Efficacy of astragalus combined with renin-angiotensin-aldosterone system blockers in the treatment of stage III diabetic nephropathy: a systematic review and meta-analysis.

OBJECTIVE: To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by meta-analysis. METHODS: PubMed, Embase, Cochrane Library, Wiley, and Web of Science databases were searched for articles published between August 2007 and August 2022. Clinical studies on Astragalus combined with RAAS blockers for the treatment of stage III DN were included. Meta-analysis was performed by RevMan 5.1 and Stata 14.3 software. RESULTS: A total of 32 papers were included in this meta-analysis, containing 2462 patients from randomized controlled trials, with 1244 receiving the combination treatment and 1218 solely receiving RAAS blockers. Astragalus combined with RAAS blockers yielded a significantly higher total effective rate (TER) (mean difference [MD] 3.63, 95% confidence interval [CI] 2.59-5.09) and significantly reduced urinary protein excretion rate (UPER), serum creatinine (Scr), blood urine nitrogen (BUN) and glycosylated hemoglobin (HbAlc) levels. In subgroup analysis, combining astragalus and angiotensin receptor blocker significantly lowered fasting plasma glucose (FPG) and 24 h urinary protein (24hUTP) levels, compared with the combined astragalus and angiotensin-converting enzyme inhibitor treatment. Meanwhile, the latter significantly decreased the urinary microprotein (ß2-MG). Importantly, the sensitivity analysis confirmed the study's stability, and publication bias was not detected for UPER, BUN, HbAlc, FPG, or ß2-MG. However, the TER, SCr, and 24hUTP results suggested possible publication bias. CONCLUSIONS: The astragalus-RAAS blocker combination treatment is safe and improves outcomes; however, rigorous randomized, large-scale, multi-center, double-blind trials are needed to evaluate its efficacy and safety in stage III DN.

Renin-angiotensin-aldosterone system (RAAS) inhibitors are commonly used to treat diabetic neuropathy (DN) and Astragalus membranaceus components are known to improve DN symptoms.We aimed to establish the efficacy and safety of using Astragalus combined with RAAS inhibitors.Astragalus combined with RAAS inhibitors enhances the total effective rate of diabetic neuropathy response to treatment and reduces urinary protein excretion rate, serum creatinine, blood urea nitrogen and HbAlc.Sensitivity analysis affirms study stability, while publication bias was detected for total effective rate, serum creatinine, and 24 h urinary protein levels.

Ruthenium Complexes with NNN-Pincer Ligands for N-Methylation of Amines Using Methanol.

A series of ruthenium complexes (Ru1-Ru4) bearing new NNN-pincer ligands were synthesized in 58-78% yields. All of the complexes are air and moisture stable and were characterized by IR, NMR, and high-resolution mass spectra (HRMS). In addition, the structures of Ru1-Ru3 were confirmed by X-ray crystallographic analysis. These Ru(II) complexes exhibited high catalytic efficiency and broad functional group tolerance in the N-methylation reaction of amines using CH3OH as both the C1 source and solvent. Experimental results indicated that the electronic effect of the substituents on the ligands considerably affects the catalytic reactivity of the complexes in which Ru3 bearing an electron-donating OMe group showed the highest activity. Deuterium labeling and control experiments suggested that the dehydrogenation of methanol to generate ruthenium hydride species was the rate-determining step in the reaction. Furthermore, this protocol also provided a ready approach to versatile trideuterated N-methylamines under mild conditions using CD3OD as a deuterated methylating agent.

Sub-inhibitory concentrations of tetrabromobisphenol A induce the biofilm formation of methicillin-resistant Staphylococcus aureus.

Biofilm formation by methicillin-resistant Staphylococcus aureus (MRSA) on indwelling medical devices complicates the treatment of infection. Tetrabromobisphenol A (TBBPA), a synthetic, lipophilic, halogenated aromatic compound widely used as an additive in plastics and electronic products, has raised environmental concerns due to its potential for bioaccumulation. This study investigated the impact of sub-inhibitory concentrations of TBBPA on MRSA biofilm formation. Crystal violet staining and confocal laser scanning microscopy analysis demonstrated that 1/8 MIC (0.5 µg/mL) of TBBPA significantly stimulated MRSA biofilm formation (P < 0.0001). MTT assays indicated that the metabolic activity within the biofilms increased by 15.60-40.85% compared to untreated controls. Dot blot immunoassay, autolysis assay, and extracellular DNA (eDNA) quantification further revealed TBBPA enhanced the production of polysaccharide intercellular adhesin (PIA) and eDNA, which are key biofilm components. Additionally, TBBPA was found to enhance the production of staphyloxanthin, facilitating MRSA survival under oxidative conditions and in human whole blood. RT-qPCR analysis showed that TBBPA significantly upregulated genes associated with biofilm formation (icaA, atlA, sarA), staphyloxanthin biosynthesis (crtM and sigB), and oxidative stress responses (sodA and katA). These findings suggest that TBBPA promotes MRSA biofilm development and enhances bacterial resistance to adverse conditions, thereby potentially exacerbating risks to human health.

Establishment of RNAi-Mediated Pest Control Method for Red Imported Fire Ant, Solenopsis invicta.

RNAi plays a crucial role in insect gene function research and pest control field. Nonetheless, the variable efficiency of RNAi across diverse insects and off-target effects also limited its further application. In this study, we cloned six essential housekeeping genes from Solenopsis invicta and conducted RNAi experiments by orally administering dsRNA. Then, we found that mixing with liposomes significantly enhanced the RNAi efficiency by targeting for SiV-ATPaseE. Additionally, we observed a certain lethal effect of this dsRNA on queens by our established RNAi system. Furthermore, no strict sequence-related off-target effects were detected. Finally, the RNAi effect of large-scale bacteria expressing dsRNA was successfully confirmed for controlling S. invicta. In summary, this study established an RNAi system for S. invicta and provided a research template for the future development of nucleic acid drugs based on RNAi.

A biosensor method based on surfactant-mediated surface droplet evaporation for the detection of Aflatoxin B1.

Aflatoxin B1 (AFB1) is a common mycotoxin that is of significant global concern due to its impact on food safety. Herein, we innovatively develop a sensing platform to detect AFB1 based on evaporation of surfactant solutions on the hydrophobic surface, resulting in dried patterns with varied sizes. The surfactant CTAB solution produces a relatively large dried pattern due to the surface wetting. However, the reduction in the dried pattern size is found when the mixture of CTAB and AFB1 aptamer is tested, because the formation of CTAB/aptamer complex. Moreover, the dried pattern size of the mixture of CTAB, aptamer, and AFB1 increases due to the specific binding of AFB1 to its aptamer. Using this innovative strategy, the AFB1 detection can be fulfilled with a detection limit of 0.77 pg/mL. As a simple, convenient, inexpensive, and label-free method, the surfactant-mediated surface droplet evaporation-based biosensor is very promising for various potential applications.

Comparing the clinical outcomes of initial surgery and primary definitive radiotherapy with a dosage of 6600 cGy or higher in cT1-2N0M0 oral cavity squamous cell carcinoma: A nationwide cohort study.

BACKGROUND: To compare the clinical outcomes of two treatment modalities, initial surgery and primary definitive radiotherapy (RT), in Taiwanese patients diagnosed with cT1-2N0M0 oral cavity squamous cell carcinoma (OCSCC). METHODS: Between 2011 and 2019, we analyzed data for 13,542 cT1-2N0M0 patients who underwent initial surgery (n = 13,542) or definitive RT with a dosage of at least 6600 cGy (n = 145) for the treatment of OCSCC. To account for baseline differences, we employed propensity score (PS) matching, resulting in two well-balanced study groups (initial surgery, n = 580; definitive RT, n = 145). RESULTS: Before PS matching, the 5-year disease-specific survival (DSS) rates were 88% for the surgery group and 58% for the RT group. After PS matching, the 5-year DSS rates of the two groups were 86% and 58%, respectively. Similarly, the 5-year overall survival (OS) rates before PS matching were 80% for the surgery group and 36% for the RT group, whereas after PS matching, they were 73% and 36%, respectively. All these differences were statistically significant (p < 0.0001). A multivariable analysis identified treatment with RT, older age, stage II tumors, and a higher burden of comorbidities as independent risk factors for both DSS and OS. We also examined the 5-year outcomes for various subgroups (margin ≥5 mm, margin <5 mm, positive margins, RT combined with chemotherapy, and RT alone) as follows: DSS, 89%/88%/79%/63%/51%, respectively, p < 0.0001; OS, 82%/79%/68%/39%/32%, respectively, p < 0.0001. CONCLUSIONS: In Taiwanese patients with cT1-2N0M0 OCSCC, a remarkably low proportion (1.1%) completed definitive RT. A significant survival disparity of 30% was observed between patients who underwent initial surgery and those who received definitive RT. Interestingly, even patients from the surgical group with positive surgical margins exhibited a significantly superior survival compared to those in the definitive RT group.

Informing the Need for a SARS-CoV-2 Booster Based Upon the Immune Responses among Young Healthy Adults to Variants Circulating in Late 2023.

BACKGROUND: COVID-19 remains a global public health challenge due to new immune-evasive SARS-CoV-2 variants and heterogeneous immunity. METHODS: In this cross-sectional study, we evaluated the adaptive immune responses in U.S. active-duty personnel who completed a COVID-19 primary vaccine series and with heterogenous SARS-CoV-2 vaccination and infection histories to 3 previously dominant variants (Ancestral, Delta, BA.5) and 3 circulating variants (XBB.1.5, EG.5, and BA.2.86) in late 2023. Analyses were performed based upon timing (within or beyond 12 months) and type (vaccine or infection) of the most recent exposure. RESULTS: Significant reduction was observed in binding antibodies, neutralization antibodies, memory B cells, and CD8+ T cells against circulating variants compared to previous variants. The reduction in antibody response was more pronounced in those whose most recent exposure was greater than 12 months from enrollment. In contrast, the CD4+ T cell response was largely consistent across all tested variants. The type of most recent exposure was not a significant factor in determining the magnitude of current immune responses. CONCLUSIONS: Administration of the XBB.1.5-based booster is likely to enhance cross-reactive humoral responses against SARS-CoV-2 circulating lineages. Ongoing surveillance of immune responses to emerging variants is needed for informing vaccine composition and timing.

Development and validation of a machine-learning model for predicting the risk of death in sepsis patients with acute kidney injury.

The mortality rate of patients with sepsis-induced acute kidney injury (S-AKI) is notably elevated. The initial categorization of prognostic indicators has a beneficial impact on elucidating and enhancing disease outcomes. This study aimed to predict the mortality risk of S-AKI patients by employing machine learning techniques. The sample size determined by a four-step procedure yielded 1508 samples. The research design necessitated the inclusion of individuals with S-AKI from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The patients were initially admitted to the Intensive Care Unit (ICU) for their hospital stay. Additionally, these patients (aged from 18 to 89 years old) had encountered S-AKI on the day of their admittance. Forty-two predictive factors were analyzed, with hospitalization death as the outcome variable. The training set (4001 cases) consisted of 70 % of the participants, and the remaining (1714 cases) participants were allocated to the validation set. Furthermore, an additional validation set (MIMIC-III) consisted of 1757 patients from the MIMIC-III database. Moreover, an external validation set from the Intensive Care Department of Beijing Friendship Hospital (BFH) comprised 72 patients. Six machine learning models were employed in the prediction, namely the logistic, lasso, rpart, random forest, xgboost, and artificial neural network models. The comparative efficacy of the newly developed model in relation to the APACHE II model for predicting mortality risk was also assessed. The XGBoost model exhibited a superior performance with the training set. With the internal validation set and the two external validation sets (MIMIC-III and BFH), the xgboost algorithm demonstrated the highest performance. Meanwhile, APACHE II performed poorly at predicting the mortality risk with the BFH validation set. The mortality risk was influenced by three primary clinical parameters: urine volume, lactate, and Glasgow Coma Scale (GCS) score. Thus, we developed a prediction model for the risk of death among S-AKI patients that has an improved performance compared to previous models and is a potentially valuable tool for S-AKI prediction and treatment in the clinic.

Beta 2-microglobulin is an independent risk marker of acute kidney injury in adult patients with hemophagocytic lymphohistiocytosis.

BACKGROUND AND AIMS: The role of beta2-microglobulin (ß2-MG) in predicting acute kidney injury (AKI) in hemophagocytic lymphohistiocytosis patients has been poorly studied. This study aimed to analyze the clinical characteristics of hemophagocytic lymphohistiocytosis patients and identify risk factors that predict AKI development. METHODS: This retrospective observational cohort study conducted at a single-center involved 938 patients diagnosed with hemophagocytic lymphohistiocytosis, who were divided into AKI  group and non-AKI group. Patient data were collected and analyzed using univariate and multivariate binary logistic regression to identify potiential risk factors associated with AKI occurrence.   RESULTS: Among the enrolled patients, 486 were male (51.9%), the median age was 37 years (interquartile range, 28.0, 52.0), 58.4% experienced AKI. Mechanical ventilation (8.0% vs. 0.8%) and vasopressor support (21.7% vs. 4.1%) occurred at significantly higher rates in the AKI group compared to the non-AKI group, with significantly higher in-hospital mortality (5.5% vs. 1.3%) and 28-day mortality (12.8% vs. 5.4%). When ß2-MG was used as a continuous variable, multifactorial analysis showed that ß2-MG, transplantation, and vasopressor support were independently associated with risk for the development of AKI. CONCLUSIONS: The incidence of morbidity and mortality in patients with hemophagocytic lymphohistiocytosis complicated by AKI remains high. Monitoring levels of ß2-MG may provide clinicians with timely indicators of changes in renal function,  facilitating adjustments to treatment strategies.

An externally validated clinical-laboratory nomogram for myocardial involvement in adult idiopathic-inflammatory-myopathy patients.

OBJECTIVES: This study aimed at identifying clinical and laboratory risk factors for myocardial involvement (MI) in idiopathic inflammatory myopathies (IIMs) patients as well as constructing a risk-predicted nomogram for prediction and early identification of MI. METHODS: An IIMs cohort in southeastern China was constructed, including 504 adult IIMs patients who met the inclusion and exclusion criteria, and were hospitalized at four divisions of the First Affiliated Hospital, Zhejiang University School of Medicine from January 1st 2018 to April 30st 2022. After dividing patients into the training cohort and the validation cohort, risk factors for MI were identified through least absolute shrinkage and selection operator regression and multivariate logistic regression. A risk-predicted nomogram was established and validated internally and externally for discrimination, calibration and practicability. RESULTS: In this cohort, 17.7% of patients developed MI and the survival was significantly inferior to that of IIMs patients without MI (P < 0.001). In the training cohort, age > 55 years old (P < 0.001), disease activity > 10 points (P < 0.001), interleukin-17A (IL-17A) > 7.5 pg/ml (P < 0.001), lactic dehydrogenase (LDH) > 425 U/L (P < 0.001), anti-mitochondrial antibodies (AMAs, P = 0.017), and anti-MDA5 antibody (P = 0.037) were significantly correlated with development of MI. A nomogram was established by including the above values to predict MI and was found efficient in discrimination, calibration, and practicability through internal and external validation. CONCLUSION: This study developed and validated a nomogram model to predict the risk of MI in adult IIMs patients, which can benefit the prediction and early identification of MI as well as timely intervention in these patients.

Oral arsenic plus imatinib versus imatinib solely for newly diagnosed chronic myeloid leukemia: a randomized phase 3 trial with 5-year outcomes.

PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).

Deprotonated 2-thiolimidazole serves as a metal-free electrocatalyst for selective acetylene hydrogenation.

Metal-free catalysts offer a desirable alternative to traditional metal-based electrocatalysts. However, metal-free catalysts, featuring defined active sites, rarely show activities as promising as metal-based materials. Here we report 2-thiolimidazole as an efficient metal-free catalyst for selective electrocatalytic hydrogenation of acetylene into ethylene. Under alkaline conditions, the sulfhydryl and imino groups of 2-thiolimidazole are spontaneously deprotonated into dianions. Deprotonation thus enriches the negative charges of pyridinic N sites in 2-thiolimidazole to enhance the adsorption of electrophilic acetylene through the σ-configuration. Ethylene partial current densities show a volcano relationship with the negative charges of the pyridinic N sites in various imidazole derivatives. Consequently, the deprotonated 2-thiolimidazole exhibits an ethylene partial current density and faradaic efficiency competitive with metal-based catalysts like Cu and Pd. This work highlights the tunability and promising potential of metal-free molecules in electrocatalysis.

The effect of preoperative mechanical bowel preparation in paediatric bowel surgery on postoperative wound related complications: A meta-analysis.

Mechanical bowel preparation (MBP), a routine nursing procedure before paediatric bowel surgery, is widely should in clinical practice, but its necessity remains controversial. In a systematic review and meta-analysis, we evaluated the effect of preoperative MBP in paediatric bowel surgery on postoperative wound-related complications in order to analyse the clinical application value of MBP in paediatric bowel surgery. As of November 2023, we searched four online databases: the Cochrane Library, Embase, PubMed, and Web of Science. Two investigators screened the collected studies against inclusion and exclusion criteria, and ROBINS-I was used to evaluate the quality of studies. Using RevMan5.3, a meta-analysis of the collected data was performed, and a fixed-effect model or a random-effect model was used to analyse OR, 95% CI, SMD, and MD. A total of 11 studies with 2556 patients were included. Most of studies had moderate-to-severe quality bias. The results of meta-analysis showed no statistically significant difference in the incidence of complications related to postoperative infections in children with MBP before bowel surgery versus those with No MBP, wound infection (OR 1.11, 95% CI:0.76 ~ 1.61, p = 0.59, I2 = 5%), intra-abdominal infection (OR 1.26, 95% CI:0.58 ~ 2.77, p = 0.56, I2 = 9%). There was no significant difference in the risk of postoperative bowel anastomotic leak (OR 1.07, 95% CI:0.68 ~ 1.68, p = 0.78, I2 = 12%), and anastomotic dehiscence (OR 1.67, 95% CI:0.13 ~ 22.20, p = 0.70, I2 = 73%). Patients' intestinal obstruction did not show an advantage of undergoing MBP preoperatively, with an incidence of intestinal obstruction (OR 1.95, 95% CI:0.55 ~ 6.93, p = 0.30, I2 = 0%). Based on existing evidence that preoperative MBP in paediatric bowel surgery did not reduce the risk of postoperative wound complications, we cautiously assume that MBP before surgery is unnecessary for children undergoing elective bowel surgery. However, due to the limited number of study participants selected for this study and the overall low quality of evidence, the results need to be interpreted with caution. It is suggested that more high quality, large-sample, multicenter clinical trials are required to validate our findings.

Evaluation of aconitine cardiotoxicity with a heart-on-a-particle prepared by a microfluidic device.

A heart-on-a-particle model based on multicompartmental microgel is proposed to simulate the heart microenvironment and study the cardiotoxicity of drugs. The relevant microgel was fabricated by a biocompatible microfluidic-based approach, where heart function-related HL-1 and HUVEC cells were arranged in separate compartments. Finally, the mechanism of aconitine-induced heart toxicity was elucidated using mass spectrometry and molecular biotechnology.

Integrative analyses of whole-transcriptome sequencing reveals CeRNA regulatory network in pulmonary hypertension treated with FGF21.

Noncoding RNAs have been shown to play essential roles in hypoxic pulmonary hypertension (HPH). Our preliminary data showed that HPH is attenuated by fibroblast growth factor 21 (FGF21) administration. Therefore, we further investigated the whole transcriptome RNA expression patterns and interactions in a mice HPH model treated with FGF21. By whole-transcriptome sequencing, differentially expressed mRNAs, miRNAs, lncRNAs, and circRNAs were successfully identified in normoxia (Nx) vs. hypoxia (Hx) and Hx vs. hypoxia + FGF21 (Hx + F21). Differentially expressed mRNAs, miRNAs, lncRNAs, and circRNAs regulated by hypoxia and FGF21 were selected through intersection analysis. Based on prediction databases and sequencing data, differentially co-expressed mRNAs, miRNAs, lncRNAs, and circRNAs were further screened, followed by functional enrichment analysis. MAPK signaling pathway and epigenetic modification were enriched and may play fundamental roles in the therapeutic effects of FGF21. The ceRNA regulatory network of lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA was constructed with miR-7a-5p, miR-449c-5p, miR-676-3p and miR-674-3p as the core. In addition, quantitative real-time PCR experiments were employed to verify the whole-transcriptome sequencing data. The results of luciferase reporter assays highlighted the relationship between miR-449c-5p and XR_878320.1, miR-449c-5p and Stab2, miR-449c-5p and circ_mtcp1, which suggesting that miR-449c-5p may be a key regulator of FGF21 in the treatment of PH. Taken together, this study provides potential biomarkers, pathways, and ceRNA regulatory networks in HPH treated with FGF21 and will provide an experimental basis for the clinical application of FGF21 in PH.

Mex-3 RNA binding family member A (MEX3A)/circMPP6 complex promotes colorectal cancer progression by inhibiting autophagy.

RNA-binding proteins (RBPs)-RNA networks have contributed to cancer development. Circular RNAs (circRNAs) are considered as protein recruiters; nevertheless, the patterns of circRNA-protein interactions in colorectal cancer (CRC) are still lacking. Processing bodies (PBs) formed through liquid-liquid phase separation (LLPS) are membrane-less organelles (MLOs) consisting of RBPs and RNA. Previous evidence suggests a connection between PBs dynamics and cancer progression. Despite the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs, there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in CRC. Herein, we identify that MEX-3 RNA binding family member A (MEX3A), frequently upregulated in CRC tissues, predicts poorer patient survival. Elevated MEX3A accelerates malignance and inhibits autophagy of CRC cells. Importantly, MEX3A undergoes intrinsically disordered regions (IDRs)-dependent LLPS in the cytoplasm. Specifically, circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs proteins. The MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A (PDE5A) mRNA degradation, consequently leading to the aggressive properties of CRC cells. Clinically, CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall survival. Our findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation, which provides prognostic markers and/or therapeutic targets for CRC.

Heterogeneity in Measures of Illness among Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Is Not Explained by Clinical Practice: A Study in Seven U.S. Specialty Clinics.

Background: One of the goals of the Multi-site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM) study was to evaluate whether clinicians experienced in diagnosing and caring for patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) recognized the same clinical entity. Methods: We enrolled participants from seven specialty clinics in the United States. We used baseline data (n = 465) on standardized questions measuring general clinical characteristics, functional impairment, post-exertional malaise, fatigue, sleep, neurocognitive/autonomic symptoms, pain, and other symptoms to evaluate whether patient characteristics differed by clinic. Results: We found few statistically significant and no clinically significant differences between clinics in their patients' standardized measures of ME/CFS symptoms and function. Strikingly, patients in each clinic sample and overall showed a wide distribution in all scores and measures. Conclusions: Illness heterogeneity may be an inherent feature of ME/CFS. Presenting research data in scatter plots or histograms will help clarify the challenge. Relying on case-control study designs without subgrouping or stratification of ME/CFS illness characteristics may limit the reproducibility of research findings and could obscure underlying mechanisms.

Understanding Macrophage-Tumor Interactions: Insights from Single-Cell Behavior Monitoring in a Sessile Microdroplet System.

Interaction between tumor-associated macrophages and tumor cells is crucial for tumor development, metastasis, and the related immune process. However, the macrophages are highly heterogeneous spanning from anti-tumorigenic to pro-tumorigenic, which needs to be understood at the single-cell level. Herein, a sessile microdroplet system designed for monitoring cellular behavior and analyzing intercellular interaction, demonstrated with macrophage-tumor cell pairs is presented. An automatic procedure based on the inkjet printing method is utilized for the precise pairing and co-encapsulation of heterotypic cells within picoliter droplets. The sessile nature of microdroplets ensures controlled fusion and provides stable environments conducive to adherent cell culture. The nitric oxide generation and morphological changes over incubation are explored to reveal the complicated interactions from a single-cell perspective. The immune response of macrophages under distinct cellular microenvironments is recorded. The results demonstrate that the tumor microenvironment displays a modulating role in polarizing macrophages from anti-tumorigenic into pro-tumorigenic phenotype. The approach provides a versatile and compatible platform to investigate intercellular interaction at the single-cell level, showing promising potential for advancing single-cell behavior studies.

[Critical Review on Heavy Metal Contamination in Urban Soil and Surface Dust].

With the rapid urbanization and industrialization, heavy metal contamination in urban soil and surface dust has received particular attention due to its negative effects on the eco-environment and human health. Contamination and spatio-temporal characteristics, contamination sources, and source apportionment methods, as well as the ecological and health risks of heavy metals in urban soil and surface dust were reviewed. The knowledge gaps in current research and prospects of future works were proposed. Four key points were presented, including improving the research on the interaction mechanism of heavy metals in urban soil and surface dust under complex conditions, enriching verification methods to improve the source apportionment reliability of anthropogenic metals by receptor models, strengthening the research on chemical forms of heavy metals from different sources and their short-term accumulation processes in surface dust, and raising the credibility of ecological and health risk forecast of heavy metals by integrating the improved exposure parameters and chemical forms.