Deciphering biomolecular complexities: the indispensable role of surface-enhanced Raman spectroscopy in modern bioanalytical research.

Surface-enhanced Raman spectroscopy (SERS) has emerged as an indispensable analytical tool in biomolecular research, providing unmatched sensitivity critical for the elucidation of biomolecular structures. This review presents a thorough examination of SERS, outlining its fundamental principles, cataloging its varied applications within the biomolecular sphere, and contemplating its future developmental trajectories. We begin with a detailed analysis of SERS's mechanistic principles, emphasizing both the phenomena of surface enhancement and the complexities inherent in Raman scattering spectroscopy. Subsequently, we delve into the pivotal role of SERS in the structural analysis of diverse biomolecules, including proteins, nucleic acids, lipids, carbohydrates, and biochromes. The remarkable capabilities of SERS extend beyond mere detection, offering profound insights into biomolecular configurations and interactions, thereby enriching our comprehension of intricate biological processes. This review also sheds light on the application of SERS in real-time monitoring of various bio-relevant compounds, from enzymes and coenzymes to metal ion-chelate complexes and cellular organelles, thereby providing a holistic view and empowering researchers to unravel the complexities of biological systems. We also address the current challenges faced by SERS, such as enhancing sensitivity and resolution, developing stable and reproducible substrates, and conducting thorough analyses in complex biological matrices. Nonetheless, the continual advancements in nanotechnology and spectroscopy solidify the standing of SERS as a formidable force in biomolecular research. In conclusion, the versatility and robustness of SERS not only deepen our understanding of biomolecular intricacies but also pave the way for significant developments in medical research, therapeutic innovation, and diagnostic approaches.

Phthalates Boost Natural Transformation of Extracellular Antibiotic Resistance Genes through Enhancing Bacterial Motility and DNA Environmental Persistence.

The environmental dissemination of extracellular antibiotic resistance genes (eARGs) in wastewater and natural water bodies has aroused growing ecological concerns. The coexisting chemical pollutants in water are known to markedly affect the eARGs transfer behaviors of the environmental microbial community, but the detailed interactions and specific impacts remain elusive so far. Here, we revealed a concentration-dependent impact of dimethyl phthalate (DMP) and several other types of phthalate esters (common water pollutants released from plastics) on the natural transformation of eARGs. The DMP exposure at an environmentally relevant concentration (10 µg/L) resulted in a 4.8-times raised transformation frequency of Acinetobacter baylyi but severely suppressed the transformation at a high concentration (1000 µg/L). The promotion by low-concentration DMP was attributed to multiple mechanisms, including increased bacterial mobility and membrane permeability to facilitate eARGs uptake and improved resistance of the DMP-bounded eARGs (via noncovalent interaction) to enzymatic degradation (with suppressed DNase activity). Similar promoting effects of DMP on the eARGs transformation were also found in real wastewater and biofilm systems. In contrast, higher-concentration DMP suppressed the eARGs transformation by disrupting the DNA structure. Our findings highlight a potentially underestimated eARGs spreading in aquatic environments due to the impacts of coexisting chemical pollutants and deepen our understanding of the risks of biological-chemical combined pollution in wastewater and environmental water bodies.

Association between alcohol consumption and peripheral artery disease: Two de novo prospective cohorts and a systematic review with meta-analysis.

AIMS: The association between alcohol consumption and risk of peripheral artery disease (PAD) is inconclusive. We conducted this study to examine the association between alcohol consumption and PAD risk in two de novo cohort studies and a meta-analysis of observational studies. METHODS AND RESULTS: A systematic review was conducted to identify studies on alcohol consumption in relation to PAD risk. We further used data from two cohorts of 70,116 Swedish and 405,406 British adults and performed a meta-analysis of results from previously published studies and current cohort studies. There was a U-shaped association between alcohol consumption and incident PAD risk in the Swedish and British cohorts. The meta-analysis of results of these two cohorts and previously published studies found that compared with non- or never-drinkers, the relative risk of PAD was 0.83 (95% confidence interval [CI] 0.77-0.89), 0.81 (95% CI 0.74-0.90), and 0.94 (95% CI 0.83-1.07) for light, moderate, and high-to-heavy alcohol drinkers, respectively. The nonlinear meta-analysis revealed a possibly U-shaped association between alcohol consumption and PAD risk (P-nonlinearity <0.001). The risk of PAD was observed to be the lowest for 2 drinks/week and to be pronounced for ≥10 drinks/week. All these associations persisted in a sensitivity meta-analysis including cohort and other type of observational studies. CONCLUSION: Alcohol intake ≤ 2 drinks/week was associated with a reduced risk of PAD and the risk of PAD became pronounced with intake ≥10 drinkers/week.

The association between alcohol consumption and the risk of peripheral artery disease is conflicting between studies and thus remains undetermined. In the two de novo cohort analyses, we found a U-shaped association between alcohol consumption and peripheral artery disease risk in the Swedish and British populations. In the meta-analysis, light-to-moderate consumption of alcohol was associated with a reduced risk of peripheral artery disease. The dose-response meta-analysis showed that the risk of peripheral artery disease became pronounced for alcohol consumption ≥10 drinkers/week. This is an observational study that cannot infer causality between alcohol consumption and peripheral artery disease risk. We are not able to assess the specific associations to different types of alcoholic beverages.

Yiqi Kaimi prescription regulates protein phosphorylation to promote intestinal motility in slow transit constipation.

ETHNOPHARMACOLOGICAL RELEVANCE: The clinical efficacy of the Yiqi Kaimi prescription has been confirmed in slow transit constipation. However, the effects and biological mechanism of Yiqi Kaimi prescription are still unclear. AIMS OF THE STUDY: To identify the effects of Yiqi Kaimi prescription on intestinal motility; To reveal the potential key targets and pathways of Yiqi Kaimi prescription for the treatment of slow transit constipation. MATERIALS AND METHODS: The effects of Yiqi Kaimi prescription on slow transit constipation were investigated in a mouse model. The terminal ink propulsion experiment and fecal indocyanine green imaging was used to measure the intestinal transit time. Protein phosphorylation changes in colon tissues treated with Yiqi Kaimi prescription were detected using a Phospho Explorer antibody microarray. Bioinformatic analyses were performed using the Database for Annotation Visualization and Integrated Discovery (DAVID) and the Search Tool for the Retrieval of Interacting Genes (STRING). Western blot analysis and immunohistochemistry confirmed the observed changes in phosphorylation. RESULT: s: Yiqi Kaimi prescription significantly increased the intestinal transit rate (P < 0.05 vs. model) and reduced the time to first discharge of feces containing fecal indocyanine green imaging in mice (P < 0.05 vs. model). The administration of Yiqi Kaimi prescription induced phosphorylation changes in 41 proteins, with 9 upregulated proteins and 32 downregulated proteins. Functional classification of the phosphorylated proteins with DAVID revealed that the critical biological processes included tyrosine protein kinases, positive regulation of calcium-mediated signaling and response to muscle stretch. The phosphorylation of the spleen tyrosine kinase (SYK) at Tyr348 increased 2.19-fold, which was the most significant change. The phosphorylation level of the transcription factor p65 (RELA) at Thr505 was decreased 0.57-fold. SYK was a hub protein in the protein-protein interaction network and SYK and RELA formed the core of the secondary subnetwork. The key protein phosphorylation after treatment with Yiqi Kaimi prescription were verified by Western blot analysis and immunohistochemistry. CONCLUSION: Yiqi Kaimi prescription significantly enhanced intestinal motility. This effect was attributed to alterations in the phosphorylation levels of various target proteins. The observed changes in protein phosphorylation, including SYK and RELA, may serve as crucial factors in the treatment of slow transit constipation.

[Research progress on active ingredients of Coicis Semen].

As a common medicinal and edible resource in China, Coicis Semen has a long history of cultivation and medicinal use. Traditional Chinese medicine(TCM) clinically believes that Coicis Semen has the effect of strengthening the spleen and tonifying the lungs, clearing heat and dampness, removing pus and paralysis, and stopping diarrhea. Therefore, it is used to treat edema, foot odor, spleen deficiency, diarrhea, and other symptoms. The above effects are closely related to the active ingredients of Coicis Semen, such as esters, fatty acids, polysaccharides, proteins, as well as phenolic acids, sterols, flavonoids, lactams, triterpenes, alkaloids, and adenosine. Modern research has found that Coicis Semen also has anti-cancer, anti-inflammatory, antioxidant, hypoglycemic, and hypotensive effects and other pharmacological activities, and it can improve immunity and regulate lipid metabolism. Coicis Semen is widely distributed in China, mainly produced in Guizhou, Yunnan, Fujian, Sichuan, and other places, and the quality of Coicis Semen from different origins varies. From ancient times to the present, Coicis Semen processing methods have experienced the process from simple to complex, and the types of auxiliary materials are more extensive, such as soil, bran, and river sand. These processing methods have been inherited from generation to generation. Nowadays, the commonly used methods are bran-fried, stir-fried, sand-fried, etc. In this paper, by reviewing the relevant literature in China and abroad in recent years, the main active ingredients and related pharmacological effects of Coicis Semen are sorted out, and the effects of different origins and processing methods on the chemical composition of Coicis Semen are summarized, with a view to providing references for the comprehensive development and utilization of Coicis Semen and the further study of its mechanism of action.

Interfacial Modulation of Spin-Orbit Torques Induced by Two-Dimensional van der Waals Material ZrSe3.

Two-dimensional van der Waals (2D vdW) materials are widely used in spin-orbit torque (SOT) devices. Recent studies have demonstrated the low crystal symmetry and large spin Hall conductivity of 2D vdW ZrSe3, indicating its potential applications in low-power SOT devices. Here, we study the interfacial contribution of SOTs and current-induced magnetization switching in the ZrSe3/Py (Ni80Fe20) and ZrSe3/Cu/Py heterostructures. SOT efficiencies of samples are detected by the spin-torque ferromagnetic resonance (ST-FMR), and out-of-plane damping-like torque (τB) is observed. The ratio between τB and the field-like torque (τA) decreases from 0.175 to 0.138 when inserting 1 nm Cu at the interface and then drops to 0.001 when the thickness of Cu intercalation is 2 nm, indicating that Cu intercalation inhibits the τB component of SOT. Moreover, the SOT efficiency is increased from 3.05 to 5.21, which may be attributed to the Cu intercalation being beneficial to improve the interface between Py and ZrSe3. Theoretical calculation has shown that the Cu spacer can change the conductivity of ZrSe3 from semiconductor to conductor, thereby decreasing the Schottky barrier and increasing the transmission efficiency of the spin current. Furthermore, magneto-optical Kerr effect (MOKE) microscopy is employed to verify the current-driven magnetization switching in these structures. In comparison to the ZrSe3/Py bilayer, the critical current density of ZrSe3/Cu/Py is reduced when inserting 1 nm Cu, demonstrating the higher SOT efficiency and lower power consumption in ZrSe3/Cu/Py structures.

Bedaquiline susceptibility testing of Mycobacterium abscessus complex and Mycobacterium avium complex: a meta-analysis study.

OBJECTIVE: This study aims to estimate the overall in vitro activity of bedaquiline (BDQ) against clinical isolates of Mycobacterium abscessus complex (MABS) and Mycobacterium avium complex (MAC), considering BDQ as a repurposed drug for non-tuberculous mycobacteria (NTM) infections. METHODS: We conducted a systematic review of publications in PubMed/ MEDLINE, Web of Science, and Embase up to April 15, 2023. Studies were included if they followed the Clinical and Laboratory Standards Institute (CLSI) criteria for drug susceptibility testing (DST). Using a random effects model, we assessed the overall in vitro BDQ resistance rate in clinical isolates of MABS and MAC. Sources of heterogeneity were analyzed using Cochran's Q and the I2 statistic. All analyses were performed using CMA V3.0. RESULTS: A total of 24 publications (19 reports for MABS and 11 for MAC) were included. Using 1 µg/mL and 2 µg/mL as the breakpoint for BDQ resistance, the pooled rates of in vitro BDQ resistance in clinical isolates of MABS were found to be 1.8% (95% confidence interval [CI], 0.7-4.6%) and 1.7% (95% CI, 0.6-4.4%), respectively. In the case of MAC, the pooled rates were 1.7% (95% CI, 0.4-6.9%) and 1.6% (95% CI, 0.4-6.8%) for 1 µg/mL and 2 µg/mL, respectively. CONCLUSION: This study reports the prevalence of BDQ resistance in clinical isolates of MABS and MAC. The findings suggest that BDQ holds potential as a repurposed drug for treating MABS and MAC infections.

CRL4DCAF4 E3 ligase-mediated degradation of MEN1 transcriptionally reactivates hTERT to sustain immortalization in colorectal cancer cells.

Telomerase reactivation is implicated in approximately 85% of human cancers, yet its underlying mechanism remains elusive. In this study, we elucidate that the Cullin RING Ubiquitin Ligase 4 (CRL4) complex drives the reactivation of human telomerase reverse transcriptase (hTERT) in colorectal cancer (CRC) by degrading the tumor suppressor, menin 1 (MEN1). Our data show that, in noncancerous intestinal epithelial cells, the transcription factor specificity protein 1 (Sp1) recruits both the histone acetyltransferase p300 and MEN1 to suppress hTERT expression, thus maintaining telomere shortness post-cell division. Inflammation-induced microenvironments trigger an activation of the CRL4DCAF4 E3 ligase, leading to MEN1 ubiquitination and degradation in CRC cells. This process nullifies MEN1's inhibitory action, reactivates hTERT expression at the transcriptional level, interrupts telomere shortening, and spurs uncontrolled cellular proliferation. Notably, MEN1 overexpression in CRC cells partially counteracts these oncogenic phenotypes. NSC1517, an inhibitor of the CRL4DCAF4 complex identified through high-throughput screening from a plant-derived chemical pool, hinders MEN1 degradation, attenuates hTERT expression, and suppresses tumor growth in mouse xenograft models. Collectively, our research elucidates the transcriptional mechanism driving hTERT reactivation in CRC. Targeting the CRL4DCAF4 E3 ligase emerges as a promising strategy to counteract cancer cell immortalization and curb tumor progression.

CYP3A5 unexpectedly regulates glucose metabolism through the AKT-TXNIP-GLUT1 axis in pancreatic cancer.

CYP3A5 is a cytochrome P450 (CYP) enzyme that metabolizes drugs and contributes to drug resistance in cancer. However, it remains unclear whether CYP3A5 directly influences cancer progression. In this report, we demonstrate that CYP3A5 regulates glucose metabolism in pancreatic ductal adenocarcinoma. Multi-omics analysis showed that CYP3A5 knockdown results in a decrease in various glucose-related metabolites through its effect on glucose transport. A mechanistic study revealed that CYP3A5 enriches the glucose transporter GLUT1 at the plasma membrane by restricting the translation of TXNIP, a negative regulator of GLUT1. Notably, CYP3A5-generated reactive oxygen species were proved to be responsible for attenuating the AKT-4EBP1-TXNIP signaling pathway. CYP3A5 contributes to cell migration by maintaining high glucose uptake in pancreatic cancer. Taken together, our results, for the first time, reveal a role of CYP3A5 in glucose metabolism in pancreatic ductal adenocarcinoma and identify a novel mechanism that is a potential therapeutic target.

miR-2940-1 is involved in the circadian regulation of oviposition in Aedes albopictus.

The vast majority of all global species have circadian rhythm cycles that allow them to adapt to natural environments. These regular rhythms are regulated by core clock genes and recent studies have also implicated roles for microRNAs in this regulation. Oviposition is an important circadian behavior in the reproductive cycle of insect vectors of diseases, and little is known about the rhythm or its regulation in mosquitoes. Aedes albopictus is a diurnal mosquito that transmits arboviruses and is the major cause of outbreaks of dengue fever in China. We analyzed the oviposition rhythm patterns of A. albopictus under different light/dark conditions and show that the mosquitoes have an oviposition peak between zeitgeber time 9 (ZT 9) and ZT 12. Furthermore, the antagomir-mediated knockdown of expression of the microRNA miR-2940-1 affected the oviposition rhythm of A. albopictus. These data support the conclusion that miR-2940-1 is involved in the regulation of oviposition rhythm in A. albopictus and provide a foundation for using oviposition rhythms as a new target for vector mosquito control.

Mutation breeding of high-stress resistant strains for succinic acid production from corn straw.

The production of succinic acid from corn stover is a promising and sustainable route; however, during the pretreatment stage, byproducts such as organic acids, furan-based compounds, and phenolic compounds generated from corn stover inhibit the microbial fermentation process. Selecting strains that are resistant to stress and utilizing nondetoxified corn stover hydrolysate as a feedstock for succinic acid production could be effective. In this study, A. succinogenes CICC11014 was selected as the original strain, and the stress-resistant strain A. succinogenes M4 was obtained by atmospheric and room temperature plasma (ARTP) mutagenesis and further screening. Compared to the original strain, A. succinogenes M4 exhibited a twofold increase in stress resistance and a 113% increase in succinic acid production when hydrolysate was used as the substrate. By conducting whole-genome resequencing of A. succinogenes M4 and comparing it with the original strain, four nonsynonymous gene mutations and two upstream regions with base losses were identified. KEY POINTS: • A high-stress-resistant strain A. succinogenes M4 was obtained by ARTP mutation •  The production of succinic acid increased by 113% • The mutated genes of A. succinogenes M4 were detected and analyzed.

Analysis of O-acetylated sialic acids by 3-nitrophenylhydrazine derivatization combined with LC-MS/MS.

Sialic acids are a family of monosaccharides that share a nine-carbon backbone and a carboxyl group. A recent derivatization method based on 3-nitrophenylhydrazine (3-NPH) provides a mild chemical labeling technique for biomolecules containing carbonyl or carboxyl groups. In this study, we utilized 3-NPH to label sialic acids via a two-step derivatization process. The derivatized species can produce a common reporter ion corresponding to C1-C3 with two labels, and a fragment differentiating between Neu5Ac, Neu5Gc, and KDN. This method is compatible with O-acetylated sialic acids and provides high sensitivity to Neu5Gc and KDN, and since the utilization of dual labeling significantly enhances the hydrophobicity of derivatives, it can effectively mitigate matrix effects when combined with parallel reaction monitoring technology. Negative-ion tandem mass spectrometry (MS/MS) analysis reveals a distinctive fragmentation profile for the 4-O-acetylated species, while the other sialic acids yield similar MS/MS spectra with a high abundance of reporter ions. Using the reporter ion as a transition, this analytical strategy is effective for analyzing complex biological samples. For example, it was successfully employed to quantify sialic acids in the intestinal tissues of several carp species, demonstrating its potential in sialylation research.

Inferior parietal cortex represents relational structures for explicit transitive inference.

The human brain is distinguished by its ability to perform explicit logical reasoning like transitive inference. This study investigated the functional role of the inferior parietal cortex in transitive inference with functional MRI. Participants viewed premises describing abstract relations among items. They accurately recalled the relationship between old pairs of items, effectively inferred the relationship between new pairs of items, and discriminated between true and false relationships for new pairs. First, the inferior parietal cortex, but not the hippocampus or lateral prefrontal cortex, was associated with transitive inference. The inferior parietal activity and functional connectivity were modulated by inference (new versus old pairs) and discrimination (true versus false pairs). Moreover, the new/old and true/false pairs were decodable from the inferior parietal representation. Second, the inferior parietal cortex represented an integrated relational structure (ordered and directed series). The inferior parietal activity was modulated by serial position (larger end versus center pairs). The inferior parietal representation was modulated by symbolic distance (adjacent versus distant pairs) and direction (preceding versus following pairs). It suggests that the inferior parietal cortex may flexibly integrate observed relations into a relational structure and use the relational structure to infer unobserved relations and discriminate between true and false relations.

Socioeconomic disparities in the association of age at first live birth with incident stroke among Chinese parous women: A prospective cohort study.

Background: Stroke has become a significant public health issue in China. Although studies have shown that women's age at first live birth (AFLB) might be associated with incident stroke, there is limited evidence on this relationship among Chinese parous women. Likewise, the nature of this association across urban-rural socioeconomic status (SES) has yet to be explored. In this prospective study, we sought to investigate the associations of women's AFLB with the risk of incident stroke and its subtypes (ischaemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage) and to explore the differences of these associations as well as the population-level impacts across SES classes. Methods: We used data on 290 932 Chinese parous women from the China Kadoorie Biobank who were recruited in the baseline survey between 2004 and 2008 and followed up until 2015. We used latent class analysis to identify urban-rural SES classes and Cox proportional hazard regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for AFLB's association with incident stroke. We then calculated population attributable fraction (PAF) to demonstrate the population-level impact of later AFLB on stroke. Results: Around 8.9% of parous women developed stroke after AFLB. Compared with women with AFLB <22 years, those with older AFLB had a higher risk of total stroke, with fully adjusted HRs (95% CI) of 1.71 (95% CI = 1.65-1.77) for 22-24 years and 3.37 (95% CI = 3.24-3.51) for ≥25 years. The associations of AFLB with ischaemic stroke were stronger among rural-low-SES participants. We found the highest PAFs of ischaemic stroke (60.1%; 95% CI = 46.2-70.3) associated with later AFLB for urban-high-SES individuals. Conclusions: Older AFLB was associated with higher risks of incident stroke and its subtypes among Chinese parous women, with stronger associations between AFLB and ischaemic stroke among rural-low-SES participants. Targeted medical advice for pregnant women of different ages could have long-term benefits for stroke prevention.

CDC45 promotes the stemness and metastasis in lung adenocarcinoma by affecting the cell cycle.

OBJECTIVE: This study aimed to assess the functions of cell division cycle protein 45 (CDC45) in Non-small cell lung cancer (NSCLC) cancer and its effects on stemness and metastasis. METHODS: Firstly, differentially expressed genes related to lung cancer metastasis and stemness were screened by differential analysis and lasso regression. Then, in vitro, experiments such as colony formation assay, scratch assay, and transwell assay were conducted to evaluate the impact of CDC45 knockdown on the proliferation and migration abilities of lung cancer cells. Western blotting was used to measure the expression levels of related proteins and investigate the regulation of CDC45 on the cell cycle. Finally, in vivo model with subcutaneous injection of lung cancer cells was performed to verify the effect of CDC45 on tumor growth. RESULTS: This study identified CDC45 as a key gene potentially influencing tumor stemness and lymph node metastasis. Knockdown of CDC45 not only suppressed the proliferation and migration abilities of lung cancer cells but also caused cell cycle arrest at the G2/M phase. Further analysis revealed a negative correlation between CDC45 and cell cycle-related proteins, stemness-related markers, and tumor mutations. Mouse experiments confirmed that CDC45 knockdown inhibited tumor growth. CONCLUSION: As a novel regulator of stemness, CDC45 plays a role in regulating lung cancer cell proliferation, migration, and cell cycle. Therefore, CDC45 may serve as a potential target for lung cancer treatment and provide a reference for further mechanistic research and therapeutic development.

PTK6: An emerging biomarker for prognosis and immunotherapeutic response in clear cell renal carcinoma (KIRC).

Kidney renal clear cell carcinoma (KIRC), one of the most prevalent form of kidney carcinoma, is highly aggressive cancer known for significant immune infiltration and high mortality rates. The absence of sensitivity to traditional therapy has spurred the search for new treatments. Protein Tyrosine Kinase 6 (PTK6) is implicated in promoting cancer growth, spread, and metastasis. Our review of The Cancer Genome Atlas database revealed PTK6 overexpression in KIRC, though its specific role in this cancer type was unclear. We investigated PTK6's cancer-promoting roles in KIRC using the database and confirmed our findings with patient-derived tissues. Our analysis showed that elevated PTK6 expression is linked to worse outcomes and higher levels of immune infiltration. It also correlates positively with neo-antigens (NEO) and DNA ploidy changes in KIRC. This research delves into PTK6's role in KIRC development, suggesting PTK6 as a possible biomarker for prognosis and treatment in KIRC.

MicroRNA-144-3p Inhibits Host Lipid Catabolism and Autophagy by Targeting PPARα and ABCA1 During Mycobacterium Tuberculosis Infection.

MicroRNA-mediated metabolic reprogramming recently has been identified as an important strategy for Mycobacterium tuberculosis (Mtb) to evade host immune responses. However, it is unknown what role microRNA-144-3p (miR-144-3p) plays in cellular metabolism during Mtb infection. Here, we report the meaning of miR-144-3p-mediated lipid accumulation for Mtb-macrophage interplay. Mtb infection was shown to upregulate the expression of miR-144-3p in macrophages. By targeting peroxisome proliferator-activated receptor α (PPARα) and ATP-binding cassette transporter A1 (ABCA1), miR-144-3p overexpression promoted lipid accumulation and bacterial survival in Mtb-infected macrophages, while miR-144-3p inhibition had the opposite effect. Furthermore, reprogramming of host lipid metabolism by miR-144-3p suppressed autophagy in response to Mtb infection. Our findings uncover that miR-144-3p regulates host metabolism and immune responses to Mtb by targeting PPARα and ABCA1, suggesting a potential host-directed tuberculosis therapy by targeting the interface of miRNA and lipid metabolism.

PD-1 and LAG-3 positive T cells are related with the prognosis of patients with chronic kidney disease.

OBJECTIVE: Our objective was to study the frequency of circulating LAG-3+ and PD-1+ T cells in chronic kidney disease (CKD) patients and their correlation with cytokines and patient prognosis. METHODS: A total of 83 patients with CKD between June 2020 and June 2022 were enrolled. We measured serum levels of IL-6, CRP, IL-1ß, and TNF-α by ELISA. The frequency of PD-1+ and LAG-3+ T cells was measured using flow cytometry. All patients were followed up for 1 year, and the occurrence of any of the following conditions during the follow-up period was considered as major adverse cardiac events (MACE) indicating poor prognosis. RESULTS: The frequencies of LAG-3+PD-1+, LAG-3+ and PD-1+ cells were significantly increased in CKD group compared to healthy volunteers. Additionally, CKD patients had remarkably enhanced levels of cytokines. Compared to the non-MACE group, MACE group had significantly higher frequencies of LAG-3PD-1, LAG-3 and PD-1 expression on CD8 and CD4. Positive correlations were observed between IL-1ß, IL-6 and frequencies of PD-1+LAG-3+. CD4+LAG-3+PD-1+ frequency displayed the highest diagnostic value for CKD patients with MACE. Moreover, CD8+LAG-3+, CD4+LAG-3+PD-1+, CD4+PD-1+, IL-1ß and IL-6 were identified as risk factors for the occurrence of MACE in patients with CKD. CONCLUSION: In summary, the present research showed that the frequencies of LAG-3+ and PD-1+ T cells were remarkably enhanced in CKD patients. These findings offer novel insights and potential therapeutic targets for the management of CKD.