Optimizing treatment administration strategies using negative mNGS results in corticosteroid-sensitive diffuse parenchymal lung diseases.

Timely adjustments of antibiotic and corticosteroid treatments are vital for patients with diffuse parenchymal lung diseases (DPLDs). In this study, 41 DPLD patients with negative metagenomic next-generation sequencing (mNGS) results who were responsive to corticosteroids were enrolled. Among these patients, about 26.8% suffered from drug-induced DPLD, while 9.8% presented autoimmune-related DPLD. Following the report of the negative mNGS results, in 34 patients with complete antibiotics administration profiles, 79.4% (27/34) patients discontinued antibiotics after receiving negative mNGS results. Moreover, 70.7% (29/41) patients began or increased the administration of corticosteroid upon receipt of negative mNGS results. In the microbiota analysis, Staphylococcus and Stenotrophomonas showed higher detection rates in patients with oxygenation index (OI) below 300, while Escherichia and Stenotrophomonas had higher abundance in patients with pleural effusion. In summary, our findings demonstrated the clinical significance of mNGS in assisting the antibiotic and corticosteroid treatment adjustments in corticosteroid-responsive DPLD. Lung microbiota may imply the severity of the disease.

Remnant cholesterol is associated with the progression and regression of metabolic dysfunction-associated steatotic liver disease in Chinese adults.

BACKGROUND: The aim of this study was to explore the associations of serum remnant cholesterol (RC) levels with the progression and regression of metabolic dysfunction-associated steatotic liver disease (MASLD) in Chinese adults. METHODS: We conducted a cross-sectional study in 13,903 individuals who underwent transient elastography tests (cohort 1) and a longitudinal study in 17,752 individuals who underwent at least two health check-up exams with abdominal ultrasound (cohort 2). Anthropometric and biochemical parameters were collected. Serum RC levels were calculated. Noninvasive fibrosis indices such as FIB-4 were evaluated in cohort 2. RESULTS: In cohort 1, serum RC levels were positively and independently associated with the severity of hepatic steatosis and liver fibrosis according to logistic regression analysis. In cohort 2, baseline serum RC levels were increased in participants with the incidence of MASLD and decreased in participants with the regression of MASLD during the follow-up period. Baseline serum RC levels were independently associated with an increased risk of development and a decreased likelihood of regression of MASLD: the fully adjusted hazard ratios (HR) were 2.785 (95 % CI 2.332-3.236, P < 0.001) and 2.925 (95 % CI 2.361-3.623, P < 0.001), respectively. In addition, when we used FIB-4 to evaluate liver fibrosis, baseline serum RC levels were positively correlated with the incidence of high-intermediate probability of advanced fibrosis. However, we did not find an association between serum RC levels and the regression of liver fibrosis. CONCLUSION: Serum RC levels are independently correlated with the progression and regression of MASLD in Chinese adults, suggesting that RC may participate in the pathophysiological process of MASLD.

Study of Factors Influencing the Oral Bioaccessibility of Commonly Used and Detected Pesticides in Bananas and Mangoes Based on in vitro Methods.

Estimating the impact of pesticide residue bioaccessibility in fruits on dietary exposure is a complex task in human health risk assessment. This research investigated the bioaccessibility of ten commonly used and detected pesticides in bananas and mangoes, as well as the factors influencing it, using an in vitro model. The highest bioaccessibility was observed at pH levels of 2.5 and 6.5 in the gastric and intestinal stages, respectively. Bioaccessibility decreased significantly with increasing solid/liquid ratios for most pesticides. The consumption of protein and four dietary components (carbohydrates, protein, lipids, and dietary fiber) could significantly reduce pesticide bioaccessibility by 9.89-48.32% (p < 0.05). Bioaccessibility in oral and gastric stages among four populations followed the order of adults/the elderly > children > infants, due to decreasing concentrations of α-amylase and pepsin. Pesticides in bananas generally exhibited a higher bioaccessibility (18.65-82.97%) compared to that in mangoes (11.68-87.57%). Bioaccessibility showed a negative correlation with the Log P values of the target pesticide, while no clear relationship was found between bioaccessibility and initial pesticide concentrations. Incorporating bioaccessible pesticide concentrations into risk assessments could lower dietary risk estimates by 11.85-79.57%. Assessing human exposure to pesticides based on bioaccessibility would greatly improve the accuracy of the risk assessment.

Association of Mosaic Chromosomal Alterations and Genetic Factors with the Risk of Cirrhosis.

Background and Aims: Age-related mosaic chromosomal alterations (mCAs) detected from genotyping of blood-derived DNA are structural somatic variants that indicate clonal hematopoiesis. This study aimed to investigate whether mCAs contribute to the risk of cirrhosis and modify the effect of a polygenic risk score (PRS) on cirrhosis risk prediction. Methods: mCA call sets of individuals with European ancestry were obtained from the UK Biobank. The PRS was constructed based on 12 susceptible single-nucleotide polymorphisms for cirrhosis. Cox proportional hazard models were applied to evaluate the associations between mCAs and cirrhosis risk. Results: Among 448,645 individuals with a median follow-up of 12.5 years, we identified 2,681 cases of cirrhosis, 1,775 cases of compensated cirrhosis, and 1,706 cases of decompensated cirrhosis. Compared to non-carriers, individuals with copy-neutral loss of heterozygosity mCAs had a significantly increased risk of cirrhosis (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.12-1.81). This risk was higher in patients with expanded cell fractions of mCAs (cell fractions ≥10% vs. cell fractions <10%), especially for the risk of decompensated cirrhosis (HR 2.03 [95% CI 1.09-3.78] vs. 1.14 [0.80-1.64]). In comparison to non-carriers of mCAs with low genetic risk, individuals with expanded copy-neutral loss of heterozygosity and high genetic risk showed the highest cirrhosis risk (HR 5.39 [95% CI 2.41-12.07]). Conclusions: The presence of mCAs is associated with increased susceptibility to cirrhosis risk and could be combined with PRS for personalized cirrhosis risk stratification.

Fabric structure and polymer composition as key contributors to micro(nano)plastic contamination in face masks.

The surge in face mask use due to COVID-19 has raised concerns about micro(nano)plastics (MNPs) from masks. Herein, focusing on fabric structure and polymer composition, we investigated MNP generation characteristics, mechanisms, and potential risks of surgical polypropylene (PP) and fashionable polyurethane (PU) masks during their wearing and photoaging based on stereomicroscope, µ-Fourier transform infrared spectroscopy (µ-FTIR), and scanning electron microscope (SEM) techniques. Compared with new PP and PU masks (66 ± 16 MPs/PP-mask, 163 ± 83 MPs/PU-mask), single- and multiple-used masks exhibited remarkably increased MP type and abundance (600-1867 MPs/PP-mask, 607-2167 MPs/PU-mask). Disinfection exacerbated endogenous MP generation in masks, with washing (416 MPs/PP-mask, 30,708 MPs/PU-mask) being the most prominent compared to autoclaving (219 MPs/PP-mask, 553 MPs/PU-mask) and alcohol spray (162 MPs/PP-mask, 18,333 MPs/PU-mask). Photoaging led to massive generation of MPs (8.8 × 104-3.7 × 105 MPs/PP-layer, 1.0 × 105 MPs/PU-layer) and NPs (5.2 × 109-3.6 × 1013 NPs/PP-layer, 3.5 × 1012 NPs/PU-layer) from masks, presenting highly fabric structure-dependent aging modes as "fragmentation" for fine fiber-structure PP mask and "erosion" for 3D mesh-structure PU mask. The MNPs derived from PP/PU mask caused significant deformities of Zebrafish (Danio rerio) larvae. These findings underscore the potential adverse effects of masks on humans and aquatic organisms, advocating to enhance proper use and rational disposal for masks.

Prognostic and therapeutic potential of imbalance between PD-1+CD8 and ICOS+Treg cells in advanced HBV-HCC.

Over 50% of patients with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) are diagnosed at an advanced stage, which is characterized by immune imbalance between CD8+ T cells and regulatory T (Treg) cells that accelerates disease progression. However, there is no imbalance indicator to predict clinical outcomes. Here, we show that the proportion of CD8+ T cells decreases and Treg cells increases in advanced HBV-HCC patients. During this stage, CD8+ T cells and Treg cells expressed the coinhibitory molecule PD-1 and the costimulatory molecule ICOS, respectively. Additionally, the ratio between PD-1+CD8 and ICOS+Tregs showed significant changes. Patients were further divided into high- and low-ratio groups: PD-1+CD8 and ICOS+Tregs high- (PD-1/ICOShi) and low-ratio (PD-1/ICOSlo) groups according to ratio median. Compared with PD-1/ICOSlo patients, the PD-1/ICOShi group had better clinical prognosis and weaker CD8+ T cells exhaustion, and the T cell-killing and proliferation functions were more conservative. Surprisingly, the small sample analysis found that PD-1/ICOShi patients exhibited a higher proportion of tissue-resident memory T (TRM) cells and had more stable killing capacity and lower apoptosis capacity than PD-1/ICOSlo advanced HBV-HCC patients treated with immune checkpoint inhibitors (ICIs). In conclusion, the ratio between PD-1+CD8 and ICOS+Tregs was associated with extreme immune imbalance and poor prognosis in advanced HBV-HCC. These findings provide significant clinical implications for the prognosis of advanced HBV-HCC and may serve as a theoretical basis for identifying new targets in immunotherapy.

Lithium Pollution and Its Associated Health Risks in the Largest Lithium Extraction Industrial Area in China.

Lithium (Li) is an important resource that drives sustainable mobility and renewable energy. Its demand is projected to continue to increase in the coming decades. However, the risk of Li pollution has also emerged as a global concern. Here, we investigated the pollution characteristics, sources, exposure levels, and associated health risks of Li in the Jinjiang River basin, the largest area for Li2CO3 production in China. Our results revealed the dominant role of Li extraction activities in the pollution of the river, with over 95% of dissolved Li in downstream river water being emitted from this source. Moreover, the Li concentration in aquatic plants (i.e., water hyacinth) and animals (i.e., fish) significantly increased from upstream to downstream areas, indicating a significant risk to local aquatic ecosystems. More importantly, our study found that local residents were suffering potential chronic noncarcinogenic health risks primarily from consuming contaminated water and vegetables. We also investigated the pollution characteristics of associated elements present in Li ores (e.g., Rb, Cs, Ni, and F-). By uncovering the remarkable impact of Li extraction activities on the Li content in ecosystems for the first time, our study emphasizes the importance of evaluating Li pollution from Li-related industrial activities, including mining, extraction, and recovery.

Unveiling of the Co-Infection of Peste des Petits Ruminants Virus and Caprine Enterovirus in Goat Herds with Severe Diarrhea in China.

Here, we report the discovery of two viruses associated with a disease characterized by severe diarrhea on a large-scale goat farm in Jilin province. Electron Microscopy observations revealed two kinds of virus particles with the sizes of 150-210 nm and 20-30 nm, respectively. Detection of 276 fecal specimens from the diseased herds showed the extensive infection of peste des petits ruminants virus (63.77%, 176/276) and caprine enterovirus (76.81%, 212/276), with a co-infection rate of 57.97% (160/276). These results were partially validated with RT-PCR, where all five PPRV-positive and CEV-positive specimens yielded the expected size of fragments, respectively, while no fragments were amplified from PPRV-negative and CEV-negative specimens. Moreover, corresponding PPRV and CEV fragments were amplified in PPRV and CEV double-positive specimens. Histopathological examinations revealed severe microscopic lesions such as degeneration, necrosis, and detachment of epithelial cells in the bronchioles and intestine. An immunohistochemistry assay detected PPRV antigens in bronchioles, cartilage tissue, intestine, and lymph nodes. Simultaneously, caprine enterovirus antigens were detected in lung, kidney, and intestinal tissues from the goats infected by the peste des petits ruminants virus. These results demonstrated the co-infection of peste des petits ruminants virus with caprine enterovirus in goats, revealing the tissue tropism for these two viruses, thus laying a basis for the future diagnosis, prevention, and epidemiological survey for these two virus infections.

Dihydromyricetin ameliorates diabetic renal fibrosis via regulating SphK1 to suppress the activation of NF-κB pathway.

Dihydromyricetin (DHM) is a flavonoid from vine tea with broad pharmacological benefits, which improve inflammation by blocking the NF-κB pathway. A growing body of research indicates that chronic kidney inflammation is vital to the pathogenesis of diabetic renal fibrosis. Sphingosine kinase-1 (SphK1) is a key regulator of diabetic renal inflammation, which triggers the NF-κB pathway. Hence, we evaluated whether DHM regulates diabetic renal inflammatory fibrosis by acting on SphK1. Here, we demonstrated that DHM effectively suppressed the synthesis of fibrotic and inflammatory adhesion factors like ICAM-1, and VCAM-1 in streptozotocin-treated high-fat diet-induced diabetic mice and HG-induced glomerular mesangial cells (GMCs). Moreover, DHM significantly suppressed NF-κB pathway activation and reduced SphK1 activity and protein expression under diabetic conditions. Mechanistically, the results of molecular docking, molecular dynamics simulation, and cellular thermal shift assay revealed that DHM stably bound to the binding pocket of SphK1, thereby reducing sphingosine-1-phosphate content and SphK1 enzymatic activity, which ultimately inhibited NF-κB DNA binding, transcriptional activity, and nuclear translocation. In conclusion, our data suggested that DHM inhibited SphK1 phosphorylation to prevent NF-κB activation thus ameliorating diabetic renal fibrosis. This supported the clinical use and further drug development of DHM as a potential candidate for treating diabetic renal fibrosis.

Protective Effect of Deer Heart Peptide on Cardiac Injury in Mice.

Peptides are widely used as natural bio-small molecules because of their various pharmacological activities such as enhancing immunity, promoting wound healing, and improving inflammation. Alcoholic heart injury has become one of the major health problems worldwide, and alcohol consumption is now the main cause of alcoholic cardiomyopathy. In this study, deer heart peptides were extracted from deer hearts by enzymatic digestion and the antioxidant activity of deer heart peptides extracted at different times was evaluated by three in vitro antioxidant methods, and the active peptide with the best enzymatic effect has been selected for in vivo animal experiments. The anti-inflammatory and antioxidant properties of deer heart enzymatic extracts were evaluated in in vivo experiments in mice. In this study, mice were orally gavaged with white wine (12 mL/kg body weight) to induce a mouse model of cardiac injury, while mice were orally administered a single dose of 100 mg/kg/bw and 200 mg/kg/bw of deer heart enzyme digest and were examined for body weight, dietary intake, water intake, and coat gloss, as well as for general behaviors, adverse effects, and mortality. Histology, serum, anti-inflammatory factors, and oxidative stress parameters were subsequently assessed. In all modeled mice, no four-way or any significant behavioral changes were observed in all groups, but in the modeled group, mice showed weight loss, decreased diet and water intake, and decreased cardiac index. For in vivo tests, the extract inhibited the anti-inflammatory activity with a significant decrease in inflammatory factors of TNF-α, IL-6, and IL-1ß in cardiac tissues, a significant increase in serum levels of both CAT and SOD, an increase in MDA content, and a remarkable increase in the level of the marker CK in the cardiac myocardial enzyme profile. Significant improvement in myocardial disorders by deer heart peptide could be observed from heart tissue sections. The present study emphasizes the anti-inflammatory and antioxidant activity of deer heart peptide, an enzymatic digest of deer heart, which provides empirical as well as supportive role for the anti-inflammatory properties of traditional medicine.

Pilot-scale field studies on activated microbial remediation of petroleum-contaminated soil.

Soil contamination by petroleum, including crude oil from various sources, is increasingly becoming a pressing global environmental concern, necessitating the exploration of innovative and sustainable remediation strategies. The present field-scale study developed a simple, cost-effective microbial remediation process for treating petroleum-contaminated soil. The soil treatment involves adding microbial activators to stimulate indigenous petroleum-degrading microorganisms, thereby enhancing the total petroleum hydrocarbons (TPH) degradation rate. The formulated microbial activator provided a growth-enhancing complex of nitrogen and phosphorus, trace elements, growth factors, biosurfactants, and soil pH regulators. The field trials, involving two 500 m3 soil samples with the initial TPH content of 5.01% and 2.15%, were reduced to 0.41% and 0.02% in 50 days, respectively, reaching the national standard for cultivated land category II. The treatment period was notably shorter than the commonly used composting and bioaugmentation methods (typically from 8 to 12 weeks). The results indicated that the activator could stimulate the functional microorganisms in the soil and reduce the phytotoxicity of the contaminated soil. After 40 days of treatment, the germination rate of rye seeds increased from 20 to 90%, indicating that the microbial activator could be effectively used for rapid on-site remediation of oil-contaminated soils.

Robust, wide-range, and precise transmitter IQ impairment monitoring scheme for coherent digital subcarrier multiplexing systems.

In this Letter, we present a robust, wide-range, and precise monitoring scheme for transmitter (Tx) impairments in coherent digital subcarrier multiplexing (DSCM) systems. The proposed scheme employs frequency-domain pilot tones (FPTs) to compensate for frequency offset (FO), polarization aliasing, and carrier phase noise, thus isolating Tx impairments from channel distortions. It then implements 4 × 4 real-valued MIMO to compensate for Tx impairments by equalizing symmetric subcarriers. Tx impairment monitoring is derived from the equalizer coefficients. By considering the phase shift caused by Tx impairments, a wide-range and precise monitoring of Tx impairments including IQ skew, IQ phase, and gain imbalances is achieved. We experimentally validated our approach using a 48-GBaud, four-subcarrier, dual-polarization coherent DSCM system. The results confirm the method's capability for a wide-range, robust, and precise Tx impairment monitoring in coherent DSCM systems, maintaining performance even in the presence of ultra-fast polarization variation.

A pediatric patient with bilateral tracheobronchial foreign body successfully treated using surgical intervention with extracorporeal circulation: case report and literature review.

Unilateral Tracheobronchial foreign body (TFB) present a common clinical disease, whereas bilateral TFB is a rare and acute condition associated with high mortality rates. This case study discusses a pediatric patient hospitalized due to respiratory distress following accidental ingestion of peanut kernels. A plain chest CT scan revealed obstructive emphysema in the right main bronchus and a foreign body at the opening of the left main bronchus. Surgical removal of the bilateral TFB under extracorporeal circulation resulted in a successful postoperative recovery, leading to discharge on the 9th day. A comprehensive literature search was conducted across databases including PubMed, Web of Science, EMBASE, Cochrane Library, and CNKI, spanning publications from January 2014 to October 2023, utilizing keywords "bronchial foreign body" and "Peanut". After deduplication and relevance screening, 9 pertinent literature sources were included. The objective of this study is to enhance clinical practitioners' understanding of TFB management and improve diagnostic and treatment capabilities through analysis of age of onset, clinical manifestations, diagnosis, and treatment approaches in critically ill pediatric patients.

Non-invasive prediction of preeclampsia using the maternal plasma cell-free DNA profile and clinical risk factors.

Background: Preeclampsia (PE) is a pregnancy complication defined by new onset hypertension and proteinuria or other maternal organ damage after 20 weeks of gestation. Although non-invasive prenatal testing (NIPT) has been widely used to detect fetal chromosomal abnormalities during pregnancy, its performance in combination with maternal risk factors to screen for PE has not been extensively validated. Our aim was to develop and validate classifiers that predict early- or late-onset PE using the maternal plasma cell-free DNA (cfDNA) profile and clinical risk factors. Methods: We retrospectively collected and analyzed NIPT data of 2,727 pregnant women aged 24-45 years from four hospitals in China, which had previously been used to screen for fetal aneuploidy at 12 + 0 ~ 22 + 6 weeks of gestation. According to the diagnostic criteria for PE and the time of diagnosis (34 weeks of gestation), a total of 143 early-, 580 late-onset PE samples and 2,004 healthy controls were included. The wilcoxon rank sum test was used to identify the cfDNA profile for PE prediction. The Fisher's exact test and Mann-Whitney U-test were used to compare categorical and continuous variables of clinical risk factors between PE samples and healthy controls, respectively. Machine learning methods were performed to develop and validate PE classifiers based on the cfDNA profile and clinical risk factors. Results: By using NIPT data to analyze cfDNA coverages in promoter regions, we found the cfDNA profile, which was differential cfDNA coverages in gene promoter regions between PE and healthy controls, could be used to predict early- and late-onset PE. Maternal age, body mass index, parity, past medical histories and method of conception were significantly differential between PE and healthy pregnant women. With a false positive rate of 10%, the classifiers based on the combination of the cfDNA profile and clinical risk factors predicted early- and late-onset PE in four datasets with an average accuracy of 89 and 80% and an average sensitivity of 63 and 48%, respectively. Conclusion: Incorporating cfDNA profiles in classifiers might reduce performance variations in PE models based only on clinical risk factors, potentially expanding the application of NIPT in PE screening in the future.

Cell-free Nucleic Acid as Promising Diagnostic Biomarkers for Gastric Cancer: a Systematic Review.

Background: Gastric cancer (GC) is a common malignancy with early detection being crucial for survival. Liquid biopsy analysis using cell-free nucleic acid is a preferred method for detection. Hence, we conducted a systematic review to assess the diagnostic efficacy of cell-free nucleic acid markers for GC. Methods: We searched PubMed and ISI Web of Science databases for articles that conformed to our inclusion and exclusion criteria from 2012 to 2022. The following information was abstracted: first author, year of publication, country/region, age, male proportion, tumor stage for cases, specimen type, measurement method, targeted markers and diagnostic related indicators (including sensitivity, specificity, AUC, P-value). Results: Fifty-eight studies examined cell-free RNAs (cfRNAs) with a total of 62 individual circulating markers and 7 panels in serum or plasma, while 21 studies evaluated cell-free DNAs (cfDNAs) with 29 individual circulating markers and 7 panels. For individual cfRNAs, the median (range) sensitivity and specificity were 80% (21% - 98%) and 80% (54% - 99%), respectively. The median (range) sensitivity and specificity for cfRNA panels were 86% (83% - 90%) and 75% (60% - 98%), respectively. In comparison, the median (range) sensitivity and specificity reported for individual cfDNAs were 50% (18% - 96%) and 93% (57% - 100%), respectively, while cfDNA panels had a median (range) sensitivity and specificity of 85% (41% - 92%) and 73.5% (38% - 90%), respectively. The meta results indicate that cfRNA markers exhibit high sensitivity (80%) and low specificity (80%) for detecting GC, while cfDNA markers have lower sensitivity (59%) but higher specificity (92%). Conclusions: This review has demonstrated that cell-free nucleic acids have the potential to serve as useful diagnostic markers for GC. Given that both cfRNA and cfDNA markers have shown promising diagnostic performance for GC, the combination of the two may potentially enhance diagnostic efficiency.

Receiver in-phase and quadrature skew tolerant baud-rate timing recovery scheme for short-reach coherent optical interconnection.

A baud-rate sampling timing recovery (TR) scheme with receiver IQ skew tolerance is proposed and experimentally demonstrated. The proposed scheme performs independent TR for the in-phase and quadrature (IQ) tributary signals, thereby tracking the sampling phase error while naturally compensating for receiver IQ skew. The robustness of the IQ-independent TR to frequency offset (FO) and phase noise is theoretically analyzed. To address IQ misalignment caused by the IQ-independent TR, the use of pseudo-noise (PN) sequences for IQ frame synchronization is proposed. The proposed scheme achieves accurate timing recovery with hardware-efficient baud-rate sampling in the presence of receiver IQ skew, laying the foundation for stable performance of subsequent baud-rate equalization. The performance of the scheme is validated in a 56 GBaud polarization division multiplexed (PDM) 16QAM coherent experimental system. Experimental results demonstrate that the proposed scheme achieves similar BER performance to the modified Gardner + real-valued multiple-input multiple-output (RVMIMO) (@2 SPS) scheme. Moreover, the proposed scheme exhibits robustness to arbitrary IQ skew compared to the ABSPD + RVMIMO (@1 SPS) scheme.

Validation of Baveno VII criteria for clinically significant portal hypertension by two-dimensional shear wave elastography.

BACKGROUND: The Baveno VII consensus proposed criteria for the non-invasively diagnosis of clinically significant portal hypertension (CSPH) in patients with compensated advanced chronic liver disease (cACLD). The performance of Baveno VII criteria for assessing CSPH by two-dimensional shear wave elastography (2D-SWE) had not been well validated. We aimed to validate the performance of Baveno VII criteria for rule-in and rule-out CSPH by 2D-SWE. METHOD: This is an international multicenter study including cACLD patients from China and Croatia with paired liver stiffness measurement (LSM), spleen stiffness measurement (SSM) by 2D-SWE, and hepatic venous pressure gradient (HVPG) were included. CSPH was defined as HVPG ≥ 10 mmHg. RESULT: A total of 146 patients with cACLD were enrolled, and finally 118 patients were included in the analysis. Among them, CSPH was documented in 79 (66.9%) patients. Applying the Baveno VII criteria for rule-out CSPH by 2D-SWE, [LSM ≤ 15 kPa and platelet count ≥ 150 × 109/L] OR SSM < 21 kPa, could exclude CSPH with sensitivity > 90% (93.5 or 98.7%) but negative predictive value < 90% (74.1 or 85.7%). Using the Baveno VII criteria for rule-in CSPH by 2D-SWE, LSM ≥ 25 kPa OR SSM ≥ 50 kPa, could diagnose CSPH with 100% specificity and 100% positive predictive values. CONCLUSION: Baveno VII criteria by 2D-SWE showed a good diagnostic performance for ruling in but not for ruling out CSPH, which might become an emerging non-invasive elastography tool to select the patients who needed non-selective beta blocker therapy.

GRP78 recognizes EV-F 3D protein and activates NF-κB to repress virus replication by interacting with CHUK/IKBKB.

Enteroviruses are the causative agents associated with several human and animal diseases, posing a significant threat to human and animal health. As one of the host immune defense strategies, innate immunity plays a crucial role in defending against invading pathogens, where the host utilizes a variety of mechanisms to inhibit or eliminate the pathogen. Here, we report a new strategy for the host to repress enterovirus replication by the 78 kDa glucose-regulated protein (GRP78), also known as heat shock protein family A member 5 (HSPA5). The GRP78 recognizes the EV-encoded RNA-dependent RNA polymerases (RdRPs) 3D protein and interacts with the nuclear factor kappa B kinase complex (CHUK) and subunit beta gene (IKBKB) to facilitate the phosphorylation and nuclear translocation of NF-κB, which induces the production of inflammatory factors and leads to a broad inhibition of enterovirus replication. These findings demonstrate a new role of GRP78 in regulating host innate immunity in response to viral infection and provide new insights into the mechanism underlying enterovirus replication and NF-κB activation.IMPORTANCEGRP78 is known as a molecular chaperone for protein folding and plays a critical role in maintaining protein folding and participating in cell proliferation, cell survival, apoptosis, and metabolism. However, the functions of GRP78 to participate in enterovirus genome replication and innate immune responses are rarely documented. In this study, we explored the functions of the EV-3D-interacting protein GRP78 and found that GRP78 inhibits enterovirus replication by activating NF-κB through binding to EV-F 3D and interacting with the NF-κB signaling molecules CHUK/IKBKB. This is the first report that GRP78 interacts with CHUK/IKBKB to activate the NF-κB signaling pathway, which leads to the expression of the proinflammatory cytokines and inhibition of enterovirus replication. These results demonstrate a unique mechanism of virus replication regulation by GRP78 and provide insights into the prevention and treatment of viral infections.

Quantitative analysis of four PAHs in oily sludge by surface-enhanced Raman spectroscopy (SERS) combined with partial least squares regression (PLS) based on a novel nano-silver-silicon coupling substrate.

Polycyclic aromatic hydrocarbons (PAHs) present in oily sludge generated by the petroleum and petrochemical industries have emerged as a prominent concern within the realm of environmental conservation. The precise determination of PAHs holds immense significance in both petroleum geochemistry and environmental protection. In this study, a combination of surface-enhanced Raman spectroscopy (SERS) and solid-liquid extraction was employed for the screening of PAHs in oily sludge. Methanol was utilized as the extraction solvent for PAHs, while nanosilver-silicon coupling substrates were employed for their detection. The SERS spectrum was acquired using a portable Raman spectrometer. The nano silver-silicon coupling substrate exhibits excellent uniformity, with relative standard deviations (RSDs) of Phenanthrene, Fluoranthrene, Fluorene and Naphthalene (Phe, Flt, Flu and Nap) being 2.8%, 1.08%, 1.41%, and 5.44% respectively. Moreover, the limits of detection (LODs) achieved remarkable values of 0.542 µg/g, 0.342 µg/g, 0.541 µg/g, and 5.132 µg/g. The quantitative analysis of PAHs in oily sludge was investigated using SERS technology combined with partial least squares (PLS). The optimal PLS calibration model was optimized by combining spectral preprocessing methods and using the SiPLS (Synergy interval partial least squares)-VIP (Variable Importance in Projection) hybrid variable selection strategy. The prediction performance of the D1st (First derivative)-WT (Wavelet transform)-SiPLS-VIP-PLS model was deemed satisfactory, as evidenced by high R2P values of 0.9851, 0.9917, and 0.9925 for Phe, Flt, and Flu respectively; additionally, the corresponding MREP values were found to be 0.0580, 0.0668, and 0.0669 respectively. However, for Nap analysis, the D1st-WT-PLS model proved to be a better calibration model with an R2P value of 0.9864 and an MREP (Mean relative error of prediction) value of 0.0713. In summary, SERS technology combined with PLS based on different spectral pretreatment methods and mixed variable selection strategies is a promising method for quantitative analysis of PAHs in oily sludge, which will provide new ideas and methods for the quantitative analysis of PAHs in oily sludge.