Correlation of HBV Core-Related Antigen with Conventional Serologic Indicators of Hepatitis B and Disease Stage.

BACKGROUND: Hepatitis B caused by hepatitis B virus (HBV) infection is a serious global public health issue. Currently, serological indicators serve as important markers for the diagnosis of hepatitis B. It has been found that HBV core-related antigen (HBcrAg) correlates well with intrahepatic cccDNA, intrahepatic HBV DNA, serum HBV DNA, and hepatitis B e antigen (HBeAg). To provide a more reliable basis for the diagnosis and treatment of hepatitis B, we explored the correlation between HBcrAg and conventional serologic testing indicators and disease staging. METHODS: Five hundred forty-two patient serum samples were collected at the First Affiliated Hospital of Soochow University from November 2021 to March 2022. The serum HBcrAg was measured by the magnetic particle chemiluminescence method in addition with other serum indicators. RESULTS: HBcrAg statistically correlated with HBV DNA level (r = 0.655, p < 0.001) and HBeAg level (r = 0.945, p < 0.001. The mean HBcrAg levels in the immune-tolerant and immune-clearance phases were significantly higher than those in the immunologic-control phase and the reactivation phase. This study demonstrated that serum HBcrAg positively correlated with serum HBV DNA and HBeAg. Even in cases where HBV DNA and HBeAg are negative, there is still a higher positivity rate of HBcrAg in hepatitis B patients. CONCLUSIONS: HBcrAg is a reliable serum marker to avoid underdiagnosis of occult HBV infection.

Engineering Fatty Acid Biosynthesis in Microalgae: Recent Progress and Perspectives.

Microalgal lipids hold significant potential for the production of biodiesel and dietary supplements. To enhance their cost-effectiveness and commercial competitiveness, it is imperative to improve microalgal lipid productivity. Metabolic engineering that targets the key enzymes of the fatty acid synthesis pathway, along with transcription factor engineering, are effective strategies for improving lipid productivity in microalgae. This review provides a summary of the advancements made in the past 5 years in engineering the fatty acid biosynthetic pathway in eukaryotic microalgae. Furthermore, this review offers insights into transcriptional regulatory mechanisms and transcription factor engineering aimed at enhancing lipid production in eukaryotic microalgae. Finally, the review discusses the challenges and future perspectives associated with utilizing microalgae for the efficient production of lipids.

Temperature-dependent resistance of carbon nanotube fibers.

Carbon nanotube fibers are highly recommended in the field of temperature sensor application owing to their excellent electrical conductivity and thermal conductivity. Here, this work demonstrated the rapid thermal response behaviour of CNT fibers fabricated by floating catalyst CVD method, which was measured by anin situtechnique based on the CNT film electric heater with excellent electrothermal response properties. The temperature dependences of resistance and structure were both explored. Experimental investigation indicates that the reduction in the inter-CNT interspace in the fibers caused by thermally driven actuation was dominantly responsible for the decrease of the fibers resistance during the heating process. Especially, the heated fibers showed 7.2% decrease in electrical resistance at the applied square-wave voltage of 8 V, and good temperature sensitivity (-0.15% °C-1). The as-prepared CNT fibers also featured a rapid and reversible electrical resistance response behaviour when exposed to external heating stimulation. Additionally, with the increment of temperature and twist-degree, the generated contraction actuation increased, which endowed the CNT fibers with more decrease in electrical resistance. These observations further suggested that the temperature-dependent conduction behavior of the CNT fibers with a high reversibility and repeatability was strongly correlated with their structure response to heat stimulation. As a consequence, the temperature-conduction behavior described here may be applied in other CNT-structured fibers and facilitated the improvement in their temperature-sensing applications.

Electronic Structure Tuning of 2D Metal (Hydr)oxides Nanosheets for Electrocatalysis.

2D metal (hydr)oxide nanosheets have captured increasing interest in electrocatalytic applications aroused by their high specific surface areas, enriched chemically active sites, tunable physiochemical properties, etc. In particular, the electrocatalytic reactivities of materials greatly rely on their surface electronic structures. Generally speaking, the electronic structures of catalysts can be well adjusted via controlling their morphologies, defects, and heterostructures. In this Review, the latest advances in 2D metal (hydr)oxide nanosheets are first reviewed, including the applications in electrocatalysis for the hydrogen evolution reaction, oxygen reduction reaction, and oxygen evolution reaction. Then, the electronic structure-property relationships of 2D metal (hydr)oxide nanosheets are discussed to draw a picture of enhancing the electrocatalysis performances through a series of electronic structure tuning strategies. Finally, perspectives on the current challenges and the trends for the future design of 2D metal (hydr)oxide electrocatalysts with prominent catalytic activity are outlined. It is expected that this Review can shed some light on the design of next generation electrocatalysts.

Interface-engineered Co3S4/CoMo2S4nanosheets as efficient bifunctional electrocatalysts for alkaline overall water splitting.

Exploring bifunctional electrocatalysts with high efficiency, inexpensive, and easy integration is still the daunt challenge for the production of hydrogen on a large scale by means of water electrolysis. In this work, a novel free-standing Co3S4/CoMo2S4heterostructure on nickel foam by a facial hydrothermal method is demonstrated to be an effective bifunctional electrocatalyst for overall water splitting (OWS). The synthesized Co3S4/CoMo2S4electrocatalyst achieves ultralow overpotentials of 143 mV@10 mA cm-2for hydrogen evolution reaction (HER) and 221 mV@25 mA cm-2for oxygen evolution reaction (OER), respectively, in 1 M KOH. Moreover, it presents a greatly improved durability and stability under operando electrochemical conditions. When used as catalysts for OWS, the Co3S4/CoMo2S4-3//Co3S4/CoMo2S4-3 electrodes just need 1.514 V to make it to the current density of 10 mA cm-2. It is supposed that the introduction of heterogeneous interface between Co3S4and CoMo2S4could give rise to plentiful active sites and enhanced conductivity, and thus boost excellent catalytic performances. Moreover, the porous feature of free-standing nanosheets on nickel foam could benefits catalytic performances by accelerating charge transport and releasing bubbles rapidly. This work proposes a bifunctional catalyst system with the heterogeneous interface, which could be used in a sustainable green energy system.

18 Additional Amino Acids of the Signal Peptide of the Bombyx mori Nucleopolyhedrovirus GP64 Activates Immunoglobulin Binding Protein (BiP) Expression by RNA-seq Analysis.

GP64 is the key membrane fusion protein of Group I baculovirus, and while the Bombyx mori nucleopolyhedrovirus (BmNPV) GP64 contains a longer n-region (18 amino acid) of the signal peptide than does the Autographa californica multiple nucleopolyhedrovirus (AcMNPV), the function of the n-region has not been determined. In this study, we first showed that n-region is required for membrane protein localization in BmN cells, then the transcriptome sequencing was conducted on proteins guided by different signal peptide regions, and the results were analyzed and validated by quantitative PCR and luciferase assays. The results indicated that 1049 differentially expressed genes (DEGs) were identified among the different region of signal peptides and the control. With the n-region, the protein export pathway was upregulated significantly, the Wnt-1 signaling pathway was downregulated, and BiP was significantly activated by the GP64 full-length signal peptide. Furthermore, RNA interference on BiP efficiently increased luciferase secretion. These results indicate that the GP64 n-region plays a key role in protein expression and regulation.

Effect of the hairpin structure of peptide inhibitors on the blockade of PD-1/PD-L1 axis.

Blockade of the PD-1/PD-L1 axis using antibody drugs has been a clinically efficacious immunotherapy in cancer treatment. However, studies on peptide inhibitors blocking the interaction between PD-1/PD-L1 in cancer treatment in clinical practice have not yet been reported. In this study, a series of peptide inhibitors were synthesized based on a continuous sequence of 14 amino acids from PD-L1 and suitable modifications to form a hairpin structure. The effect of inhibitors on the blockage of PD-1/PD-L1 by increasing the stability of the hairpin structure was determined using BLI and co-culture models. The results showed that increasing the stability of the hairpin improved the affinity of inhibitors to PD-1 and increased IL-2 secretion. Therefore, modifying the hairpin structure of peptide inhibitors may be a useful approach to block the interaction between PD-1 and PD-L1.

Retrospective analysis of HIV-1 drug resistance mutations in Suzhou, China from 2009 to 2014.

In this study, we investigated drug resistance levels in human immunodeficiency virus (HIV)-1-infected patients in Suzhou by retrospectively analyzing this property and the characteristics of circulating HIV-1 strains collected from 2009 to 2014. A total of 261 HIV-1-positive plasma samples, confirmed by the Suzhou CDC, were collected and evaluated to detect HIV-1 drug resistance genotypes using an in-house method. The pol gene fragment was amplified, and its nucleic acid sequence was determined by Sanger sequencing. Drug resistance mutations were then analyzed using the Stanford University HIV resistance database ( https://hivdb.stanford.edu ). A total of 216 pol gene fragments were amplified and sequenced with 16.7% (36/216) of sequences revealing these mutations. The drug resistance rates of protease, nucleoside reverse transcriptase, and non-nucleoside reverse transcriptase inhibitors (NNRTIs) were 4/36 (11.1%), 2/36 (5.6%), and 30/36 (83.3%), respectively. Five surveillance drug resistance mutations were found in 36 sequences, of which, three were found among specimens of men who have sex with men. Potential low-level resistance accounted for 33% of amino acid mutations associated with NNRTIs. Two of the mutations, M230L and L100I, which confer a high level of resistance efavirenz (EFV) and nevirapine (NVP) used as NNRTIs for first-line antiretroviral therapy (ART), were detected in this study. Therefore, when HIV-1 patients in Suzhou are administered fist-line ART, much attention should be paid to the status of these mutations that cause resistance to EVP, EFV, and NVP.

A deuterohemin peptide protects a transgenic Caenorhabditis elegans model of Alzheimer's disease by inhibiting Aß1-42 aggregation.

Alzheimer's disease (AD) is a progressive neurodegenerative brain disease and is the most common cause of dementia in the elderly. The main hallmark of AD is the deposition of insoluble amyloid (Aß) outside the neuron, leading to amyloid plaques and neurofibrillary tangles in the brain. Deuterohemin-Ala-His-Thr-Val-Glu-Lys (DhHP-6), a novel porphyrin-peptide, has both microperoxidase activity and cell permeability. In the present study, DhHP-6 efficiently inhibited the aggregation of Aß and reduced the ß-sheet percentage of Aß from 89.1% to 78.3%. DhHP-6 has a stronger affinity (KD = 100 ±â€¯12 µM) for binding with Aß at Phe4, Arg5, Val18, Glu11 and Glu22. In addition, DhHP-6 (100 µM) significantly prolonged lifespan, alleviated paralysis and reduced Aß plaque formation in the Aß1-42 transgenic Caenorhabditis elegans CL4176 model of AD. Our results demonstrate that DhHP-6 is a potential drug candidate that efficiently protects a transgenic C. elegans model of Alzheimer's disease by inhibiting Aß aggregation.

Drug Delivery System with Multiple Rare Earth Ions Fluorescent-Labeling Drugs and Magnetic Nanoparticles.

The bifunctional drug delivery system combining magnetic nanoparticles and fluorophore possesses the characterization of magnetism and fluorescence. However, the accurate tracing of the drug release and diffusion pathway is affected by the separation of drug and fluorescent molecule. In this paper, we synthesized the fluorescent-labeling drug by covalently binding Aspirin with rare earth ions Terbium (Te) and Gadolinium (Gd), which was incorporated into chitosan microspheres with magnetic nanoparticles Fe3O4 to prepare magnetic and fluorescent drug delivery system. Investigated by Fourier transform infrared spectrometer, fluorescence spectrophotometer, X-ray diffraction, vibrating sample magnetometer, and scanning electron microscopy, the chitosan microspheres showed excellent fluorescent and magnetic properties. Compared with the single rare earth ion complex, the multiple rare earth ions complexes with Aspirin TbxGd1-x(Aspirin)3 · 2H2O (x 0.25, 0.5, 0.75) exhibited superior fluorescent intensity.

Oral DhHP-6 for the Treatment of Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is associated with pancreatic ß-cell dysfunction which can be induced by oxidative stress. Deuterohemin-ßAla-His-Thr-Val-Glu-Lys (DhHP-6) is a microperoxidase mimetic that can scavenge reactive oxygen species (ROS) in vivo. In our previous studies, we demonstrated an increased stability of linear peptides upon their covalent attachment to porphyrins. In this study, we assessed the utility of DhHP-6 as an oral anti-diabetic drug in vitro and in vivo. DhHP-6 showed high resistance to proteolytic degradation in vitro and in vivo. The degraded DhHP-6 product in gastrointestinal (GI) fluid retained the enzymatic activity of DhHP-6, but displayed a higher permeability coefficient. DhHP-6 protected against the cell damage induced by H2O2 and promoted insulin secretion in INS-1 cells. In the T2DM model, DhHP-6 reduced blood glucose levels and facilitated the recovery of blood lipid disorders. DhHP-6 also mitigated both insulin resistance and glucose tolerance. Most importantly, DhHP-6 promoted the recovery of damaged pancreas islets. These findings suggest that DhHP-6 in physiological environments has high stability against enzymatic degradation and maintains enzymatic activity. As DhHP-6 lowered the fasting blood glucose levels of T2DM mice, it thus represents a promising candidate for oral administration and clinical therapy.

La/SSB chimeric autoantibody receptor modified NK92MI cells for targeted therapy of autoimmune disease.

It has been long sought to specifically eliminate B-cell clones that generate autoreactive antibodies, while sparing the immune system when combating autoimmune disease. Although it was impossible to achieve this goal before, newly developed techniques have made it feasible today. Autoantibodies against La/SSB were involved in several autoimmune diseases. Here, we aimed to introduce La/SSB epitope-based chimeric autoantibody receptors (CAAR) into NK92MI cells enabled it to destroy the corresponding La/SSB-specific B cell receptor (BCR) -bearing lymphoma cells (LaA-BCR-Romas, LaA-BCR-Maver-1, and LaA-BCR-Jurkat cells). Such cell lines could eliminate a part of the B-cells in the blood of patients positive for anti-La/SSB antibodies. The CAAR we used in this study was constructed by fusing fragments from the nucleus protein, La/SSB, with the TCR signaling molecules, CD28, CD137, and CD3ζ. Thus, this method could specifically destroy the La/SSB autoreactive B-cell clones. Our results might provide a new strategy to combat antibody-mediated autoimmune diseases.

All-in-One Bifunctional Oxygen Electrode Films for Flexible Zn-Air Batteries.

As a promising energy-storage device, rechargeable Zn-air batteries have attracted considerable interests. Herein, a bifunctional oxygen electrode film prepared by adhering NiCo2 O4 nanosheets to a nitrogen and oxygen dual-doped carbon nanotubes film in a large scale is reported. The resulting self-supporting film electrode is multifunctional, which integrates a porous conducting structure for air diffusion and charge transfer, high-performance catalysts for oxygen reduction and evolution, and novel structural flexibility. The composite film demonstrates excellent oxygen reduction/evolution reaction catalytic activities with low Tafel slopes (50 mV dec-1 for oxygen reduction reaction; 92 mV dec-1 for oxygen evolution reaction). Without any additional current collector, gas diffusion layer, or binder, the obtained bifunctional film performs as an "all-in-one" air electrode in a Zn-air battery. A 50-cm-long cable-shaped Zn-air battery based on such a film air electrode exhibits high operating potentials (≈1.2 V at 0.25 mA cm-2 ), low charging-discharging overpotentials (≈0.7 V), and stable cycling performance. Moreover, the flexible cable Zn-air batteries show excellent stability under different deformation conditions. The proposed concept of constructing scalable, all-in-one, freestanding, and flexible air electrodes would pave the way to develop next-generation wearable and portable energy-storage devices.

Large-Stroke Electrochemical Carbon Nanotube/Graphene Hybrid Yarn Muscles.

Artificial muscles are reported in which reduced graphene oxide (rGO) is trapped in the helical corridors of a carbon nanotube (CNT) yarn. When electrochemically driven in aqueous electrolytes, these coiled CNT/rGO yarn muscles can contract by 8.1%, which is over six times that of the previous results for CNT yarn muscles driven in an inorganic electrolyte (1.3%). They can contract to provide a final stress of over 14 MPa, which is about 40 times that of natural muscles. The hybrid yarn muscle shows a unique catch state, in which 95% of the contraction is retained for 1000 s following charging and subsequent disconnection from the power supply. Hence, they are unlike thermal muscles and natural muscles, which need to consume energy to maintain contraction. Additionally, these muscles can be reversibly cycled while lifting heavy loads.

Development of Magnetic-Fluorescent Bifunctional Drug Delivery System with Dual Drug Content and Enhanced Fluorescence.

The drug delivery system incorporating magnetic particles and fluorescent marker would be uniquely effective for magnetic targeting and fluorescent tracing. In order for the fluorescent signals to reflect the drug delivery accurately, the separation of the fluorescent label and drugs must be counteracted. The objective of the current study was to design a method of binding drugs to the fluorescent material so that the drug diffusion and delivery could be monitored precisely. To obtain fluorescently-labeled drugs, complexes of the rare earth ion with a single drug benzimidazole (Tb(Bim)3), and with combined drugs benzimidazole and aspirin (TbBim(Asp)2) were generated. Subsequently, the magnetic nanoparticles Fe3O4 and TbBim(Asp)2 were encapsulated in chitosan microspheres to prepare magnetic fluorescent bifunctional drug delivery system Fe3O4/TbBim(Asp)2/Chitosan. The intermediate and final products were analyzed by spectroscopy, X-ray diffraction, magnetometry, and electron microscopy, documenting that the newly developed drug-containing nanoparticles exhibited desirable fluorescent, magnetic, and morphologic properties.

Serum Lipase as Clinical Laboratory Index for Chronic Renal Failure Diagnosis.

BACKGROUND: Measuring the level of serum lipase has been used for the clinical diagnosis of acute pancreatitis. Reports showed that the serum lipase level increased in patients of clinical renal failure. In this study, we aimed to measure the change of serum lipase levels in chronic kidney diseases and determine whether it could serve as a clinical laboratory index for clinical renal failure diagnosis. Materials: The OLYMPUS AU5400 automatic biochemical analyzer was used to determine the serum levels of lipase and creatinine. The study included 120 cases in the clinical renal failure group, 76 cases in the nephrotic syndrome group, 81 cases in the chronic nephritis group, and 80 healthy controls from our hospital volunteers in the same period. We then compared the lipase levels and conducted statistical analyses among these groups. RESULTS: The serum lipase levels were 15.3 U/L, 79.8 U/L, 45.1 U/L, and 51.0 U/L in the normal control, clinical renal failure, nephrotic syndrome, and chronic nephritis groups, respectively. The lipase levels in the groups with diseases were significantly different compared with that of the normal control group (p < 0.01). The lipase level of the clinical renal failure group was significantly higher than that of the nephrotic syndrome group and chronic nephritis group (p < 0.01). However, no statistically significant difference between the nephrotic syndrome and chronic nephritis group (p > 0.05) was observed. Moreover, an association of the serum lipase with disease progression was observed in the study. CONCLUSIONS: Serum lipase is an effective serological index which can reflect the clinical changes in the clinical renal failure and tends to increase through the progression of renal dysfunction.

Trends of subtype variation of human immunodeficiency virus type 1 in Zhejiang Province, China.

The epidemic characteristics of human immunodeficiency virus type 1 (HIV-1) in Zhejiang Province have not been systematically identified. This study presented a dynamic analysis of HIV-1 subtype variation in Zhejiang from 2004 to 2008, based on the surveillance of molecular epidemiology or drug resistance. CRF01_AE was the major strain (43.5 %) spreading across the province, second by B/B' (17.9 %), CRF07_BC (17.1 %), and CRF08_BC (13.7 %). The strains were mainly transmitted by heterosexual contact. Novel recombinant strains and vertical transmission were occasionally reported. Floating population from other provinces accounted for a significant number of HIV-1 cases in Zhejiang. These data may provide us rational intervention strategy for further control of HIV dissemination.

Modified minimum principal stress estimation formula based on Hoek-Brown criterion and equivalent Mohr-Coulomb strength parameters.

The most critical parameter for determining equivalent values for the Mohr-Coulomb friction angle and cohesion from the nonlinear Hoek-Brown criterion is the upper limit of confining stress. For rock slopes, this value is the maximum value of the minimum principal stress ([Formula: see text]) on the potential failure surface. The existing problems in the existing research are analyzed and summarized. Using the finite element method (FEM), the location of potential failure surfaces for a wide range of slope geometries and rock mass properties are calculated using the strength reduction method, and a corresponding finite element elastic stress analysis was carried in order to determine [Formula: see text] of the failure surface. Through a systematic analysis of 425 different slopes, it is found that slope angle (ß) and geological strength index (GSI) have the most significant influence on [Formula: see text] while the influence of intact rock strength and the material constant [Formula: see text] are relatively small. According to the variation of [Formula: see text] with different factors, two new formulas for estimating [Formula: see text] are proposed. Finally, the proposed two equations were applied to 31 real case studies to illustrate the applicability and validity.

GRIN2D knockdown suppresses the progression of lung adenocarcinoma by regulating the E2F signalling pathway.

OBJECTIVE: Glutamate ionotropic receptor N-methyl-d-aspartate (NMDA) type subunit 2D (GRIN2D) is a member of the GRIN gene family and contributes to the development and function of the brain. GRIN2D was found to be upregulated in several types of cancers; however, its mechanism in lung adenocarcinoma (LUAD) remains unclear. METHODS: We determined the role of GRIN2D in LUAD. In addition, we investigated the potential mechanism of GRIN2D in LUAD using bioinformatics analysis and confirmed this mechanism using biological approaches. RESULTS: GRIN2D was found to be upregulated in LUAD tissues and cells. GRIN2D knockdown reduced the proliferation and accelerated the apoptosis of LUAD cells. GRIN2D also activated glycolysis, gluconeogenesis, and the E2F signalling pathway in LUAD. GRIN2D knockdown significantly inhibited glucose uptake, lactate production, the ATP/ADP ratio, ECAR, and OCR in LUAD cells. E2F1 overexpression eliminated the inhibitory effect of GRIN2D knockdown in LUAD cells. CONCLUSIONS: GRIN2D knockdown suppresses cell growth, migration, glycolysis, and gluconeogenesis of LUAD by inhibiting the E2F signalling pathway.

Electronic Asymmetry Engineering of Fe-N-C Electrocatalyst via Adjacent Carbon Vacancy for Boosting Oxygen Reduction Reaction.

Single-atomic transition metal-nitrogen-carbon (M-N-C) structures are promising alternatives toward noble-metal-based catalysts for oxygen reduction reaction (ORR) catalysis involved in sustainable energy devices. The symmetrical electronic density distribution of the M─N4 moieties, however, leads to unfavorable intermediate adsorption and sluggish kinetics. Herein, a Fe-N-C catalyst with electronic asymmetry induced by one nearest carbon vacancy adjacent to Fe─N4 is conceptually produced, which induces an optimized d-band center, lowered free energy barrier, and thus superior ORR activity with a half-wave potential (E1/2 ) of 0.934 V in a challenging acidic solution and 0.901 V in an alkaline solution. When assembled as the cathode of a Zinc-air battery (ZAB), a peak power density of 218 mW cm-2 and long-term durability up to 200 h are recorded, 1.5 times higher than the noble metal-based Pt/C+RuO2 catalyst. This work provides a new strategy on developing efficient M-N-C catalysts and offers an opportunity for the real-world application of fuel cells and metal-air batteries.