusion criteria and were included in the final study. The following factors are related to the increased risk of transfusion after ORIF: time to surgery, fibrinogen levels, intraoperative blood loss, and surgical duration. CONCLUSIONS: Our patient-specific transfusion risk calculator uses a robust multivariable model to predict transfusion risk.The resulting nomogram can be used as a screening tool to identify patients with high transfusion risk and provide necessary interventions for these patients (such as preoperative red blood cell mobilization, intraoperative autologous blood transfusion, etc.).


Subject(s)
Blood Transfusion , Fracture Fixation, Internal , Nomograms , Open Fracture Reduction , Shoulder Fractures , Humans , Aged , Female , Male , Fracture Fixation, Internal/adverse effects , Fracture Fixation, Internal/methods , Retrospective Studies , Shoulder Fractures/surgery , Aged, 80 and over , Cross-Sectional Studies , Open Fracture Reduction/adverse effects , Open Fracture Reduction/methods , Risk Factors , Risk Assessment , Blood Loss, Surgical/prevention & control
7.
Alzheimers Dement ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958394

ABSTRACT

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors exhibit potential benefits in reducing dementia risk, yet the optimal beneficiary subgroups remain uncertain. METHODS: Individuals with type 2 diabetes (T2D) initiating either SGLT2 inhibitor or sulfonylurea were identified from OneFlorida+ Clinical Research Network (2016-2022). A doubly robust learning was deployed to estimate risk difference (RD) and 95% confidence interval (CI) of all-cause dementia. RESULTS: Among 35,458 individuals with T2D, 1.8% in the SGLT2 inhibitor group and 4.7% in the sulfonylurea group developed all-cause dementia over a 3.2-year follow-up, yielding a lower risk for SGLT2 inhibitors (RD, -2.5%; 95% CI, -3.0% to -2.1%). Hispanic ethnicity and chronic kidney disease were identified as the two important variables to define four subgroups in which RD ranged from -4.3% (-5.5 to -3.2) to -0.9% (-1.9 to 0.2). DISCUSSION: Compared to sulfonylureas, SGLT2 inhibitors were associated with a reduced risk of all-cause dementia, but the association varied among different subgroups. HIGHLIGHTS: New users of sodium-glucose cotransporter 2 (SGLT2) inhibitors were significantly associated with a lower risk of all-cause dementia as compared to those of sulfonylureas. The association varied among different subgroups defined by Hispanic ethnicity and chronic kidney disease. A significantly lower risk of Alzheimer's disease and vascular dementia was observed among new users of SGLT2 inhibitors compared to those of sulfonylureas.

8.
Clin Med Insights Case Rep ; 17: 11795476241262213, 2024.
Article in English | MEDLINE | ID: mdl-38895742

ABSTRACT

Background: Cerebral infarct associated with varicella-zoster virus (VZV) has been reported in the literature, while isolated central dizziness due to lateral medullary infarct (LMI) following VZV infection is rarely reported. Case report: We report the case of a 65-year-old man who presented to the neurology department because of herpes zoster on the right trigeminal nerve distribution. At 12 hours after admission, he developed transient vertigo along with nausea and unsteady walking and left-sided spontaneous horizontal nystagmus, gaze-evoked nystagmus, and upbeat nystagmus. The other usual signs of LMI including Horner syndrome, dysarthria, swallowing difficulty, and hemibody sensory change were absent. Video head impulse indicated decreased head impulse gain of the vestibulo-ocular reflex for the bilateral horizontal, anterior, and posterior semicircular canals with abnormal saccade waves. Suppression head impulse paradigm showed few downward saccades reflecting anti-compensatory saccades after the end of the head impulse back to the head-fixed target and decreased vestibulo-ocular reflex gain values of bilateral semicircular canals. Brain magnetic resonance imaging (MRI) showed a small infarct in the far dorsolateral portion of the left rostral medulla. The cerebrospinal fluid was positive for VZV DNA. Conclusions: In patients with VZV infection who develop dizziness, the possibility of cerebral infarct should be considered. Patients with facial herpes zoster and neurological symptoms always be screened for stroke using MRI and lumbar puncture should be performed and acyclovir administered empirically.

9.
Nutrients ; 16(11)2024 May 30.
Article in English | MEDLINE | ID: mdl-38892643

ABSTRACT

BACKGROUND: A gut-microbial metabolite, trimethylamine N-oxide (TMAO), has been associated with type 2 diabetes mellitus (T2DM). Few previous prospective studies have addressed associations between the changes in TMAO and T2DM incidence. METHODS: Data were derived from a longitudinal cohort conducted from 2019 to 2021 in rural areas of Fuxin County, Liaoning Province, China, and 1515 diabetes-free participants aged above 35 years were included. The concentrations of serum TMAO and its precursors were measured at two time points, namely in 2019 and 2021. TMAO and TMAO changes (ΔTMAO) were separately tested in a logistic regression model. For further examination, the odds ratios (ORs) for T2DM were calculated according to a combination of TMAO levels and ΔTMAO levels. RESULTS: During a median follow-up of 1.85 years, 81 incident cases of T2DM (5.35%) were identified. Baseline TMAO levels exhibited a nonlinear relationship, first decreasing and then increasing, and only at the highest quartile was it associated with the risk of T2DM. The OR for T2DM in the highest quartile of serum TMAO was 3.35 (95%CI: 1.55-7.26, p = 0.002), compared with the lowest quartile. As for its precursors, only choline level was associated with T2DM risk and the OR for T2DM in the Q3 and Q4 of serum choline was 3.37 (95%CI: 1.41-8.05, p = 0.006) and 4.72 (95%CI: 1.47-15.13, p = 0.009), respectively. When considering both baseline TMAO levels and ΔTMAO over time, participants with sustained high TMAO levels demonstrated a significantly increased risk of T2DM, with a multivariable-adjusted OR of 8.68 (95%CI: 1.97, 38.34). CONCLUSION: Both initial serum TMAO levels and long-term serum TMAO changes were collectively and significantly associated with the occurrence of subsequent T2DM events. Interventions aimed at normalizing TMAO levels, such as adopting a healthy dietary pattern, may be particularly beneficial in T2DM prevention.


Subject(s)
Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Methylamines , Humans , Diabetes Mellitus, Type 2/prevention & control , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/epidemiology , Methylamines/blood , Female , Male , Middle Aged , Longitudinal Studies , China/epidemiology , Adult , Risk Factors , Diet , Prospective Studies , Incidence , Aged , Choline/blood
10.
J Inflamm Res ; 17: 3515-3525, 2024.
Article in English | MEDLINE | ID: mdl-38836244

ABSTRACT

Objective: To evaluate the safety and feasibility of tonsillectomy and/or adenoidectomy (T&A) in pediatric patients with prolonged activated partial thromboplastin time (APTT) and coagulation factor deficiency. Methods: A prospective study was admitted to the children undergoing T&A at our institution between October 2019 and January 2020, specifically focusing on preoperative coagulation function. Within this group, we identified 5 patients exhibiting prolonged APTT and coagulation factor deficiencies, constituting the experimental group, and 10 patients matched by gender and age with normal blood coagulation function were selected as the control group. Comparative analyses between the two groups were conducted, focusing on surgical duration, intraoperative bleeding volume, duration of hospital stay, and postoperative complications such as active bleeding across the groups. At the six-month postoperative mark, a reassessment of coagulation functions and factor assays was conducted within the experimental group. Results: No statistically significant differences were discovered in terms of surgical duration or bleeding volume when comparing the experimental subgroups with their respective control counterparts. Furthermore, there were no incidences of postoperative active bleeding observed in any of the groups. Notably, postoperative APTT values (32.7 ± 1.7s) exhibited a significant disparity compared to preoperative levels (43.7 ± 1.8s, p < 0.01). Coagulation factors demonstrated normalization, evidenced by a significant difference in postoperative Factor XII levels (40.2 ± 5.4%) compared to preoperative levels (63.1 ± 5.9%, p < 0.01). Conclusion: Prolonged APTT with FXII factor deficiency does not show a significant bleeding tendency and is not a contraindication for T&A surgery. Post T&A surgery, children with abnormal coagulation function and deficient clotting factors show significant improvement compared to pre-surgery. It is important to consider that chronic inflammation in adenoids and tonsils may contribute to the prolongation of APTT and the manifestation of Factor XII deficiency.

11.
Front Immunol ; 15: 1374390, 2024.
Article in English | MEDLINE | ID: mdl-38868768

ABSTRACT

Immunotherapy for hematological malignancies is a rapidly advancing field that has gained momentum in recent years, primarily encompassing chimeric antigen receptor T-cell (CAR-T) therapies, immune checkpoint inhibitors, and other modalities. However, its clinical efficacy remains limited, and drug resistance poses a significant challenge. Therefore, novel immunotherapeutic targets and agents need to be identified. Recently, N6-methyladenosine (m6A), the most prevalent RNA epitope modification, has emerged as a pivotal factor in various malignancies. Reportedly, m6A mutations influence the immunological microenvironment of hematological malignancies, leading to immune evasion and compromising the anti-tumor immune response in hematological malignancies. In this review, we comprehensively summarize the roles of the currently identified m6A modifications in various hematological malignancies, with a particular focus on their impact on the immune microenvironment. Additionally, we provide an overview of the research progress made in developing m6A-targeted drugs for hematological tumor therapy, to offer novel clinical insights.


Subject(s)
Adenosine , Hematologic Neoplasms , Tumor Microenvironment , Humans , Tumor Microenvironment/immunology , Hematologic Neoplasms/immunology , Hematologic Neoplasms/therapy , Adenosine/analogs & derivatives , Adenosine/immunology , Adenosine/metabolism , Animals , Immunotherapy/methods
12.
Neurology ; 103(2): e209502, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-38875513

ABSTRACT

BACKGROUND AND OBJECTIVES: The Patient-Ranked Order of Function (PROOF) is a novel approach to account for patient-reported preferences in the evaluation of treatments of amyotrophic lateral sclerosis (ALS). In this study, we assess the reliability and prognostic value of different sets of patient-reported preferences that can be used for the PROOF end point. METHODS: Data were obtained through online surveys over the course of 12 months using the population-based registry of the Netherlands. Patients were asked to score functional domains of the ALS Functional Rating Scale (ALSFRS-R) and rank the order of importance of each domain. Two weeks after the initial invite, the questionnaire was repeated to evaluate test-retest reliability. Vital status was extracted from the municipal population register. RESULTS: In total, 611 patients with ALS were followed up for survival and 382 patients were included in the test-retest reliability study. All versions of PROOF, using different sets of preferences, resulted in excellent reliability (intraclass correlation coefficients ranged from 0.89 [95% CI 0.87-0.91] to 0.97 [95% CI 0.97-0.98], all p < 0.001), without systematic differences between baseline and week 2 (mean rank difference range -1 to -3 [95% CI range -8 to 2], all p > 0.20). Preferences about future events were more variable than preferences about current symptoms. All versions of PROOF strongly predicted overall survival (hazard ratios per 10th rank percentile ranged from 0.80 to 0.83 [95% CI range 0.76-0.87], all p < 0.001) and had a more even separation of survival curves between rank-stratified subgroups compared with the ALSFRS-R total score. DISCUSSION: In a large cohort of patients, we show how patient-reported preferences can be measured and integrated reliably with the ALSFRS-R without leading to systematic bias. Patient preferences may provide unique prognostic information in addition to what is already measured conventionally. This could provide a more comprehensive understanding of how medical interventions effectively address the patient's concerns and improve what matters most to them.


Subject(s)
Amyotrophic Lateral Sclerosis , Patient Preference , Humans , Amyotrophic Lateral Sclerosis/therapy , Amyotrophic Lateral Sclerosis/diagnosis , Amyotrophic Lateral Sclerosis/physiopathology , Male , Female , Middle Aged , Reproducibility of Results , Prognosis , Aged , Netherlands , Clinical Trials as Topic , Surveys and Questionnaires , Registries
13.
J Phys Chem C Nanomater Interfaces ; 128(24): 10084-10107, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38919725

ABSTRACT

All-inorganic metal halide perovskite nanocrystals (PeNCs) show great potential for the next generation of perovskite light-emitting diodes (PeLEDs). However, trap-assisted recombination negatively impacts the optoelectronic properties of PeNCs and prevents their widespread adoption for commercial exploitation. To mitigate trap-assisted recombination and further enhance the external quantum efficiency of PeLEDs, A/B-site doping has been widely investigated to tune the bandgap of PeNCs. The bandgap of PeNCs is adjustable within a small range (no more than 0.1 eV) by A-site cation doping, resulting in changes in the bond length of Pb-X and the angle of [PbX6]4. Nevertheless, B-site doping of PeNCs has a more significant impact on the bandgap level through modification of surface defect states. In this perspective, we delve into the synthesis of PeNCs with A/B-site doping and their impacts on the structural and optoelectronic properties, as well as their impacts on the performance of subsequent PeLEDs. Furthermore, we explore the A-site and B-site doping mechanisms and the impact of device architecture on doped PeNCs to maximize the performance and stability of PeLEDs. This work presents a comprehensive overview of the studies on A-site and B-site doping in PeNCs and approaches to unlock their full potential in the next generation of LEDs.

14.
Sci Data ; 11(1): 629, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877023

ABSTRACT

The Chungtien schizothoracin (Ptychobarbus chungtienensis), an endangered fish species endemic to the Zhongdian Plateau, remains underexplored in terms of transcriptomic sequencing. This investigation used tissues from five distinct organs (heart, liver, spleen, kidney, and brain) of the Chungtien schizothoracin for PacBio Iso-seq and RNA-seq analyses, yielding a repertoire of 16,598 full-length transcripts spanning lengths from 363 bp to 7,157 bp. Gene family clustering and phylogenetic analysis encompassed a comprehensive set of 13 fish species, all of which were cyprinids, including the zebrafish and the examined species Ptychobarbus chungtienensis. Moreover, the identification of long non-coding RNAs (lncRNAs) and coding sequences was accomplished across all five tissues. Comprehensive analyses of gene expression profiles and differentially expressed genes among the above five tissues were performed. In summary, the obtained full-length transcripts and detailed gene expression profiles of the Chungtien schizothoracin tissues furnish crucial expression data and genetic sequences, laying the groundwork for future investigations and fostering a holistic comprehension of the adaptive mechanisms inherent in the Chungtien schizothoracin under various conditions.


Subject(s)
Cyprinidae , Phylogeny , Transcriptome , Animals , Cyprinidae/genetics , RNA-Seq , RNA, Long Noncoding/genetics , Endangered Species
15.
Bioorg Chem ; 149: 107500, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38823310

ABSTRACT

This study aimed to develop the first dual-target small molecule inhibitor concurrently targeting Discoidin domain receptor 1 (DDR1) and Epidermal growth factor receptor (EGFR), which play a crucial interdependent roles in non-small cell lung cancer (NSCLC), demonstrating a synergistic inhibitory effect. A series of innovative dual-target inhibitors for DDR1 and EGFR were discovered. These compounds were designed and synthesized using structural optimization strategies based on the lead compound BZF02, employing 4,6-pyrimidine diamine as the core scaffold, followed by an investigation of their biological activities. Among these compounds, D06 was selected and showed micromolar enzymatic potencies against DDR1 and EGFR. Subsequently, compound D06 was observed to inhibit NSCLC cell proliferation and invasion. Demonstrating acceptable pharmacokinetic performance, compound D06 exhibited its anti-tumor activity in NSCLC PC-9/GR xenograft models without apparent toxicity or significant weight loss. These collective results showcase the successful synthesis of a potent dual-targeted inhibitor, suggesting the potential therapeutic efficacy of co-targeting DDR1 and EGFR for DDR1/EGFR-positive NSCLC.


Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Cell Proliferation , Discoidin Domain Receptor 1 , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , ErbB Receptors , Lung Neoplasms , Protein Kinase Inhibitors , Humans , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/metabolism , Discoidin Domain Receptor 1/antagonists & inhibitors , Discoidin Domain Receptor 1/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Cell Proliferation/drug effects , Structure-Activity Relationship , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/chemical synthesis , Animals , Molecular Structure , Mice , Drug Discovery , Mice, Nude , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/pathology , Neoplasms, Experimental/metabolism , Cell Line, Tumor , Mice, Inbred BALB C
16.
J Environ Manage ; 365: 121535, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38917542

ABSTRACT

Groundwater heat pump (GWHP) systems are increasingly popular as low-carbon and environmentally friendly technologies, but well clogging induced by iron remains a significant issue. This study investigated the clogging characteristics and biogeochemistry of three typical wells (pumping, injection, and observation wells) in an operating GWHP system using video imaging, sampling, and analysis of hydrogeochemical and microbial data. The results revealed that iron-induced well clogging is a complex process involving physical, chemical, and microbial factors. Pumping wells experience clogging due to water mixing with varying redox conditions, resulting in hematite-based iron oxide deposits. Injection wells exhibit higher clogging severity, with transformed oxidation and accumulation of reduced iron minerals at the solid-liquid interface, resulting in darker colored clogs with magnetite. Clogging in both extraction and injection wells is closely related to iron-rich aquifer sections, where severe clogging occurs. Shallow clogging due to iron oxide is limited and attributed to the oxidation of zero-valent iron in well casing material. Iron-oxidizing bacteria and iron-reducing bacteria were detected in the consolidated deposits of clogged wells, indicating their involvement in the clogging formation process. Moreover, a strong correlation was observed between the presence of nitrate-reducing bacteria in the water phase and the severity of clogging, suggesting a possible link between iron oxidation and nitrate reduction in the system. Geochemical modeling results further supported the observed clogging severity in GWHP systems and confirmed varying clogging mechanisms in different wells and depths. These findings contribute to the understanding of clogging in GWHP operations, aiding in robust water utilization and energy-saving efforts, and supporting global carbon reduction initiatives.

17.
Chin J Integr Med ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38910189

ABSTRACT

OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (CT) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS: Patients with a nadir CT value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.

18.
Front Immunol ; 15: 1309447, 2024.
Article in English | MEDLINE | ID: mdl-38855105

ABSTRACT

Introduction: Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), presents significant challenges in patient management and treatment outcomes. The identification of novel LN-related biomarkers and therapeutic targets is critical to enhancing treatment outcomes and prognosis for patients. Methods: In this study, we analyzed single-cell expression data from LN (n=21) and healthy controls (n=3). A total of 143 differentially expressed genes were identified between the LN and control groups. Then, proteomics analysis of LN patients (n=9) and control (SLE patients without LN, n=11) revealed 55 differentially expressed genes among patients with LN and control group. We further utilizes protein-protein interaction network and functional enrichment analyses to elucidate the pivotal role of COL6A3 in key signaling pathways. Its diagnostic value is evaluate through its correlation with disease progression and renal function metrics, as well as Receiver Operating Characteristic Curve (ROC) analysis. Additionally, immunohistochemistry and qPCR experiments were performed to validate the expression of COL6A3 in LN. Results: By comparison of single-cell and proteomics data, we discovered that COL6A3 is significantly upregulated, highlighting it as a critical biomarker of LN. Our findings emphasize the substantial involvement of COL6A3 in the pathogenesis of LN, particularly noting its expression in mesangial cells. Through comprehensive protein-protein interaction network and functional enrichment analyses, we uncovered the pivotal role of COL6A3 in key signaling pathways including integrin-mediated signaling pathways, collagen-activated signaling pathways, and ECM-receptor interaction, suggesting potential therapeutic targets. The diagnostic utility is confirmed by its correlation with disease progression and renal function metrics of the glomerular filtration rate. ROC analysis further validates the diagnostic value of COL6A3, with the area under the ROC values of 0.879 in the in-house cohort, and 0.802 and 0.915 in tubular and glomerular external cohort samples, respectively. Furthermore, immunohistochemistry and qPCR experiments were consistent with those obtained from the single-cell RNA sequencing and proteomics studies. Discussion: These results proved that COL6A3 is a promising biomarker and therapeutic target, advancing personalized medicine strategies for LN.


Subject(s)
Biomarkers , Collagen Type VI , Lupus Nephritis , Proteomics , Single-Cell Analysis , Humans , Lupus Nephritis/genetics , Lupus Nephritis/metabolism , Collagen Type VI/genetics , Collagen Type VI/metabolism , Proteomics/methods , Female , Adult , Male , Transcriptome , Protein Interaction Maps , Gene Expression Profiling
19.
Nat Chem ; 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918581

ABSTRACT

Providing affordable, safe drinking water and universal sanitation poses a grand societal challenge. Here we developed atomically dispersed Au on potassium-incorporated polymeric carbon nitride material that could simultaneously boost photocatalytic generation of ·OH and H2O2 with an apparent quantum efficiency over 85% at 420 nm. Potassium introduction into the poly(heptazine imide) matrix formed strong K-N bonds and rendered Au with an oxidation number close to 0. Extensive experimental characterization and computational simulations revealed that the low-valent Au altered the materials' band structure to trap highly localized holes produced under photoexcitation. These highly localized holes could boost the 1e- water oxidation reaction to form highly oxidative ·OH and simultaneously dissociate the hydrogen atom in H2O, which greatly promoted the reduction of oxygen to H2O2. The photogenerated ·OH led to an efficiency enhancement for visible-light-response superhydrophilicity. Furthermore, photo-illumination in an onsite fixed-bed reactor could disinfect water at a rate of 66 L H2O m-2 per day.

20.
Brain Behav Immun ; 120: 413-429, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38925413

ABSTRACT

Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by involuntary movements, cognitive deficits, and psychiatric symptoms. Currently, there is no cure, and only limited treatments are available to manage the symptoms and to slow down the disease's progression. The molecular and cellular mechanisms of HD's pathogenesis are complex, involving immune cell activation, altered protein turnover, and disturbance in brain energy homeostasis. Microglia have been known to play a dual role in HD, contributing to neurodegeneration through inflammation but also enacting neuroprotective effects by clearing mHTT aggregates. However, little is known about the contribution of microglial metabolism to HD progression. This study explores the impact of a microglial metabolite transporter, equilibrative nucleoside transporter 3 (ENT3), in HD. Known as a lysosomal membrane transporter protein, ENT3 is highly enriched in microglia, with its expression correlated with HD severity. Using the R6/2 ENT3-/- mouse model, we found that the deletion of ENT3 increases microglia numbers yet worsens HD progression, leading to mHTT accumulation, cell death, and disturbed energy metabolism. These results suggest that the delicate balance between microglial metabolism and function is crucial for maintaining brain homeostasis and that ENT3 has a protective role in ameliorating neurodegenerative processes.

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