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Abstract Purpose To compare the performance of Neutrophil-to-Lymphocyte Ratio (NLR) with that of Platelet-to-Lymphocyte Ratio (PLR) in diagnosing neonatal sepsis (NS). Methods PubMed and Embase were searched for relevant studies from the inception of the databases to May, 2022. The pooled sensitivity (SEN), specificity (SPE), and area under the receiver operator characteristic curve (AUC) were measured. Results Thirteen studies involving 2610 participants were included. The SEN, SPE, and AUC of NLR were 0.76 (95%CI: 0.61–0.87), 0.82 (95%CI: 0.68–0.91), and 0.86 (95%CI: 0.83–0.89), respectively, and those of PLR were 0.82 (95%CI: 0.63–0.92), 0.80 (95%CI: 0.24–0.98), and 0.87 (95%CI: 0.83–0.89), respectively. Significant heterogeneity was observed among the studies. Subgroup analysis and meta-regression showed that types of sepsis (p = 0.01 for SEN), gold standard (p = 0.03 for SPE), and pre-set threshold (p

Abstract The Foyemiaowan-Xindiantai cemetery, with more than 10,000 tombs, is located in north-west Gansu Province. The cemetery was active during the Sixteen-State Period of the Western Jin Dynasty (265–439 CE). As the largest ancient tomb group in the Dunhuang region, its cultural core is still mainly based on the cultural tradition of the Central Plains. Metal objects were texturally and chemically analyzed by optical microscopy (OM), scanning electron microscopy coupled with energy-dispersive spectrometry (SEM–EDS), and Raman spectroscopy. The analysis of 36 copper-based objects showed that the main alloying elements were tin and lead, while three objects were brass, with copper and zinc as the main elements. These three pieces of brass are the earliest brass objects found in Gansu Province. The brass contains numerous sulfide inclusions, indicating that the raw materials used to make these objects contained a large amount of residual sphalerite instead of being “pure” calamine. They were then hot forged directly from the original smelted brass, without having been remelted. Brass may have reached China during the Wei Jin Southern and Northern Dynasties (220–589 CE), but it was not widely used in China before the Ming Dynasty (1368–1644 CE). According to the statistics and relevant studies of brass unearthed before the Ming Dynasty in China, although the distribution of brass objects spans a considerable period, it concentrates in three areas from the early to the late stage, showing phased development characteristics. This includes accidental smelting in the Central Plains and Haidai areas, followed by external introduction in the northwest, and the emergence of local production in northeast China. Most brass objects contain lead and tin, which requires further exploration.

Background: In a previous study, we found that traditional Chinese medicine (TCM) alleviated the clinical symptoms and improved the quality of life (QoL) in patients with hepatocellular carcinoma (HCC). Objectives: A cohort was continuously followed up to determine the impact of the TCM adjuvant therapies on the prognosis of HCC after conventional treatments. Methods: We did a retrospective monocentric cohort study including 175 eligible patients. The participants who received TCM adjuvant therapies were termed as TCM group. For the purpose of stratification analysis, the patients who received TCM adjuvant therapies over 3 months per year were further classified into the high frequency group, while the rest of the TCM users were classified into the low frequency group. Non-users were recorded as the control group. The primary outcome was overall survival (OS) and the secondary outcome was the mean progression-free survival (mPFS) primarily introduced in this study, referring to the time from initial diagnosis to the latest progression over the number of disease progressions. Analyses used Cox proportional hazards and Kaplan-Meier (K-M) methods, adjusted for stratification factors. Results: Until June 30, 2021, 56 patients survived, 21 patients were lost to follow-up, and 98 patients died from the disease. Each disease progression of every individual was recorded, and most of the PFS was within 1 year. The baseline data of the allocated groups were balanced, the result revealed that TCM adjuvant therapies might have little influence on OS ( P = .129). However, the 1, 3, and 5-year progression-free survival rates of the patients in TCM and control group were 68.75%, 37.50%; 25.00%, 8.33% and 8.33%, 2.08%, respectively, indicating TCM use significantly extended the mPFS, and decreased the risk of disease progression by a factor of 0.676 ( P = .006). In the patients with BCLC stage B HCC, compared with controls, a 37-month median OS advantage in the high frequency group was noted ( P = .045); and the high frequency of TCM use significantly suppressed disease progression ( P = .001). Conclusions: The present study revealed that TCM adjuvant therapies could postpone disease progression in HCC. Furthermore, using TCM over 3 months per year might extend OS in patients with intermediate HCC.

Hepatocellular Carcinoma (HCC) is one of the most common malignant tumors in the world. Although the current treatment methods for HCC are gradually increasing, its efficacy still cannot meet the medical needs of patients with liver cancer, and new and effective treatment strategies are urgently needed. The total flavonoids of Oldenlandia diffusa (FOD) are the main active components in Oldenlandia diffusa, which have anti-inflammatory, antioxidant and anti-tumor effects, but their mechanism of action in liver cancer is unclear. In this study, we examined the effect of FOD on HCC. Using both in vitro and in vivo models, we confirmed that FOD inhibited HCC proliferation and induced apoptosis and autophagy. Mechanistic studies have shown that FOD induces apoptosis and activates autophagy in HCC cells by inducing endoplasmic reticulum stress (ER stress) and activating the PERK-eIF2α-ATF4 signaling pathway. Taken together, our results suggest that FOD is a potential anticancer drug targeting ER stress for the treatment of HCC.

Ruangan granules (RGGs) have been used to treat liver fibrosis with good clinical efficacy for many years. However, the potential mechanism of action of RGGs against liver fibrosis is still unclear. In this study, we evaluated the quality and safety of this preparation and aimed to explore the anti-liver fibrosis activity and potential mode of action of RGGs using network pharmacology and metabolomics. The results showed that RGGs contained abundant ferulic acid, salvianolic acid B and paeoniflorin, and at the given contents and doses, RGGs were safe and presented anti-liver fibrosis activity. They presented anti-liver fibrosis activity by improving liver function (ALT and AST, p < 0.01) and pathology and decreasing fibrosis markers in the serum of rats caused by CCl4, including HA, LN, PC III, HYP, CoII-V, and α-SMA, and the oxidant stress and inflammatory response were also alleviated in a dose-dependent manner, especially for high-dose RGGs (p < 0.01). Further studies showed that RGGs inhibited the activation of the PI3K-Akt signaling pathway in rats induced by CCl4, regulated pyrimidine metabolism, improved oxidative stress and the inflammatory response by regulating mitochondrial morphology, and alleviated liver fibrosis. Luteolin, quercetin, morin and kaempferol were active compounds and presented the cytotoxicity toward to LX-02 cells. This study provides an overall view of the mechanism underlying the action of RGGs protecting against liver fibrosis.

Two main challenges exist in enhancing oil recovery rate from tight oil reservoirs, namely how to create an effective complicated fracture network and how to enhance the imbibition effect of fracturing fluid. In response to the challenges, through modeling experiment in laboratory and evaluation of field application results, a set of integrated efficient fracturing and enhanced oil recovery (EOR) techniques suitable for tight oil development in China has been proposed. (1) Fracturing with temporary plugging agents to realize stimulation in multiple clusters, to form dense fracture network, and thus maximizing the drainage area; (2) Supporting induced fractures with micro-sized proppants during the prepad fluid fracture-making stage, to generate dense fracture network with high conductivity; (3) Using the liquid nanofluid as a fracturing fluid additive to increase oil-water displacement ratio and take advantage of the massive injected fracturing fluid and maximize the oil production after hydraulic fracturing. Key words: tight oil, hydraulic fracturing, imbibition recovery, temporary plugging agent, micro-sized proppant, nanofluid, surfactant, enhanced oil recovery

Electroconductive hydrogels (EHs) are promising composite biomaterials of hydrogels and conductive electroactive polymers, incorporating bionic physicochemical properties of hydrogels and conductivity, electrochemistry, and electrical stimulation (ES) responsiveness of conductive electroactive polymers. The biomedical domain has increasingly seen EHs’ application to imitating the biological and electrical properties of human tissues, acclaimed as one of the most effective biomaterials. Bone’s complex bioelectrochemical properties and the corresponding stem cell differentiation affected by electrical signal elevate EHs’ application value in repairing and treating bone, cartilage, and skeletal muscle. Noteworthily, the latest orthopedic biological applications require broader information of EHs. Except for presenting the classification and synthesis of EHs, this review recapitulates the advance of EHs application to orthopedics in the past five years and discusses the pertinent development tendency and challenge, aiming to provide a reference for EHs application direction and prospect in orthopedic therapy.

This study reports fabrication, mechanical characterization, and finite element modeling of a novel lattice structure based bimetallic composite comprising 316L stainless steel and a functional dissolvable aluminum alloy. A net-shaped 316L stainless steel lattice structure composed of diamond unit cells was fabricated by selective laser melting (SLM). The cavities in the lattice structure were then filled through vacuum-assisted melt infiltration to form the bimetallic composite. The bulk aluminum sample was also cast using the same casting parameters for comparison. The compressive and tensile behavior of 316L stainless steel lattice, bulk dissolvable aluminum, and 316L stainless steel/dissolvable aluminum bimetallic composite is studied. Comparison between experimental, finite element analysis (FEA), and digital image correlation (DIC) results are also investigated in this study. There is no notable difference in the tensile behavior of the lattice and bimetallic composite because of the weak bonding in the interface between the two constituents of the bimetallic composite, limiting load transfer from the 316L stainless steel lattice to the dissolvable aluminum matrix. However, the aluminum matrix is vital in the compressive behavior of the bimetallic composite. The dissolvable aluminum showed higher Young’s modulus, yield stress, and ultimate stress than the lattice and composite in both tension and compression tests, but much less elongation. Moreover, FEA and DIC have been demonstrated to be effective and efficient methods to simulate, analyze, and verify the experimental results through juxtaposing curves on the plots and comparing strains of critical points by checking contour plots.

Vaccines still are an important way to prevent and treat acquired immunodeficiency syndrome (AIDS). For developing an effective T cell-based AIDS vaccine, it is critical to define the human leukocyte antigen (HLA) type and epitope that elicit the most potent responses. This study involved 29 antiretroviral therapy-naive and chronic human immunodeficiency virus (HIV)-1 subtype B-infected individuals. A polymerase chain reaction-sequence-specific primer was used to detect the HLA typing, and the enzyme-linked immunospot assay to quantify the T-cell immune function. The results showed that the HLA-DQB1*06-positive group had higher CD4 counts and lower viral load (VL) compared with the HLA-DQB1*06-negative group; A higher magnitude of HIV-1-specific T-cell response and breadth were observed in the HLA-DQB1*06-positive group; the T-cell response was proportional to VL (R2 = 0.488, P = 0.0368) in the HLA-DQB1*06-positive group. The total T-cell responses to HIV-1 Nef core region were quantified at the single-peptide level. Nine (90%) peptides were recognized in 18 (62.1%) individuals. The breath of Nef core region-specific T-cell response was correlated positively with CD4+ T cell count and inversely with VL, which improved disease outcomes. These data revealed that HLA-DQB1*06 had a protective effect on the course of HIV-1 and T-cell targeting of certain specific Nef epitopes, contributing to HIV-1 suppression. The results suggested the potential use of HLA-DQB1*06 and Nef core region in HIV-1 T-cell vaccine design.

Abstract Exosomes are emerging as a new type of cancer biomarkers. Exosome is a bilayered nano-sized vesicle secreted by various living cells in all body fluids. Based on the expanding albeit incomplete knowledge of their biogenesis, secretion by cells and cancer cell-specific molecular and genetic contents, exosomes are viewed as promising, clinically-relevant surrogates of cancer progression and response to therapy. Preliminary proteomic, genetic and functional profiling of cancer cell-derived or cancer plasma-derived exosomes confirms their unique characteristics. Alterations in protein or nucleic acid profiles of exosomes in plasma correlate with pathological processes of many diseases including cancer. However, previous studies on exosome application in cancer diagnosis and treatment mainly focussed on miRNAs. With the development of rapid large-scale production, purification, extraction and screening of exosomal contents, exosomal protein application can be explored for early stage cancer diagnosis, monitoring and prognosis evaluation. Here, we summarized the recent developments in application of exosomal proteins for cancer diagnosis.

Additive manufacturing (AM) enables the production of complex structured parts with tailored properties. Instead of manufacturing parts as fully solid, they can be infilled with lattice structures to optimize mechanical, thermal, and other functional properties. A lattice structure is formed by the repetition of a particular unit cell based on a defined pattern. The unit cell’s geometry, relative density, and size dictate the lattice structure’s properties. Where certain domains of the part require denser infill compared to other domains, the functionally graded lattice structure allows for further part optimization. This manuscript consists of two main sections. In the first section, we discussed the dual graded lattice structure (DGLS) generation framework. This framework can grade both the size and the relative density or porosity of standard and custom unit cells simultaneously as a function of the structure spatial coordinates. Popular benchmark parts from different fields were used to test the framework’s efficiency against different unit cell types and grading equations. In the second part, we investigated the effect of lattice structure dual grading on mechanical properties. It was found that combining both relative density and size grading fine-tunes the compressive strength, modulus of elasticity, absorbed energy, and fracture behavior of the lattice structure.

Alzheimer’s disease (AD) remains to be a grand challenge for the international community despite over a century of exploration. A key factor likely accounting for such a situation is the vast heterogeneity in the disease etiology, which involves very complex and divergent pathways. Therefore, intervention strategies shall be tailored for subgroups of AD patients. Both demographic and in-depth information is needed for patient stratification. The demographic information includes primarily APOE genotype, age, gender, education, environmental exposure, life style, and medical history, whereas in-depth information stems from genome sequencing, brain imaging, peripheral biomarkers, and even functional assays on neurons derived from patient-specific induced pluripotent cells (iPSCs). Comprehensive information collection, better understanding of the disease mechanisms, and diversified strategies of drug development would help with more effective intervention in the foreseeable future.

Peripheral blood is an attractive source for the discovery of disease biomarkers. Gene expression profiling of whole blood or its components has been widely conducted for various diseases. However, due to population heterogeneity and the dynamic nature of gene expression, certain biomarkers discovered from blood transcriptome studies could not be replicated in independent studies. In the meantime, it's also important to know whether a reliable biomarker is shared by several diseases or specific to certain health conditions. We hypothesized that common mechanism of immune response in blood may be shared by different diseases. Under this hypothesis, we surveyed publicly available transcriptome data on infectious and autoimmune diseases derived from peripheral blood. We examined to which extent common gene dys-regulation existed in different diseases. We also investigated whether the commonly dys-regulated genes could serve as reliable biomarkers. First, we found that a limited number of genes are frequently dys-regulated in infectious and autoimmune diseases, from which we selected 10 genes co-dysregulated in viral infections and another set of 10 genes co-dysregulated in bacterial infections. In addition to its ability to distinguish viral infections from bacterial infections, these 20 genes could assist in disease classification and monitoring of treatment effect for several infectious and autoimmune diseases. In some cases, a single gene is sufficient to serve this purpose. It was interesting that dys-regulation of these 20 genes were also observed in other types of diseases including cancer and stroke where certain genes could also serve as biomarkers for diagnosis or prognosis. Furthermore, we demonstrated that this set of 20 genes could also be used in continuous monitoring of personal health. The rich information from these commonly dys-regulated genes may find its wide application in clinical practice and personal healthcare. More validation studies and in-depth investigations are warranted in the future.

One of the major challenges in the removal of organic pollutants is to design a material with high efficiency and high flux that can remove both cationic and anionic dyes, oil-in-water (O/W) emulsion and heavy metal ions. Herein, we constructed novel chemically stabilized MgAl-layered-double-hydroxide/sepiolite (MgAl-LDH/Sep) composite membranes via 3D hierarchical architecture construction methods. These membranes were analyzed by scanning electron microscopy (SEM), atomic force microscopy (AFM) and X-ray diffraction (XRD), etc. Benefiting from the presence of hydrophilic functional groups on the surface of the film, the membranes show an enhanced water flux (~1200 L·m−2 h−1), while keeping a high dyes rejection (above 99.8% for anionic and cationic dyes). Moreover, the CA membrane coupled with MgAl-LDH/Sep exhibits a multifunctional characteristic for the efficient removal of mesitylene (99.2%), petroleum ether (99.03%), decane (99.07%), kerosene (99.4%) and heavy metal ion in water due to the layer-by-layer sieving. This hierarchical architecture is proved to have excellent environmental and chemical stability. Therefore, the membrane has potential in the treatment of sewage wastewater.

An opened natural fracture (NF) intercepted by a pressurized hydro-fracture (HF) will be diverted in a new direction at the tips of the original NF and subsequently form a complex fracture network. However, a clear understanding of the diversion behavior of fracture networks in tight reservoirs with frictional NFs is lacking. By means of the extended finite element method(XFEM), this study investigates the diversion mechanisms of an opened NF intersected by an HF in naturally fractured reservoirs. The factors affecting the diversion behavior are intensively analyzed, such as the location of the NF, the horizontal principal stress difference, the intersection angle between HF and NF, and the viscosity of the fracturing fluid. The results show that for a constant length of NF (7 m): (1) the upper length of the diverted fracture (DF) decreases by about 2 m with a 2 m increment of the upper length of NF ( L u p p e r ), while the length of DF increases 9.06 m with the fluid viscosity increased by 99 mPa · s; (2) the deflection angle in the upper parts increases by 30.8° with the stress difference increased by 5 MPa, while the deflection angle increases by 61.2° with the intersection angle decreased by 30°. It is easier for the opened NF in lower parts than that in upper parts to be diverted away from its original direction. It finally diverts back to the preferred fracture plane (PFP) direction. The diversion mechanisms of the fracture network are the results of the combined action of all factors. This will provide new insight into the mechanisms of fracture network generation in tight reservoirs with NFs.

Abstract The inflorescences morphology (IM) of sorghum (Sorghum bicolor L. Moench) affects its resistance to pests, diseases, and grain yields. However, the specific genetic factors underlying in IM are not yet fully elucidated. Here we conducted a comprehensive genome-wide association analysis (GWAS) to identify the stable and adaptive Quantitative Trait Loci (QTL) for five IM traits (panicle length, the number of cob nodes, the number of primary branches, the largest length of the primary branch, and panicle type) in a sorghum panel, which adapted to different environments from the south to north in China. Totally, 2,015,850 high quality single nucleotide polymorphisms (SNPs) were obtained. Population structure analysis showed that two distinct genetic sub-populations were divided according to their geographic origin. Seventy-one QTLs distributed in 41 genetic regions on 9 chromosomes were identified. These regions harbored 21 high-confident candidate genes that were homologous to rice domestication genes, including 7 related to IM. Two domestication-related genes (Sobic.003G052700 and Sobic.006G247700) were located into two major QTL regions (QTL3.4721839 and QTL6.58709500) which were identified in multi-environments. Allelic variations in the two genes displayed a geographical pattern, indicating that different IM traits were selected by south and north sorghum breeders, such as south sorghums had long and loose panicles in order to adapt the hot and humid climate, while north sorghums had short and compact panicle to increase planting density and grain yield per unit area due to dry climate. This work provides new breeding strategies and resources for developing locally adapted sorghum varieties.