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Chenlu Huang,1,* Weixia Li,2,* Chong Chen,2,* Wei Xu,1 Ling Fei,1 Shuai Tao,3 Qiankun Hu,1 Xudong Xie,1 Xiongyue Cao,1 Xiao-Yu Zhang,1,4 Liang Chen,1 Qiang Li,1 Yuxian Huang1 1Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China; 2Department of Infectious Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China; 3Research Unit, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China; 4Section of Education, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuxian Huang; Qiang Li, Email yxhuang@fudan.edu.cn; liqiang66601@163.comAim: The early prognosis evaluation of acute-on-chronic liver failure (ACLF) is important to decrease its mortality. We aimed to develop a new score to accurately predict the outcome of patients with ACLF.Methods: A derivation set of 408 patients with hepatitis B virus-related ACLF (HBV-ACLF) based on the Asian Pacific Association for the Study of the Liver criteria is used to develop a prognostic score that was validated in 209 patients with HBV-ACLF and 195 patients with non-HBV-ACLF.Results: Seven factors were significantly related to the 28-day mortality and constituted a new score (CHINAT-CD4 = 0.320 × ln (creatinine) + 0.668 × hepatic encephalopathy score + 0.745 × ln (international normalized ratio) + 0.476 × ln (neutrophil) + 0.251 × ln (aspartate aminotransferase) + 0.411 × ln (total bilirubin) - 0.605 × ln (CD4+ T cells count)). The C-indices of the new score for the 28-/90-day mortality (0.810/0.806) outperformed those of the other seven scores (p≤ 0.05). The results were confirmed in a validation set (0.798/793 for HBV-ACLF; 0.790/0.788 for non-HBV-ACLF). The novel score based on CD4+ T cell count showed high predictive performance for the 28-/90-day mortality of ACLF.Conclusion: The novel score based on CD4+ T cell count can accurately predict the 28-/90-day mortality for patients with ACLF.Keywords: liver failure, chronic liver disease, prognostic score, risk stratification, inflammatory markers

Vegetation information is a critical factor in regional environment management under climate change. In this study, a typical arid and semi-arid watershed on the Loess Plateau, the Zu Li River Basin (ZRB), was selected to study the long-term changes in vegetation cover and its drivers and impacts. Unlike existing normalized vegetation index (NDVI) products, which have coarse spatial resolution and short time horizons, this study used the 30 m Landsat dataset analyzed in the Google Earth Engine (GEE) to generate high-resolution and long-term NDVI data, which are the most ideal for monitoring vegetation dynamics using long-time-series data products. The results showed that the annual mean maximum NDVI (normalized vegetation index) in the ZRB increased during 1987–2021, with a significant (p < 0.05) increasing trend in most areas. Upstream vegetation cover increased more than midstream and downstream, but the increase was smaller. Precipitation in the ZRB area was significantly (p < 0.05) correlated with the NDVI series, except for the upstream pass area, where human activities played an important role. NDVI was significantly (p < 0.05) negatively correlated with runoff coefficient and sand content, indicating that vegetation cover was an important reason for the decrease in runoff coefficient and sand content.

Wei Xu,* Chenlu Huang,* Ling Fei,* Qiang Li, Liang Chen Department of Liver Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiang Li; Liang Chen Email liqiang66601@163.com; chenliang@shphc.org.cnObjective: To describe the longitudinal changes in liver function tests, and their association with illness severity and mortality in patients with COVID-19.Methods: A retrospective cohort study of 1003 hospitalized patients with COVID-19 was conducted. Longitudinal liver function tests and clinical outcomes were analyzed.Results: Abnormal liver function parameters were observed, both at admission (ALT 13.2%, AST 8.5%, ALP 2.0%, GGT 7.4%, LDH 37.6%, TBIL 4.0%, DBIL 7.8%, Albumin 10.1%) and peak hospitalization (ALT 29.4%, AST 17.5%, ALP 2.6%, GGT 13.4%, LDH 49.4%, TBIL 10.1%, DBIL 18.0%, Albumin 30.6%) in patients with COVID-19. Compared with non-severe patients, severe patients had markedly higher liver function parameters from baseline to 30 days after hospital admission. Abnormal ALT and LDH at hospital admission and some medications use (Hydroxychloroquine, Lopinavir/Ritonavir, and Traditional Chinese medicines) were associated with peak hospitalization ALT > 5× the upper limit unit of normal (ULN). On multivariate analysis, age > 60 years, male, obesity, comorbidity, abnormal LDH and albumin at hospital admission and peak hospitalization were associated with progression to severe COVID-19 (OR > 1; p < 0.05). COX analysis revealed that ALT > 2 ULN (HR=7.0, p=0.011), AST > 2 ULN (HR=34.7, p < 0.001), and TBIL > 2 ULN (HR=54.6, p < 0.001) were associated with a higher mortality.Conclusion: Dynamic abnormalities of liver function parameters are common in hospitalized patients with COVID-19, and associated with illness severity and mortality.Keywords: COVID-19, SARS-CoV-2, liver function parameters, liver injury, clinical outcomes

This study aimed to explore the value of baseline serum exosome-derived miRNAs for predicting HBeAg seroconversion in chronic hepatitis B (CHB) patients treated with peginterferon (Peg-IFN). A total of 120 treatment-naive HBeAg-positive CHB patients who received Peg-IFN therapy (48 weeks) were enrolled. Next-generation sequencing was performed to screen the serum exosomal miRNAs that were associated with Peg-IFN treatment outcome, and qRT-PCR was used to validate them. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the predictive efficacy of biomarkers. Thirty-three patients (27.5%) achieved HBeAg seroconversion (response group), and 87 patients (72.5%) did not achieve HBeAg seroconversion (nonresponse group). In the identification cohort, 40 serum exosome-derived miRNAs were differentially expressed between the response group (four patients) and the nonresponse group (four patients). In the confirmation cohort, the expression levels of serum exosomal miR-194-5p (p < .001) and miR-22-3p (p < .001) were significantly downregulated in the response group (29 patients) compared to the nonresponse group (83 patients). Multivariate analysis identified baseline serum exosomal miR-194-5p, miR-22-3p, alanine aminotransferase (ALT), and HBV DNA as independent predictors of HBeAg seroconversion (all p < .05). The AUROCs of serum exosomal miRNAs (0.77 and 0.75 for miR-194-5p and miR-22-3p, respectively) were higher than that of ALT (0.70) and HBV DNA (0.69). The combination of exosomal miR-194-5p and miR-22-3p further improved the predictive performance with an AUROC of 0.82. Baseline serum exosomal miR-194-5p and miR-22-3p may serve as novel biomarkers to predict HBeAg seroconversion in CHB patients treated with Peg-IFN.

Combination therapy such as photothermal therapy (PTT) enhanced chemotherapy is regarded as a promising strategy for cancer treatment. Herein, we developed redox-responsive polymeric vesicles based on the amphiphilic triblock copolymer PCL-ss-PEG-ss-PCL. To avoid the limited therapeutic effect of chemotherapeutic drugs caused by systemic exposures and drug resistance, the redox-sensitive polymeric vesicles were cargoed with two chemotherapeutics: doxorubicin (DOX) and paclitaxel (PTX). Besides, indocyanine green (ICG) was encapsulated, and cell-penetrating peptides and LHRH targeting molecule were modified on the surface of polymeric vesicles. The results indicated that the polymeric vesicles can load different kinds of drugs with high drug loading content, trigger drug release in responsive to the reductive environment, realize high cellular uptake via dual peptides and laser irradiation, and achieve higher cytotoxicity via chemo-photothermal combination therapy. Hence, the redox-responsive LHRH/TAT dual peptides-conjugated PTX/DOX/ICG co-loaded polymeric micelles exhibited great potential in tumor-targeting and chemo-photothermal therapy.

Soil erosion is a very complex physical and geographical phenomenon, which is affected by both natural and human activities. Based on theoretical and technical methods such as CSLE model, Classification and Regression Tree (CART) and Google Earth Engine (GEE), on the basis of obtaining medium and high resolution soil erosion factors, this study systematically analyzed the temporal and spatial variation of soil erosion rate on the Loess Plateau in the past 40 years and the changes of the main controlling factors of soil erosion before and after “returning farmland to forest (grass)”. The main conclusions are as follows: (1) The soil erosion rates of the Loess Plateau in 1980, 1990, 2000, 2010, and 2017 were 2207.57, 1725.13, 981.18, 727.79, and 640.00 t/(km2∙a), showing a decreasing trend overall. As the most serious soil erosion area on the Loess Plateau, the Loess Hilly and Gully region has a significant weakening trend in its soil erosion rate, but its five-phase average soil erosion rate is still more than twice the average of the whole region, 4414.77, 3485.19, 1884.37, 1296.21, 1135.04 t/(km2∙a). (2) Before returning farmland to forest (grass) (before 1999), rainfall erosivity (R) was the main controlling factor for soil erosion. After the large-scale implementation of various soil and water conservation measures, the influence of biological measures (B) on soil erosion rate increased; in the sandy region of the Loess Plateau dominated by low-coverage grasslands, soil erosion was significantly affected by rainfall erosivity (R). The main controlling factors of soil erosion in the loess hilly and gully area changed significantly around 2000, from the combined effect of terrain (LS) and vegetation (B) to the combined effect of rainfall erosivity (R), gully erosion factor (g) and vegetation (B). (3) The average soil erosion rate under different land use types on the Loess Plateau is characterized by cultivated land>grassland>forest land. From 1980 to 2017, the soil erosion rate from cultivated land to forest land decreased the most, and the change slope was -74.84 (t/(km2∙a))/a, followed by cultivated land to grassland and grassland to forest land, both of which changed the slope of soil erosion. They are -51.88 (t/(km2∙a))/a and -49.05 (t/(km2∙a))/a, respectively. This research can provide a scientific basis for the needs of future comprehensive management planning and soil and water conservation construction in the basin.

This study aimed to evaluate the efficacy of Peg-interferon (Peg-IFN)–nucleoside analog (NA) sequential optimization therapy (SOT) in HBeAg-positive patients with chronic hepatitis B (CHB). In this prospective two-center study, 132 CHB patients were assigned to receive Peg-IFN standard therapy for 48 weeks (65 patients) or Peg-IFN monotherapy for 12–24 weeks and NA add-on for those without early virological response (EVR) (67 patients). Both patient groups were monitored and followed for 24 weeks after treatments stop. At week 24 after treatments stop, the Peg-IFN–NA SOT group achieved more HBsAg levels drop (− 1.35 vs − 0.67 log10 IU/mL, p = 0.016), higher HBsAg ≤ 100 IU/mL (32.8% vs 9.2%, p = 0.001), HBV DNA undetectable (79.1% vs 49.2%, p

Objectives This study aimed to observe the efficacy of corticosteroids in non-severe COVID-19 pneumonia. Methods A retrospective study based on propensity score matching was designed to explore the effects of corticosteroids. Primary outcomes included the rate of patients who developed severe disease and mortality. Secondary outcomes included duration of fever, virus clearance time, length of hospital stay, and the use of antibiotics. Results A total of 475 patients with non-severe COVID-19 pneumonia were enrolled, 55 patients received early, low-dose, and short-term corticosteroids therapy, 420 patients received non-corticosteroids therapy. Compared to the non-corticosteroids group, there was a prolonged duration of fever (median 5 vs 3 days, p

Hepatitis E virus (HEV) infection contributes to a considerable proportion of acute-on-chronic liver failure (ACLF) in patients with chronic hepatitis B virus (HBV) infection. This study aimed to predict the prognosis of chronic HBV infection patients precipitating acute HEV infection. A total of 193 patients were enrolled in this study. The performances of three chronic liver disease prognostic models (CTP score, MELD score, and CLIF-C ADs) were analyzed for predicting the development of ACLF following HEV superimposing chronic HBV infection. Subsequently, the performances of five ACLF prognostic assessment models (CTP score, MELD score, CLIF-C ACLFs, CLIF-C OFs, and COSSH-ACLFs) were analyzed for predicting the outcome of those ACLF patients. Of 193 chronic HBV infection patients precipitating acute HEV infection, 13 patients were diagnosed ACLF on admission, 54 patients developed to ACLF after admission, and 126 patients had non-ACLF during the stay in hospital. For predicting the development of ACLF, CTP score yielded a significantly higher AUROC compared with MELD score and CLIF-C ADs (0.92, 0.88, and 0.86, respectively; all p p

Chemophotothermal combination therapy has emerged as a novel and promising strategy to treat cancer. To improve anticancer effectiveness and reduce systemic toxicity, it is essential to trigger drug release at tumor sites or within tumor cells for maximal drug exposure. Herein, we constructed gas-generating mesoporous silica nanoparticles (MSNs) that can load ammonium bicarbonate (ABC) and doxorubicin (DOX) within the pores, encapsulate indocyanine green (ICG) onto the polydopamine (PDA) layer, and modify the RGD peptide on the outer surface [denoted as M(abc)-DOX@PDA-ICG-PEG-RGD] for triggered drug release and targeted chemophotothermal combination therapy. Upon hyperthermia or low pH value, the encapsulated ABC can efficiently generate CO2 gas, thus enhancing the damage to the PDA layer and accelerating DOX release. In vitro experiments showed that the M(abc)-DOX@PDA-ICG-PEG-RGD significantly enhanced cellular uptake and cytotoxicity, and laser irradiation further increased the endocytic and cytotoxic effects. An in vivo study indicated that the nanoparticles can effectively accumulate at the tumor site and significantly inhibited tumor growth with no side-effects to the normal organs. Thus, this gas-generating MSN-based nanocarrier that can trigger drug release in response to laser irradiation or low pH value holds great potential in enhancing cancer chemophotothermal combination therapy.

In this paper, a new Fourier-differential transform method (FDTM) based on differential transformation method (DTM) is proposed. The method can effectively and quickly solve linear and nonlinear partial differential equations with initial boundary value (IBVP). According to boundary condition, the initial condition is expanded into a Fourier series. After that, the IBVP is transformed to an iterative relation in K-domain. The series solution or exact solution can be obtained. The rationality and practicability of the algorithm FDTM are verified by comparisons of the results obtained by FDTM and the existing analytical solutions.

The aim of this study is to determine the role of serum exosomal miRNAs as potential non-invasive biomarkers for distinguishing no-or-mild fibrosis from significant fibrosis in patients with chronic hepatitis B (CHB).Next-generation sequencing was used to identify fibrosis-related serum exosomal miRNAs in 9 CHB patients. The candidate exosomal miRNAs were further validated by qRT-PCR in 282 CHB patients. Receiver operating characteristic curves were generated to assess the diagnostic performance of exosomal miRNAs and other non-invasive models.Seventy-two miRNAs were differentially expressed in serum exosomes between patients with no-or-mild fibrosis and significant fibrosis. The expression of serum exosomal miR-92a-3p and miR-146a-5p progressively increased with the aggravation of liver fibrosis in the validation cohort. Multivariate analysis identified miR-92a-3p (P0.001), miR-146a-5p (P0.001), and liver stiffness measurement (LSM) (P=0.012) as independent predictors for significant fibrosis. The area under the receiver operating characteristic curve (AUROC) of exosomal miR-92a-3p (AUROC=0.88) was significantly higher than that of APRI (aspartate aminotransferase-to-platelet ratio index) (AUROC=0.72, P0.001), FIB-4 (AUROC=0.71, P0.001), and LSM (AUROC=0.80, P=0.022) for identifying significant fibrosis. Similarly, the AUROC of exosomal miR-146a-5p (AUROC=0.82) was also significantly better than that of APRI (AUROC=0.72, P=0.009), FIB-4 (AUROC=0.71, P=0.002), and comparable to LSM (AUROC=0.80, P=0.551) for discriminating significant fibrosis.Serum exosomal miR-92a-3p and miR-146a-5p are superior to APRI, FIB-4, and LSM for diagnosing significant fibrosis in CHB patients and offer a promising non-invasive alternative to liver biopsy.

Soil erosion is serious in China—the soil in plateau and mountain areas contain a large of rock fragments, and their content and distribution have an important influence on soil erosion. However, there are still no complete results for calculating soil erodibility factor (K) that have corrected rock fragments in China. In this paper, the data available on rock fragments in the soil profile (RFP); rock fragments on the surface of the soil (RFS); and environmental factors such as elevation, terrain relief, slope, vegetation coverage (characterised by normalised difference vegetation index, NDVI), land use, precipitation, temperature, and soil type were used to explore the effects of content of soil rock fragments on calculating of K in China. The correlation analysis, typical sampling area analysis, and redundancy analysis were applied to analyse the effects of content of soil rock fragments on calculating of K and its relationship with environment factors. The results showed that (1) The rock fragments in the soil profile (RFP) increased K. The rock fragments on the surface (RFS) of the soil reduced K. The effect of both RFP and RFS reduced K. (2) The effect of rock fragments on K was most affected by elevation, followed by terrain relief, NDVI, slope, soil type, temperature, and precipitation, but had little correlation with land use. (3) The result of redundancy analysis showed elevation to be the main predominant factor of the effect of rock fragments on K. This study fully considered the effect of rock fragments on calculating of K and carried out a quantitative analysis of the factors affecting the effect of rock fragments on K, so as to provide necessary scientific basis for estimating K and evaluating soil erosion status in China more accurately.

We aimed to compare the dynamic differences of immunological parameters between severe and non-severe COVID-19 patients.The cytokine profiles and lymphocyte subsets of 664 patients with COVID-19 (31 severe cases and 633 non-severe cases) were longitudinally analyzed.Compared with non-severe cases, severe cases had a higher age (64 vs. 40 years, p0.001), more common comorbidity (74.2% vs. 20.5%, p0.001), and lymphopenia (0.7 vs. 1.4x109/L, p0.001). Severe cases had markedly higher levels of IL-6, IL-8, and IL-10 from baseline to 35 days after admission than non-severe cases (p0.001). No significant differences were observed in the dynamic levels of IL-1beta, IL-2, IL-4, IL-5, IL-12, IL-17, TNF-alpha, IFN-alpha, and IFN-gamma between severe and non-severe COVID-19 patients (p0.05). The absolute counts of lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, and CD45+ T cells were markedly lower in severe patients with COVID-19 compared with those in non-severe patients from baseline to 35 days after admission (p0.001). No significant differences were observed in the dynamic levels of white cells count, CD19+ B cells count, and NK cells count between severe and non-severe COVID-19 patients (p0.05). The decrease of T lymphocyte subsets reached its peak at day 1 to 3 after admission, and they gradually increased in the non-severe group, but sustained at low levels in the severe group at day 4 to 35 after admission.The dynamic changes of cytokine profiles and T lymphocyte subsets are related with the severity of COVID-19.

The progression of acute-on-chronic liver failure (ACLF) is associated with various factors, including inflammatory cells, cytokines, inflammatory mediators, and the gut microbiome. Acute insult activates immune cells which provokes cytokine and chemokine cascades and subsequently initiates hepatic damage, aggressive systemic inflammatory response syndrome (SIRS), and high mortality in patients with ACLF. Immune soluble components not only play a critical role in disease progression but also potentially correlates with clinical disease severity indices including Child-Turcotte-Pugh score, the model for end-stage liver disease (MELD) score, and sequential organ failure (SOF) score. Several immune soluble components lead to a better understanding of the pathophysiological basis of ACLF, and precise immune mechanisms offer therapeutic targets for ACLF. However, there are a number of specific issues that were not addressed unambiguously, such as whether dysfunctional immune soluble components are the cause or outcome of ACLF. Further evaluation and validation of emerging and relevant biomarkers will facilitate the formulation of a potential score which, either alone or in combination with existing scoring systems, will improve the clinical outcome prognostication and therapeutic efficacy of patients with ACLF. Extensive research is required to find out the mechanisms responsible for disease severity and high mortality in patients with ACLF.

Qinling Mountains is the north–south boundary of China’s geography, the vegetation changes are of great significance to the survival of wildlife and the protection of species habitats. Based on Landsat products in the Google Earth Engine (GEE) platform, Pearson’s correlation coefficient method, and classification and regression models, this study analyzed the changes in NDVI (Normalized Difference Vegetation Index) in the Qinling Mountains in the past 38 years and the sensitivity of its driving factors. Finally, residual analysis method and accumulate slope change rate are used to identify the impact of human activities and climate change on NDVI. The research results show the following: (1) The NDVI value in most areas of Qinling Mountains is at a medium-to-high level, and 99.76% of the areas correspond to an increasing trend of NDVI, and the significantly increased area accounts for more than 20%. (2) From 1981 to 2019, the NDVI of the Qinling Mountains increased from 0.63 to 0.78, showing an overall upward trend, and it increased significantly after 2006. (3) Sensitivity analysis results show that the western high-altitude area of Qinling Mountain area dominated by grassland is mainly affected by precipitation. The central and southeastern parts of the Qinling Mountains are significantly affected by temperature, and they are mainly distributed in areas dominated by forest. (4) The contribution rates of climate change and human activities to NDVI are 36.04% and 63.96%, respectively. Among them, the positive impact of human activities on the NDVI of the Qinling Mountains accounted for 99.85% of the area. The area with significant positive effect accounted for 36.49%. The significant negative effect area accounts for only 0.006%, mainly distributed in urban areas and coal mining areas.

International audience; Reconfigurable intelligent surface (RIS), one of the key enablers for the sixth-generation (6G) mobile communication networks, is considered by designers to smartly reconfigure the wireless propagation environment in a controllable and programmable manner. Specifically, an RIS consists of a large number of low-cost and passive reflective elements (REs) without radio frequency chains. The system gain of RIS wireless systems can be achieved by adjusting the phase shifts and amplitudes of the REs so that the desired signals can be added constructively at the receiver. However, an RIS typically has limited signal processing capability and cannot perform active transmitting/receiving in general, which leads to new challenges in the physical layer design of RIS wireless systems. In this paper, we provide an overview of the RIS-aided wireless systems, including the reflection principle, channel estimation, and system design. In particular, two types of emerging RIS systems are considered: RIS-aided wireless communications (RAWC) and RIS-based information transmission (RBIT), where the RIS plays the role of the reflector and the transmitter, respectively. We also envision the potential applications of RIS in 6G networks.

Objective: Thymosin alpha 1 (Thymosin-α1) is a potential treatment for patients with COVID-19. We aimed to determine the effect of Thymosin-α1 in non-severe patients with COVID-19.Methods: We retrospectively enrolled 1,388 non-severe patients with COVID-19. The primary and secondary clinical outcomes were evaluated with comparisons between patients treated with or without Thymosin-α1 therapy.Results: Among 1,388 enrolled patients, 232 patients (16.7%) received both Thymosin-α1 therapy and standard therapy (Thymosin-α1 group), and 1,156 patients (83.3%) received standard therapy (control group). After propensity score matching (1:1 ratio), baseline characteristics were well-balanced between the Thymosin-α1 group and control group. The proportion of patients that progressed to severe COVID-19 is 2.17% for the Thymosin-α1 group and 2.71% for the control group (p = 0.736). The COVID-19-related mortality is 0.54% for the Thymosin-α1 group and 0 for the control group (p = 0.317). Compared with the control group, the Thymosin-α1 group had significantly shorter SARS-CoV-2 RNA shedding duration (13 vs. 16 days, p = 0.025) and hospital stay (14 vs. 18 days, p < 0.001). No statistically significant difference was found between the Thymosin-α1 group and control group in duration of symptoms (median, 4 vs. 3 days, p = 0.843) and antibiotic utilization rate (14.1% vs. 15.2%, p = 0.768).Conclusion: For non-severe patients with COVID-19, Thymosin-α1 can shorten viral RNA shedding duration and hospital stay but did not prevent COVID-19 progression and reduce COVID-19-related mortality rate.

Highlights • No statistically significant differences were found between IVIg group and control group in the duration of fever, virus clearance time, length of hospital stay, and use of antibiotics. • Compared to IVIg therapy group, no more patients progressed to severe cases and died in control group. • In non-severe patients with COVID-19, no benefit was observed with IVIg therapy beyond standard therapy., Objectives At present, there is an absence of any proven effective anti-viral therapy for COVID-19 patients. This study aimed to assess the efficacy of intravenous immunoglobulin (IVIg) in non-severe patients with COVID-19. Methods A retrospective study based on propensity score matching (PSM) was designed. Primary outcomes included severity rate and mortality. Secondary outcomes included the duration of fever, virus clearance time, length of hospital stays, and use of antibiotics. Results 639 non-severe patients with COVID-19 were enrolled. 45 patients received IVIg therapy and 594 received non-IVIg therapy. After PSM (1:2 ration), the baseline characteristics were well balanced between IVIg (n = 45) and control group (n = 90). No statistically significant differences were found between IVIg group and control group in the duration of fever (median, 3 vs 3 days, p = 0.667), virus clearance time (median, 11 vs 10 days, p = 0.288), length of hospital stay (median, 14 vs 13 days, p = 0.469), and the use of antibiotics (40% vs 38.9%, p = 0.901). Meanwhile, compared to IVIg group, no more patients progressed to severe cases (3.3% vs 6.6%, p = 0.376) and died (0 vs 2.2%, p = 0.156) in control group. Conclusion In non-severe patients with COVID-19, no benefit was observed with IVIg therapy beyond standard therapy.

Liver injury has been reported as a common complication in Coronavirus disease 2019 (COVID-19). Recently, more and more studies reported that the degree of liver damages was associated with the severity of COVID-19. Although the exact mechanism of liver injury in COVID-19 patients is unknown, recent studies have made some explorations and investigations. In this review, we summarized the potential mechanisms of liver dysfunction in COVID-19 patients gleaned from recently published research reports, which suggested that the progression of pre-existing liver diseases, direct damage of liver by SARS-CoV-2, systemic inflammation caused by SARS-CoV-2 infection, anti-viral drug toxicity, and hypoxia-reperfusion may be associated with liver injury in patients with COVID-19. Hypoxic liver injury due to ischemia and shock, cholestasis-related liver injury due to altered bile metabolism, and hepatocellular injury due to drug toxicity or overwhelming inflammation might occur in severe COVID-19 patients with sepsis. To understand the pathogenesis of liver dysfunction in COVID-19 patients, further research is needed to focus on liver-related comorbidities, the evidence of viral replication in hepatocytes and bile duct cells, histological features of liver injury, and the influence of hepatotoxic antiviral drugs. We also suggested that special attention should be paid to monitoring inflammatory cytokines and hypoxia for the prevention and treatment of liver injury in severe COVID-19 patients. A deep understanding of the mechanism of liver injury is helpful for the management and treatment of COVID-19 patients.

This article first puts forward the shortcomings of current AMT starting control in the preface. Then, in the second chapter, the dynamic analysis of the starting process was carried out, and the three requirements of starting control were clarified: dynamic requirements, smoothness requirements and low slippage requirements; it was clarified that dynamic requirements were the main control objectives of starting control, smoothness Performance requirements and low clutch wear requirements are constraints. In the third chapter, the optimal control principle of the AMT starting is proposed; the clutch target engagement amount is determined according to the power requirements, the engine speed control strategy and the engine target speed are determined according to the low slip wear requirements, according to the requirements of ride comfort, the clutch engagement speed and synchronous compensation torque are determined, and an optimal starting control method with zero synchronous shock based on torque compensation is proposed. Based on this, the optimal starting controller with three control loops is designed in Chapter 4, it realizes the functions of closed-loop control of driver torque demand, closed-loop control of sliding impact degree, closed-loop control of zero synchronous impact, and closed-loop control of engine speed with low sliding power. Finally, the vehicle test and simulation verification in Chapter 5 confirms that the control method proposed in this paper can effectively meet the starting control goal and eliminate the synchronization shock simply and efficiently.

Liver steatosis could affect the accuracy of FibroScan in patients with chronic hepatitis B (CHB) and nonalcoholic fatty liver disease (NAFLD). This study aimed to assess the accuracy and cut-off values of FibroScan for diagnosing liver fibrosis and cirrhosis in patients with concomitant CHB and NAFLD. A total of 116 patients with concomitant CHB and NAFLD who underwent FibroScan test and liver biopsy were retrospectively enrolled. Liver fibrosis was staged according to the METAVIR scoring system. Calculations of the areas under receiver-operating characteristic curves (AUROC) were performed and compared for the staging of liver fibrosis. The AUROCs for FibroScan, gamma-glutamyl transpeptidase to platelet ratio (GPR), aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on 4 factors (FIB-4), and NAFLD Fibrosis Score (NFS) were 0.87, 0.73, 0.69, 0.57, and 0.57 for the diagnosis of significant liver fibrosis (METAVIR ≥ F2); 0.89, 0.77, 0.75, 0.68, and 0.60 for severe liver fibrosis (METAVIR ≥ F3); and 0.94, 0.86, 0.80, 0.74, and 0.63 for cirrhosis (F4), respectively. The cutoff values of FibroScan for staging liver fibrosis with sensitivity at least 90% were: 8.0 kPa for significant liver fibrosis, and 10.5 kPa for cirrhosis. The cutoff values of FibroScan for staging liver fibrosis with specificity at least 90% were: 10.8 kPa for significant liver fibrosis, and 17.8 kPa for cirrhosis. FibroScan provides high value for the diagnosis of liver fibrosis and cirrhosis in patients with concomitant CHB and NAFLD.

Significant liver inflammation might be found in 20–34% of chronic hepatitis B virus (HBV) infection patients with detectable HBV DNA and persistently normal alanine transaminase (ALT) (PNALT). We aimed to develop a diagnostic algorithm to predict significant liver inflammation in these specific patients. Using liver biopsy as the gold standard, we developed a novel, simple diagnostic algorithm to predict significant liver inflammation in a training set of 365 chronic HBV infection patients with detectable HBV DNA and PNALT, and validated the diagnostic accuracy in a validation set of 164 similar patients. The novel algorithm (AAGP) attributed to age, ALT, gamma-glutamyl transpeptidase (GGT), and platelet count was developed. In the training set, the area under the receiver operating characteristic curve (AUROC) of AAGP was higher than that of ALT and aspartate transaminase (AST), to diagnose significant liver inflammation (0.77, 0.67, and 0.59, respectively, p p

Tumor multidrug resistance (MDR) is a fatal obstacle to cancer chemotherapy. The combination of P-glycoprotein (P-gp) inhibitor and chemotherapeutic drugs is one of the effective strategies to reverse tumor MDR. Herein, a folate-decorated PCL-ss-PEG-ss-PCL based redox-responsive polymersome (FA-TQR-Co-PS) was constructed, which was loaded with P-gp inhibitor tariquidar (TQR), anticancer drugs doxorubicin (DOX) and paclitaxel (PTX). The results suggested that the FA-TQR-Co-PS with an apparent bilayered lamellar structure displayed good monodispersity, high drug loading capacity, superior stability and redox-stimulated drug release peculiarity. In vitro cellular uptake study demonstrated that FA-TQR-Co-PS increased drug accumulation into MCF-7/ADR cells via the TQR-induced P-gp efflux inhibition, and further improved targeting to tumor cells due to folate receptor-mediated endocytosis. Furthermore, the DOX and PTX cytotoxicity and proapoptotic activity against MCF-7/ADR was enhanced dramatically along with the administration of TQR, and the cell cycle was profoundly blocked in G2/M phase. The folate-targeted redox-responsive polymersomes loaded with chemotherapeutic drugs and P-gp inhibitor demonstrated noticeable synergistic effect against human MDR MCF-7 cells and successfully reversed drug resistance, which displayed high potential in overcoming tumor MDR as a novel drug delivery system.

The combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed new pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs exhibited nano-sized structure (∼100 nm) with good monodispersity, high encapsulation efficiency of both ICG and DOX, triggered DOX release in response to acid pH and reduction environment, and excellent temperature conversion with laser irradiation. In vitro cellular uptake study indicated FA Co-PMs achieved significant targeting to BEL-7404 cells via folate receptor-mediated endocytosis, and laser-induced hyperthermia further enhanced drug accumulation into cancer cells. In vivo biodistribution study indicated that FA Co-PMs prolonged drug circulation and enhanced drug accumulation into the tumor via EPR effect and FA targeting. Furthermore, the ICG-based photo-triggered hyperthermia combined with DOX-based chemotherapy synergistically induced the BEL-7404 cell death and apoptosis, and efficiently suppressed the BEL-7404 xenografted tumor growth while significantly reduced systemic toxicity in vivo. Therefore, the designed dual-responsive Co-PMs were promising theranostic nanocarriers for versatile antitumor drug delivery and imaging-guided cancer chemo-photothermal combination therapy. Statement of Significance The combination of chemotherapy and photothermal therapy in multifunctional nanovesicles has emerged as a promising strategy to improve cancer therapeutic efficacy. Herein, we designed novel pH/reduction dual-responsive and folate decorated polymeric micelles (FA Co-PMs) as theranostic nanocarrier to co-encapsulate doxorubicin (DOX) and indocyanine green (ICG) for targeted NIR imaging and chemo-photothermal combination therapy. The Co-PMs triggered DOX release in response to acid pH and reduction environment and exhibited excellent temperature conversion with laser irradiation. The results indicated FA Co-PMs achieved significant targeting to BEL-7404 cells in vitro and efficiently suppressed the BEL-7404 xenografted tumor growth while significantly reduced systemic toxicity in vivo. Therefore, the designed dual-responsive Co-PMs displayed great potential in imaging-guided cancer chemo-photothermal combination therapy as theranostic nanocarriers.

This study aimed to explore the long-term vegetation cover change and its driving factors in the typical watershed of the Yellow River Basin. This research was based on the Google Earth Engine (GEE), a remote sensing cloud platform, and used the Landsat surface reflectance datasets and the Pearson correlation method to analyze the vegetation conditions in the areas above Xianyang on the Wei River and above Zhangjiashan on the Jing River. Random forest and decision tree models were used to analyze the effects of various climatic factors (precipitation, temperature, soil moisture, evapotranspiration, and drought index) on NDVI (normalized difference vegetation index). Then, based on the residual analysis method, the effects of human activities on NDVI were explored. The results showed that: (1) From 1987 to 2018, the NDVI of the two watersheds showed an increasing trend, in particular, after 2008, the average increase rate of NDVI in the growing season (April to September) increased from 0.0032/a and 0.003/a in the base period (1987–2008) to 0.0172/a and 0.01/a in the measurement period (2008–2018), for the Wei and Jing basins, respectively. In addition, the NDVI significantly increased from 21.78% and 31.32% in the baseline period (1987–2008) to 83.76% and 92.40% in the measurement period (2008–2018), respectively. (2) The random forest and classification and regression tree model (CART) can assess the contribution and sensitivity of various climate factors to NDVI. Precipitation, soil moisture, and temperature were found to be the three main factors that affect the NDVI of the study area, and their contributions were 37.05%, 26.42%, and 15.72%, respectively. The changes in precipitation and soil moisture in the entire Jing River Basin and the upper and middle reaches of the Wei River above Xianyang caused significant changes in NDVI. Furthermore, changes in precipitation and temperature led to significant changes in NDVI in the lower reaches of the Wei River. (3) The impact of human activities in the Wei and Jing basins on NDVI has gradually changed from negative to positive, which is mainly due to the implementation of soil and water conservation measures. The proportions of areas with positive effects of human activities were 80.88% and 81.95%, of which the proportions of areas with significant positive effects were 11.63% and 7.76%, respectively. These are mainly distributed in the upper reaches of the Wei River and the western and eastern regions of the Jing River. These areas are the key areas where soil and water conservation measures have been implemented in recent years, and the corresponding land use has transformed from cultivated land to forest and grassland. The negative effects accounted for 1.66% and 0.10% of the area, respectively, and were mainly caused by urban expansion and coal mining.

In recent years, global reanalysis weather data has been widely used in hydrological modeling around the world, but the results of simulations vary greatly. To consider the applicability of Climate Forecast System Reanalysis (CFSR) data in the hydrologic simulation of watersheds, the Bahe River Basin was used as a case study. Two types of weather data (conventional weather data and CFSR weather data) were considered to establish a Soil and Water Assessment Tool (SWAT) model, which was used to simulate runoff from 2001 to 2012 in the basin at annual and monthly scales. The effect of both datasets on the simulation was assessed using regression analysis, Nash-Sutcliffe Efficiency (NSE), and Percent Bias (PBIAS). A CFSR weather data correction method was proposed. The main results were as follows. (1) The CFSR climate data was applicable for hydrologic simulation in the Bahe River Basin (R 2 of the simulated results above 0.50, NSE above 0.33, and |PBIAS| below 14.8. Although the quality of the CFSR weather data is not perfect, it achieved a satisfactory hydrological simulation after rainfall data correction. (2) The simulated streamflow using the CFSR data was higher than the observed streamflow, which was likely because the estimation of daily rainfall data by CFSR weather data resulted in more rainy days and stronger rainfall intensity than was actually observed. Therefore, the data simulated a higher base flow and flood peak discharge in terms of the water balance, except for some individual years. (3) The relation between the CFSR rainfall data (x) and the observed rainfall data (y) could be represented by a power exponent equation: y=1.4789x 0.8875 (R 2=0.98, P

Significant liver histological changes (SLHC) were defined as moderate to severe liver inflammation (A2 or higher) and/or fibrosis (F2 or higher) using the METAVIR scoring system. This study aimed to develop an algorithm for the non-invasive detection of SLHC in patients with chronic hepatitis B (CHB) and normal or mildly elevated alanine transaminase (ALT) levels. Using liver histology as gold standard, we developed a simple algorithm for the diagnosis of SLHC in a training set (504 patients), and then validated the diagnostic accuracy in a validation set (166 patients). A new algorithm (AAG) attributed to age, ALT, and gamma-glutamyl transpeptidase (GGT) was developed. In the training set, the area under ROC curve (AUROC) of AAG was significantly higher than that of ALT, aspartate transaminase (AST), GPR, and APRI for the diagnosis of SLHC (0.74, 0.68, 0.65, 0.56, and 0.53, respectively; all P

Among approaches of current cancer immunotherapy, a dendritic cell (DC)-targeted vaccine based on nanotechnology could be a promising way to efficiently induce potent immune responses. To enhance DC targeting and vaccine efficiency, we included imiquimod (IMQ), a toll-like receptor 7/8 (TLR 7/8) agonist, and monophosphoryl lipid A (MPLA), a TLR4 agonist, to synthesize lipid-polymer hybrid nanoparticles using PCL-PEG-PCL and DOTAP (IMNPs) as well as DSPE-PEG-mannose (MAN-IMNPS). The spatiotemporal delivery of MPLA (within the outer lipid layer) to extracellular TLR4 and IMQ (in the hydrophobic core of NPs) to intracellular TLR7/8 can activate DCs synergistically to improve vaccine efficacy. Ovalbumin (OVA) as a model antigen was readily absorbed by positively charged DOTAP and showed a quick release in vitro. Our results demonstrated that this novel nanovaccine enhanced cellular uptake, cytokine production, and maturation of DCs. Compared with the quick metabolism of free OVA-agonists, the depot effect of OVA-IMNPs was observed, whereas MAN-OVA-IMNPs promoted trafficking to secondary lymphoid organs. After immunization with a subcutaneous injection, the nanovaccine, especially MAN-OVA-IMNPs, induced more antigen-specific CD8+ T cells, greater lymphocyte activation, stronger cross-presentation, and more generation of memory T cells, antibody, IFN-γ, and granzyme B. Prophylactic vaccination of MAN-OVA-IMNPs significantly delayed tumor development and prolonged the survival in mice. The therapeutic tumor challenge indicated that MAN-OVA-IMNPs prohibited tumor progression more efficiently than other formulations, and the combination with an immune checkpoint blockade further enhanced antitumor effects. Hence, the DC-targeted vaccine codelivery with IMQ and MPLA adjuvants by hybrid cationic nanoparticles in a spatiotemporal manner is a promising multifunctional antigen delivery system in cancer immunotherapy.

Precipitation and human activities are two essential forcing dynamics that influence hydrological processes. Previous research has paid more attention to either climate and streamflow or vegetation cover and streamflow, but rarely do studies focus on the impact of climate and human activities on streamflow and sediment. To investigate those impacts, the Zuli River Basin (ZRB), a typical tributary basin of the Yellow River in China, was chosen to identify the impact of precipitation and human activities on runoff and sediment discharge. A double mass curve (DMC) analysis and test methods, including accumulated variance analysis, sequential cluster, Lee-Heghnian, and moving t-test methods, were utilized to determine the abrupt change points based on data from 1956 to 2015. Correlation formulas and multiple regression methods were used to calculate the runoff and sediment discharge reduction effects of soil conservation measures and to estimate the contribution rate of precipitation and soil conservation measures to runoff and sediment discharge. Our results show that the runoff reduction effect of soil conservation measures (45%) is greater than the sediment discharge reduction effect (32%). Soil conservation measures were the main factor controlling the 74.5% and 75.0% decrease in runoff and sediment discharge, respectively. Additionally, the contribution rate of vegetation measures was higher than that of engineering measures. This study provides scientific strategies for water resource management and soil conservation planning at catchment scale to face future hydrological variability.

Exploiting Toll-like receptor (TLR) agonists or their certain combinations can enhance the immune potency of subunit vaccine. Nevertheless, the design of co-delivery systems which can act in a synergistic and spatio-temporal way to achieve effective and durable specific immune response is still challenging. Here we fabricated mannose-functionalized lipid-hybrid polymersomes (MAN-IMO-PS) for co-delivery of ovalbumin antigen both inside the inner core and outside the lipid layer, TLR7/8 agonist imiquimod within the hydrophobic membrane, TLR4 agonist monophosphoryl lipid A in the lipid layer as programmed nanovaccine to synergistically activate immune responses for improving vaccine efficacy. After efficiently internalized by dendritic cells via mannose targeting and TLR4 ligating, MAN-IMO-PS significantly enhanced cross-presentation and cytokine production. In addition, MAN-IMO-PS showed depot effect at the injection site and enhanced migration to draining lymph nodes. Mice immunized with MAN-IMO-PS elicited greater lymphocyte activation, CD4+ and CD8+ T cell response, effector cytokines secretion, and induced Th-1 biased humoral responses. More importantly, prophylactic vaccination by MAN-IMO-PS significantly delayed tumor occurrence, suppressed tumor growth with prolonged survival, and achieved long-term immune effect. The present study demonstrates a rationally designed nanovaccine for combining antigen, different TLR agonists, and targeting moiety in a programmed manner to induce synergistic antitumor immune response.

Several uncertain factors, such as the protection and circuit breaker refusing operation and misoperation, make it difficult to obtain accurate results based on a single fault location using the switching quantity. So this study proposes a power grid fault location method via multi-data source information fusion. The compressed sensing algorithm is used to reconstruct the electrical signal twice, and the rough fault range and electrical quantity fault degree are obtained respectively. Subsequently, the Bayesian network is used to obtain the switching fault degree of each element in the rough fault range. Finally, DS evidence theory fuses these two fault degrees to obtain the location result. PSCAD software builds an IEEE 14 node system, and the effectiveness of the proposed method is verified by simulation. Furthermore, it can quickly and accurately locate the fault after its occurrence and has good application prospects with respect to the fault location of a low-resistance grounded distribution network.