Study of the Extremely Low-Frequency Noise Characteristics of a Micro-Thrust Measurement Platform.

The critical structural parameters are optimized and studied using the numerical simulation method to improve the resolution and stability of the Micro-Thrust Measurement Platform (MTMP). Under two different ground random vibration environments, the parameters, such as pivot thickness, pendulum rod length, and pivot structure, are focused on analyzing the influence of the system's resolution and stability. The results show that when the thickness of the pivot is 0.04 mm or 0.2 mm, and the pendulum rod length is 2 m, the effect of ground random vibration on the MTMP is minimized. At 0.1 mHz, it can reach 0.0057 µN/Hz. In the series double-pivot structure, an appropriate increase in the distance between the sheets can further optimize the above conclusions. The results and analysis within this study can provide support for the engineering design of the MTMP.

Creatine kinase elevation in chronic hepatitis B patients with telbivudine therapy: influence of telbivudine plasma concentration and single nucleotide polymorphisms of TK2, RRM2B, and NME4.

PURPOSE: To study the correlations of genetic variants of telbivudine phosphorylase kinases and telbivudine plasma concentration with creatine kinase elevation in chronic hepatitis B patients who received telbivudine. METHODS: An observational study was performed in China chronic hepatitis B patients receiving telbivudine therapy at 600 mg once daily. Plasma concentration was measured 12 h after taking telbivudine using ultra-performance liquid chromatography-tandem mass spectrometry and SNPs located in RRM2B, TK2, and NME4 was detected by MALDI-TOF mass spectrometry. All statistical analyses were performed with R 4.3.1 and all graphs were drawn by Origin 2023b and P value < 0.05 was considered statistically significant. RESULTS: A total of 140 patients receiving telbivudine therapy were recruited with a median plasma concentration of 952.49 (781.07-1238.98) ng/mL. The value of plasma concentration was proportional to the grade of creatine kinase elevation and the best telbivudine plasma concentration threshold to discriminate the grade 3/4 CK elevation was 1336.61 ng/mL. Multivariate analysis revealed that plasma concentration and rs3826160 were the independent risk factor of telbivudine-induced creatine kinase elevation. Patients with TC and CC genotype in rs3826160 not only had a higher incidence of creatine kinase elevation but also a higher plasma concentration than TT genotype carriers. CONCLUSION: Chronic hepatitis B patients with TC and CC genotype in rs3826160 have high telbivudine plasma concentration are at risk of elevated creatine kinase.

BTLA contributes to acute-on-chronic liver failure infection and mortality through CD4+ T-cell exhaustion.

B- and T-lymphocyte attenuator (BTLA) levels are increased in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). This condition is characterized by susceptibility to infection and T-cell immune exhaustion. However, whether BTLA can induce T-cell immune exhaustion and increase the risk of infection remains unclear. Here, we report that BTLA levels are significantly increased in the circulating and intrahepatic CD4+ T cells from patients with HBV-ACLF, and are positively correlated with disease severity, prognosis, and infection complications. BTLA levels were upregulated by the IL-6 and TNF signaling pathways. Antibody crosslinking of BTLA activated the PI3K-Akt pathway to inhibit the activation, proliferation, and cytokine production of CD4+ T cells while promoting their apoptosis. In contrast, BTLA knockdown promoted their activation and proliferation. BTLA-/- ACLF mice exhibited increased cytokine secretion, and reduced mortality and bacterial burden. The administration of a neutralizing anti-BTLA antibody reduced Klebsiella pneumoniae load and mortality in mice with ACLF. These data may help elucidate HBV-ACLF pathogenesis and aid in identifying novel drug targets.

Corrigendum: Difference of gut microbiota between patients with negative and positive HBeAg in chronic hepatitis B and the effect of tenofovir alafenamide on intestinal flora.

[This corrects the article DOI: 10.3389/fmicb.2023.1232180.].

Difference of gut microbiota between patients with negative and positive HBeAg in chronic hepatitis B and the effect of tenofovir alafenamide on intestinal flora.

Background: Severe liver diseases, such as liver fibrosis, cirrhosis, and liver cancer, are mainly caused by hepatitis B virus (HBV). This study investigated the differences between gut microbiota in HBeAg-positive and negative groups of patients with chronic hepatitis B (CHB) and investigated the effect of tenofovir alafenamide (TAF) on gut microbiota. Methods: This prospective study included patients with CHB not taking nucleoside antivirals (No-NAs group, n = 95) and those taking TAF (TAF group, n = 60). We divided CHB patients into two groups according to the HBeAg status of the subjects on the day of data collection. Phase 1 are HBeAg-negative patients and phase 2 are HBeAg-positive patients. We investigated the improvement of clinical symptoms by TAF, as well as differences in gut microbiota between different groups by 16S rRNA high-throughput sequencing. Results: Gut microbiota demonstrated significant differences between patients with HBeAg-positive and -negative CHB. Both the No-NAs and TAF Phase 2 subgroups demonstrated significantly increased microbiota richness and diversity, showing greater heterogeneity. Additionally, the Phase 2 subgroup exhibited a low abundance of pathways associated with glucose metabolism and amino acid metabolism. The TAF group demonstrated a significantly decreased HBV load, alanine aminotransferase, and aspartate aminotransferase and a significant increase in prealbumin compared with the No-NAs group. No significant difference was found in uric acid, creatinine, blood calcium, inorganic phosphorus, eGFR, and ß2-microglobulin concentrations between the two groups. Additionally, the urea level in the TAF group was significantly lower than that in the No-NAs group, but with no significant effect on other indicators such as eGFR and ß2-microglobulin. Conclusion: This study revealed significant differences in gut microbiota composition and function between patients with HBeAg-positive and -negative CHB.

Z-Scheme Heterojunction of SnS2/Bi2WO6 for Photoreduction of CO2 to 100% Alcohol Products by Promoting the Separation of Photogenerated Charges.

Using sunlight to convert CO2 into solar fuel is an ideal solution to both global warming and the energy crisis. The construction of direct Z-scheme heterojunctions is an effective method to overcome the shortcomings of single-component or conventional heterogeneous photocatalysts for photocatalytic CO2 (carbon dioxide) reduction. In this work, a composite photocatalyst of narrow-gap SnS2 and stable oxide Bi2WO6 were prepared by a simple hydrothermal method. The combination of Bi2WO6 and SnS2 narrows the bandgap, thereby broadening the absorption edge and increasing the absorption intensity of visible light. Photoluminescence, transient photocurrent, and electrochemical impedance showed that the coupling of SnS2 and Bi2WO6 enhanced the efficiency of photogenerated charge separation. The experimental results show that the electron transfer in the Z-scheme heterojunction of SnS2/Bi2WO6 enables the CO2 reduction reactions to take place. The photocatalytic reduction of CO2 is carried out in pure water phase without electron donor, and the products are only methanol and ethanol. By constructing a Z-scheme heterojunction, the photocatalytic activity of the SnS2/Bi2WO6 composite was improved to 3.3 times that of pure SnS2.

High-throughput lateral and basal interface in CeO2@Ti3C2TX: Reverse and synergistic migration of carrier for enhanced photocatalytic CO2 reduction.

Rational construction of heterogeneous interfaces that maximize carrier flux and allow carrier separation for achieving efficient photocatalytic CO2 reduction still remain a challenge. In this work, high-throughput and intimate interfaces that allow efficient carrier separation and flux are designed by depositing high-density CeO2 nanoparticles on large-area Ti3C2TX (T = terminal group) nanosheets. Oxygen-containing functional groups of Ti3C2TX nanosheets facilitate the anchoring of CeO2 nanoparticles on the nanosheets via the formation of interfacial Ce-O-Ti bonds, which serve as effective channels for reverse and synergistic migration of electrons and holes to achieve spatial separation. The light absorption of the CeO2@Ti3C2TX composites is extended to the infrared (IR) region due to narrow bandgaps of Ti3C2TX. High-density lateral and basal interfaces enhance carrier migration, which ultimately aids the CeO2@Ti3C2TX composites to exhibit excellent activity for reducing CO2 to alcohols (i.e., methanol and ethanol) under both visible (vis) and IR irradiations. The total amount of produced alcohol under visible irradiation is 109.9 µmol•gcatal-1 (methanol and ethanol: 76.2 and 33.7 µmol•gcatal-1, respectively), which is 4.3 times higher than that obtained using CeO2 (methanol and ethanol: 19.8 and 6 µmol•gcatal-1, respectively). The yields of methanol and ethanol using the optimized CeO2@Ti3C2TX were 102.24 and 59.21 µmol•gcatal-1, respectively, after 4 h under the vis-IR irradiation.

Potential Molecular Biomarkers of Vestibular Schwannoma Growth: Progress and Prospects.

Vestibular schwannomas (VSs, also known as acoustic neuromas) are relatively rare benign brain tumors stem from the Schwann cells of the eighth cranial nerve. Tumor growth is the paramount factor for neurosurgeons to decide whether to choose aggressive treatment approach or careful follow-up with regular magnetic resonance imaging (MRI), as surgery and radiation can introduce significant trauma and affect neurological function, while tumor enlargement during long-term follow-up will compress the adjacent nerves and tissues, causing progressive hearing loss, tinnitus and vertigo. Recently, with the deepening research of VS biology, some proteins that regulate merlin conformation changes, inflammatory cytokines, miRNAs, tissue proteins and cerebrospinal fluid (CSF) components have been proposed to be closely related to tumor volume increase. In this review, we discuss advances in the study of biomarkers that associated with VS growth, providing a reference for exploring the growth course of VS and determining the optimal treatment strategy for each patient.

Comprehensive pharmacogenomics characterization of temozolomide response in gliomas.

Recent developments in pharmacogenomics have created opportunities for predicting temozolomide response in gliomas. Temozolomide is the main first-line alkylating chemotherapeutic drug together with radiotherapy as standard treatments of high-risk gliomas after surgery. However, there are great individual differences in temozolomide response. Besides the heterogeneity of gliomas, pharmacogenomics relevant genetic polymorphisms can not only affect pharmacokinetics of temozolomide but also change anti-tumor effects of temozolomide. This review will summarize pharmacogenomic studies of temozolomide in gliomas which can lay the foundation to personalized chemotherapy.

A Review of Drug Therapy in Vestibular Schwannoma.

Vestibular schwannomas (VSs, also known as acoustic neuromas) are benign intracranial tumors commonly managed with observation, surgery, and radiotherapy. There is currently no approved pharmacotherapy for VS patients, which is why we conducted a detailed search of relevant literature from PubMed and Web of Science to explore recent advances and experiences in drug therapy. VSs feature a long course of disease that requires treatment to have minimal long-term side effects. Conventional chemotherapeutic agents are characterized by neurotoxicity or ototoxicity, poor effect on slow-growing tumors, and may induce new mutations in patients who have lost tumor suppressor function, and therefore are unsuitable for treating VSs. Along with the well-investigated molecular pathophysiology of VS and the increasingly accessible technology such as drug repositioning platform, many molecular targeted inhibitors have been identified and shown certain therapeutic effects in preclinical experiments or clinical trials.

A promising non-invasive index for predicting liver inflammation in chronic hepatitis B patients with alanine aminotransferase ≤2 upper limit of normal.

Inexpensive and simple non-invasive indexes for predicting liver inflammation are urgently required, but have been poorly studied in chronic hepatitis B (CHB) patients with alanine transaminase (ALT) ≤2 times the upper limit of normal (ULN). A total of 356 CHB patients with ALT ≤2 ULN who presented at Huashan Hospital (n=181) and the First Hospital of Quanzhou (n=175) were enrolled and randomly divided into an experimental assessment cohort (n=238) and validation cohort (n=118) at a ratio of 2:1. Histological analysis of liver tissue was performed to determine the pathological stage according to the Scheuer scoring system. For the experimental assessment cohort, univariate and multivariate analysis identified aspartate aminotransferase (AST) and albumin (ALB) as independent predictors of liver necroinflammation [liver necroinflammation grade (G)≥2] in patients with ALT ≤2 ULN. Therefore, a novel index, the AST-to-ALB ratio (ATAR), was proposed, which had a better diagnostic performance [area under receiver operating characteristic curve (AUC)=0.721] than that of ALB (AUC=0.632; P=0.039 vs. ATAR) and AST (AUC=0.682; P=0.082 vs. ATAR). In the validation cohort, the AUC of ATAR (0.728) to identify patients with a G≥2 was slightly greater than that of AST (0.660; P=0.149 vs. ATAR) and ALB (0.672; P=0.282 vs. ATAR). Furthermore, a similar diagnostic superiority was also demonstrated in patients with ALT ≤1 ULN. Thus, ATAR may be a promising non-invasive surrogate marker for liver necroinflammation CHB patients with ALT ≤2 ULN and thereby determine whether anti-viral treatment should be initiated.

Induced cortical neurogenesis after focal cerebral ischemia--Three active components from Huang-Lian-Jie-Du Decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Lian-Jie-Du-Decoction (HLJDD) is a Traditional Chinese Medicine (TCM) clinical prescription noted for its neuroprotective effects. The total alkaloids, flavonoids, and iridoids are the main active components of HLJDD. In the present study we explored the possible effects of the total alkaloids, flavonoids, and iridoids from HLJDD on behavioral recovery and cortical neurogenesis after stroke. METHODS: The stroke model was induced by permanent middle cerebral artery occlusion (pMACO). The total alkaloids (44 mg/kg), flavonoids (50 mg/kg), and iridoids (80 mg/kg) from HLJDD were orally administered for 2h after stroke and daily thereafter. Neurological function was assessed and then rats were sacrificed 7 days after pMACO. Following repeated intraperitoneal injections of the cell proliferation - specific marker 5-bromodeoxyuridine (BrdU) after stroke induction, precursor cell proliferation and differentiation was monitored by immunofluorescent staining. The levels of relevant proteins were determined by western blotting and the mRNA expressions were assessed by quantitative real time-polymerase chain reaction (qRT-PCR). RESULTS: Total alkaloids, flavonoids and iridoids from HLJDD showed improved functional outcome after brain ischemia. The total alkaloids and iridoids increased number of BrdU-positive cells and enhanced neuronal differentiation in the cortex. Alkaloids-enhanced neurogenesis might be associated with increased VEGF, Ang-1, and Ang-2 protein expression. And the neuroproliferative effect of alkaloids was partially correlated with increased phosphorylation of AKT, and GSK-3ß. Flavonoids treatment was found to promote differentiation of cortical precursor cells into neuronal but not glial cells, which may be at least attributable to the regulation of AKT, GSK-3ß mRNA and Ang-1 protein levels. CONCLUSIONS: Total alkaloids, iridoids and flavonoids from HLJDD promoted functional recovery likely via enhancing cortical neurogenesis and thus have potential as a treatment for ischemic brain injury.

[Huanglian jiedu decoction active fraction protects ipsilateral thalamus injury in MCAO rats through regulating astrocytes].

OBJECTIVE: To observe the protective effects of the Huanglian Jiedu decoction aqueous extract and its active fraction, which consists of total alkaloids, total flavonoids and total iridoid, on the thalamus of cerebral ischemia in rats. METHOD: The rat model of middle cerebral artery occlusion (MCAO) was chosen. Male SD rats were randomly divided into sham-operation group, model group, aqueous extract group (800 mg x kg(-1)), total alkaloids group(44 mg x kg(-1)), total flavonoids group (50 mg x kg(-1)) and the total iridoid group (80 mg x kg(-1)). The rats were administered the appropriate drugs intragastrically once a day, for 7 days after surgery. An equivalent volume of saline was given in the sham surgery and model groups. The HE staining was adopted to observe the pathological changes. Determination of Glu and gamma-GABA in thalamus were detected by HPLC with fluorescence detection. The expression of GAD65 was examined with immunohistochemistry and double staining with uorescent-conjugated antibodies against GFAP and Cx43 was chosen in this study. RESULT: The neurons degenerated in MCAO rats after cerebral ischemia 7 d. The content of Glu, gamma-GABA decreased (P < 0.05), the expression of GAD65 reduced (P < 0.05) and the expression of GFAP and Cx43 increased (P < 0.01) in thalamus of rats compared with sham-operation group. Huanglian Jiedu decoction aqueous extract, total alkaloids, total flavonoids and total iridoid reduced the degeneration of neurons. Total flavonoids could promote the expression of GAD65 (P < 0.05) and decrease the expression of GFAP and Cx43 (P < 0.01) in thalamus compared with model group while it could also increased the content of Glu,gamma-GA BA to normal levels. Compared with model group, Huanglian Jiedu decoction aqueous extract, total alkaloids and total iridoid could raise the expression of Cx43, and Huanglian Jiedu decoction aqueous extract could also increase the expression of GAD65 (P < 0.05). The expression of GFAP in Huanglian Jiedu decoction aqueous extract group, total alkaloids group and total iridoid group were not different compared with model group while the content of gamma-GABA decreased (P < 0.05) compared with sham-operation group. CONCLUSION: The degeneration of nerve cells, the reduction of neurotransmitter amino acids content, the aberrant activation of astrocytes and the abnormal expression of GFAP and Cx43 will appear in thalamus of MCAO rats after ischemia. Huanglian Jiedu decoction total flavonoids could relieve the injury of nerve cell through inhibiting the abnormal activation of astrocytes and regulating the expression of GFAP and GAD65.