Lattice Manipulation with Di-Tertiary Ammonium Spacer in Bismuth Bromide Perovskite Directs Efficient Charge Transport and Suppressed Ion Migration for Photodetector Applications.

Bismuth halide hybrid perovskites have emerged as promising alternatives to their lead halide homologs because of high chemical stability, low toxicity, and structural diversity. However, their advancements in optoelectronic field are plagued with poor charge transport, due to considerable microstrain triggered by bulky spacer. Herein, the di-tertiary ammonium spacer (N,N,N',N'-tetramethyl-1,4-butanediammonium, TMBD) is explored to direct stable 1D bismuth bromide lattice structure with relaxed microstrain. Compared to the primary pentamethylenediamine (PD)2+, the (TMBD)2+ adopting alternating alignment enables a unique H-bonds mode to distort the configuration of inorganic layers to form corner-sharing [BiBr5] near-regular chains with narrower bandgap, lower exciton binding energy, and reduced carrier-lattice interactions, thereby facilitating charge-carrier transport. Moreover, the (TMBD)2+ spacers largely suppress ion migration in perovskite lattice, as substantiated by the experimental and theoretical investigations. Consequently, (TMBD)BiBr5 single crystal photodetector delivers a 185-fold increase in current on/off ratio with respect to (PD)BiBr5 under white light irradiation, considerable responsivity (≈82.97 mA W-1), detectivity (≈8.06 ×1011 Jones) under weak light (0.02 mW cm-2) irradiation, in the top rank of the reported hybrid bismuth halide perovskites. This finding offers novel design criterion for high-performance lead-free perovskites.

Effects of Drought Stress on Photosynthesis and Chlorophyll Fluorescence in Blue Honeysuckle.

Blue honeysuckle (Lonicera caerulea L.) is a deciduous shrub with perennial rootstock found in China. The objectives of this study were to explore the drought tolerance of blue honeysuckle, determine the effect of drought stress on two photosystems, and examine the mechanism of acquired drought tolerance. In this study, blue honeysuckle under four levels of simulated field capacity (100%, 85%, 75%, and 65% RH) was grown in split-root pots for drought stress treatment, for measuring the changes in chlorophyll content, photosynthetic characteristics, and leaf chlorophyll fluorescence parameters. The chlorophyll content of each increased under mild stress and decreased under moderate and severe stress. The net photosynthetic rate, transpiration rate, intercellular carbon dioxide concentration, and stomatal conductance of blue honeysuckle decreased with the increase in water stress. However, the water utilization rate and stomatal limit system increased under mild and moderate stress and decreased under severe stress. The maximum fluorescence (Fm), maximum photochemical efficiency, and quantum efficiency of photosystem II decreased with the decrease in soil water content, and the initial fluorescence increased significantly (p < 0.01). With the decrease in soil water content, the energy allocation ratio parameters decreased under severe drought stress. The main activity of the unit reaction center parameters first increased and then decreased. ABS/CSm, TRo/CSm, ETo/CSm, and REo/CSm gradually declined. After a comprehensive analysis, the highest scores were obtained under adequate irrigation (CK). Overall, we concluded that the water irrigation system of blue honeysuckle should be considered adequate.

Prognostic significance of dynamic changes in liver stiffness measurement in patients with chronic hepatitis B and compensated advanced chronic liver disease.

BACKGROUND AND AIM: Liver stiffness measurements (LSMs) are promising for monitoring disease progression or regression. We assessed the prognostic significance of dynamic changes in LSM over time on liver-related events (LREs) and death in patients with chronic hepatitis B (CHB) and compensated advanced chronic liver disease (cACLD). METHODS: This retrospective study included 1272 patients with CHB and cACLD who underwent at least two measurements, including LSM and fibrosis score based on four factors (FIB-4). ΔLSM was defined as [(follow-up LSM - baseline LSM)/baseline LSM × 100]. We recorded LREs and all-cause mortality during a median follow-up time of 46 months. Hazard ratios (HRs) and confidence intervals (CIs) for outcomes were calculated using Cox regression. RESULTS: Baseline FIB-4, baseline LSM, ΔFIB-4, ΔLSM, and ΔLSM/year were independently and simultaneously associated with LREs (adjusted HR, 1.04, 95% CI, 1.00-1.07; 1.02, 95% CI, 1.01-1.03; 1.06, 95% CI, 1.03-1.09; 1.96, 95% CI, 1.63-2.35, 1.02, 95% CI, 1.01-1.04, respectively). The baseline LSM combined with the ΔLSM achieved the highest Harrell's C (0.751), integrated AUC (0.776), and time-dependent AUC (0.737) for LREs. Using baseline LSM and ΔLSM, we proposed a risk stratification method to improve clinical applications. The risk proposed stratification based on LSM performed well in terms of prognosis: low risk (n = 390; reference), intermediate risk (n = 446; HR = 3.38), high risk (n = 272; HR = 5.64), and extremely high risk (n = 164; HR = 11.11). CONCLUSIONS: Baseline and repeated noninvasive tests measurement allow risk stratification of patients with CHB and cACLD. Combining baseline and dynamic changes in the LSM improves prognostic prediction.

Novel solution-gated transistor sensor-based SnO2 epitaxial thin films grown by pulsed laser deposition for nitrite detection.

A solution-gate controlled thin-film transistor with SnO2 epitaxial thin films (SnO2-SGTFT) is successfully utilized for highly sensitive detection of nitrite. The SnO2 films are deposited as channel materials on a c-plane sapphire (c-Al2O3) substrate through pulsed laser deposition (PLD), with superior crystal quality and out-of-plane atomic ordering. PtAu NPs/rGO nanocomposites are electrodeposited on a gold electrode to function as a transistor gate to further enhance the nitrite catalytic performance of the device. The change in effective gate voltage due to the electrooxidation of nitrite on the gate electrode is the primary sensing mechanism of the device. Based on the inherent amplification effect of transistors, the superior electrical properties of SnO2, and the high electrocatalytic activity of PtAu NPs/rGO, the SnO2-SGTFT sensor has a low detection limit of 0.1 nM and a wide linear detection range of 0.1 nM ~ 50 mM at VGS = 1.0 V. Furthermore, the sensor has excellent characteristics such as rapid response time, selectivity, and stability. The practicability of the device has been confirmed by the quantitative detection of nitrite in natural lake water. SnO2 epitaxial films grown by PLD provide a simple and efficient way to fabricate nitrite SnO2-SGTFT sensors in environmental monitoring and food safety, among others. It also provides a reference for the construction of other high-performance thin-film transistor sensors.

Biocompatible Perovskite Nanocrystals with Enhanced Stability for White Light-Emitting Diodes.

Recently emerged lead halide perovskite CsPbX3 (X = Cl, Br, and I) nanocrystals (PNCs) have attracted tremendous attention due to their excellent optical properties. However, the poor water stability, unsatisfactory luminescence efficiency, disappointing lead leakage, and toxicity have restricted their practical applications in photoelectronics and biomedical fields. Herein, a controllable encapsulated strategy is investigated to realize CsPbX3 PNCs/PVP @PMMA composites with superior luminescence properties and excellent biocompatibility. Additionally, the synthesized CsPbBr3 and CsPbBr0.6I2.4 PNCs/PVP@PMMA structures exhibit green and red emissions with a maximal photoluminescence quantum yield (PLQY) of about 70.24% and 98.26%, respectively. These CsPbX3 PNCs/PVP@PMMA structures show high emission efficiency, excellent stability after water storage for 18 months, and low cytotoxicity at the PNC concentration at 500 µg mL-1. Moreover, white light-emitting diode (WLED) devices based on mixtures of CsPbBr3 and CsPbBr0.6I2.4 PNCs/PVP@PMMA perovskite structures are investigated, which exhibit excellent warm-white light emissions at room temperature. A flexible manipulation method is used to fabricate the white light emitters based on these perovskite composites, providing a fantastic platform for fabricating solid-state white light sources and full-color displays.

The steatosis-associated fibrosis estimator (SAFE) outperformed the FIB-4 score in screening the population for liver disease.

INTRODUCTION AND OBJECTIVES: Assessing fibrosis risk noninvasively is essential. The steatosis-associated fibrosis estimator (SAFE) score shows promise but needs validation. PATIENTS AND METHODS: This was a three-part study. In part 1, we compared the SAFE score with the Fibrosis-4 (FIB-4) and NAFLD fibrosis score (NFS) in the National Health and Nutrition Examination Survey (NHANES) cohort (2017-2020), using transient elastography (TE) as screening reference. In part 2, we examined patients who underwent liver biopsies at an Asian center between 2018 and 2020 to assess these models in various liver diseases. In part 3, the SAFE score was applied to adults in the NHANES cohort (1999-2016) to assess the correlation with mortality. RESULTS: In part 1, we studied 6,677 patients, comprising 595 screening positive (TE ≥8 kPa). SAFE (cutoff 100) displayed a lower proportion of false positives (10.4 %) than FIB-4 (cutoff 1.3) and NFS (cutoff -1.455) (22.1 % and 43.6 %) while retaining a low proportion of false negatives (5.5 %). In part 2, SAFE outperformed FIB-4 (P = 0.04) and NFS (P = 0.04) in staging significant fibrosis (≥S2) in NAFLD and had similar accuracies in other etiologies. In part 3, the FIB-4, NFS, and SAFE score were associated with all-cause mortality in the general population, with c-statistics of 0.738, 0.736, and 0.759, respectively. CONCLUSIONS: The SAFE score reduced futile referrals more effectively than FIB-4 without raising the missed TE ≥ 8 kPa rate. It correlated with all-cause mortality in the general population and excelled in staging significant fibrosis in NAFLD.

Proton pump inhibitor use is associated with increased liver steatosis.

Despite proton pump inhibitors (PPIs) being generally safe, there are questions about their potential long-term complications. The present study aimed to investigate the association between PPI therapy and the incidence of hepatic steatosis and liver fibrosis in the outpatient population of the United States. The present study included 7,395 individuals aged ≥20 years who underwent hepatic vibration-controlled transient elastography (VCTE) examination. The data were obtained from the January 2017 to March 2020 pre-pandemic National Health and Nutrition Examination Survey. Among the 7,395 adults who were included (mean age, 50.59 years; 3,656 male), 9.8% were prescribed PPIs. Following multivariable adjustment, the use of PPIs was significantly associated with hepatic steatosis [odds ratio (OR), 1.25; 95% confidence interval (CI), 1.02-1.53]. Prolonged use of PPIs was found to increase the risk of developing hepatic steatosis over time (P=0.006). Sensitivity analyses using different definitions of hepatic steatosis, such as a controlled attenuation parameter ≥285 dB/m (OR, 1.19; CI, 1.01-1.40), non-alcoholic fatty liver disease (OR, 1.50; 95% CI, 1.16-1.93) and metabolic dysfunction-associated steatotic liver disease (OR, 1.26; 95% CI, 1.05-1.52), consistently demonstrated an association between PPI prescription and hepatic steatosis. The administration of PPI therapy was linked with hepatic steatosis in US adults, although no significant association was observed with liver stiffness, as determined by VCTE.

Optimization of Dendritic Polypeptide Delivery System for Antisense Antibacterial Agents Targeting ftsZ.

There is an urgent requirement for a novel treatment strategy for drug-resistant Staphylococcus aureus (S. aureus) infection. Antisense antimicrobials are promising antimicrobials, and efficient drug delivery systems are necessary for the further development of antisense antimicrobials. To develop new antisense drugs and further improve delivery efficiency and safety, we designed and screened new antisense sequences and optimized dendritic polypeptide nanoparticles (DP-AD) discovered in previous studies. The N/P ratio is optimized from 8:1 to 6:1, and the positive charge number of the optimized DP-AD is studied comprehensively. The results show that the N/P ratio and positive charge number have no significant effect on the particle size distribution and transport efficiency of DP-AD. Reducing the N/P ratio can significantly reduce the cytotoxicity of DP-AD, but it does not affect its delivery efficiency and antibacterial activity. However, in drug-resistant strains, the antibacterial activity of DP-AD76:1 with 10 positive charges is higher than that of DP-AD86:1 with 8 positive charges. Our research discovered a novel ASOs targeting ftsZ and concluded that DP-AD76:1 with 10 positive charges was the optimal choice at the current stage, which provided a promising strategy for the treatment of drug-resistant S. aureus.

Prediction model of early recurrence of multimodal hepatocellular carcinoma with tensor fusion.

Objective.In oncology, clinical decision-making relies on a multitude of data modalities, including histopathological, radiological, and clinical factors. Despite the emergence of computer-aided multimodal decision-making systems for predicting hepatocellular carcinoma (HCC) recurrence post-hepatectomy, existing models often employ simplistic feature-level concatenation, leading to redundancy and suboptimal performance. Moreover, these models frequently lack effective integration with clinically relevant data and encounter challenges in integrating diverse scales and dimensions, as well as incorporating the liver background, which holds clinical significance but has been previously overlooked.Approach.To address these limitations, we propose two approaches. Firstly, we introduce the tensor fusion method to our model, which offers distinct advantages in handling multi-scale and multi-dimensional data fusion, potentially enhancing overall performance. Secondly, we pioneer the consideration of the liver background's impact, integrating it into the feature extraction process using a deep learning segmentation-based algorithm. This innovative inclusion aligns the model more closely with real-world clinical scenarios, as the liver background may contain crucial information related to postoperative recurrence.Main results.We collected radiomics (MRI) and histopathological images from 176 cases diagnosed by experienced clinicians across two independent centers. Our proposed network underwent training and 5-fold cross-validation on this dataset before validation on an external test dataset comprising 40 cases. Ultimately, our model demonstrated outstanding performance in predicting early recurrence of HCC postoperatively, achieving an AUC of 0.883.Significance.These findings signify significant progress in addressing challenges related to multimodal data fusion and hold promise for more accurate clinical outcome predictions. In this study, we exploited global 3D liver background into modelling which is crucial to to the prognosis assessment and analyzed the whole liver background in addition to the tumor region. Both MRI images and histopathological images of HCC were fused at high-dimensional feature space using tensor techniques to solve cross-scale data integration issue.

Bulk Photovoltaic Effect in Polar 3D Perovskitoid Enables Self-Powered Polarization-Sensitive Photodetection.

The family of polar hybrid perovskites, in which bulk photovoltaic effects (BPVEs) drive steady photocurrent without bias voltage, have shown promising potentials in self-powered polarization-sensitive photodetection. However, reports of BPVEs in 3D perovskites remain scare, being mainly hindered by the limited dipole moment or lack of symmetry breaking. Herein, a polar 3D perovskitoid, (BDA)Pb2Br6 (BDA = NH3C4H8NH3), where the spontaneous polarization (Ps)-induced BPVE drives self-powered photodetection of polarized-light is reported. Emphatically, the edge-sharing Pb2Br10 dimer building unit allows the optical anisotropy and polarity in 3D (BDA)Pb2Br6, which triggers distinct optical absorption dichroism ratio of ≈2.80 and BPVE dictated photocurrent of 3.5 µA cm-2. Strikingly, these merits contribute to a polarization-sensitive photodetection with a high polarization ratio (≈4) under self-powered mode, beyond those of 2D hybrid perovskites and inorganic materials. This study highlights the potential of polar 3D perovskitoids toward intelligent optoelectronic applications.

The microbial biosynthesis of noncanonical terpenoids.

Terpenoids are a class of structurally complex, naturally occurring compounds found predominantly in plant, animal, and microorganism secondary metabolites. Classical terpenoids typically have carbon atoms in multiples of five and follow well-defined carbon skeletons, whereas noncanonical terpenoids deviate from these patterns. These noncanonical terpenoids often result from the methyltransferase-catalyzed methylation modification of substrate units, leading to irregular carbon skeletons. In this comprehensive review, various activities and applications of these noncanonical terpenes have been summarized. Importantly, the review delves into the biosynthetic pathways of noncanonical terpenes, including those with C6, C7, C11, C12, and C16 carbon skeletons, in bacteria and fungi host. It also covers noncanonical triterpenes synthesized from non-squalene substrates and nortriterpenes in Ganoderma lucidum, providing detailed examples to elucidate the intricate biosynthetic processes involved. Finally, the review outlines the potential future applications of noncanonical terpenoids. In conclusion, the insights gathered from this review provide a reference for understanding the biosynthesis of these noncanonical terpenes and pave the way for the discovery of additional unique and novel noncanonical terpenes. KEY POINTS: •The activities and applications of noncanonical terpenoids are introduced. •The noncanonical terpenoids with irregular carbon skeletons are presented. •The microbial biosynthesis of noncanonical terpenoids is summarized.

Upregulation of TRPC1 in microglia promotes neutrophil infiltration after ischemic stroke.

Neutrophil infiltration has been linked to worse clinical outcomes after ischemic stroke. Microglia, a key type of immune-competent cell, engage in cross-talk with the infiltrating immune cells in the inflamed brain area, yet the molecular mechanisms involved remain largely unexplored. In this study, we investigated the mechanisms of how canonical transient receptor potential 1 (TRPC1) modulated neutrophil infiltration in male mouse cerebral ischemia and reperfusion injury (CIRI) models. Our findings revealed a notable upregulation of TRPC1 in microglia within both middle cerebral artery occlusion reperfusion (MCAO/R) and in vitro oxygen-glucose deprivation/regeneration (OGD/R) model. Conditional Trpc1 knockdown in microglia markedly reduced infarct volumes and alleviated neurological deficits. Microglia conditional Trpc1 knockdown mice displayed less neutrophil infiltration in peri-infarct area. Trpc1 knockdown microglia exhibited a reduced primed proinflammatory phenotype with less secretion of CC-Chemokines ligand (CCL) 5 and CCL2 after MCAO/R. Blocking CCL5/2 significantly mitigated neutrophil infiltration in microglia/neutrophil transwell co-culture system upon OGD/R condition. Trpc1 knockdown markedly reduced store-operated calcium entry and nuclear factor of activated T-cells c1 (NFATc1) level in OGD/R treated microglia. Overexpression of Nfatc1 reversed the CCL5/2 reducing effect of Trpc1 knockdown, which is mediated by small interfering RNA in BV2 cells upon OGD/R. Our data indicate that upregulation of TRPC1 in microglia stimulates the production of CCL5/2 through the Ca2+/NFATc1 pathway. Upregulated CCL5/2 leads to an increase in neutrophil infiltration into the brain, thereby aggravating reperfusion injury. Our results demonstrate the importance of TRPC1 in microglia-mediated neuroinflammation and suggest a potential means for reducing CIRI induced neurological injury.

Mean ADC values and arterial phase hyperintensity discriminate small (≤ 3 cm) well-differentiated hepatocellular carcinoma from dysplastic nodule.

BACKGROUND/AIM: This research endeavor sought to distinguish small (≤ 3 cm) well-differentiated hepatocellular carcinoma (WD-HCC) from dysplastic nodules (DN) by employing traditional imaging features and mean apparent diffusion coefficient (mADC) values derived from diffusion-weighted imaging (DWI). MATERIALS AND METHODS: In this retrospective analysis, we assessed a cohort of ninety patients with confirmed dysplastic nodules (DNs) (n = 71) or well-differentiated hepatocellular carcinoma (WD-HCC) (n = 41) who had undergone dynamic contrast-enhanced magnetic resonance imaging between March 2018 and June 2021. Multivariable logistic regression analyses were executed to pinpoint characteristics that can effectively differentiate histologic grades. A region-of-interest (ROI) encompassing all lesion voxels was delineated on each slice containing the mass in the ADC map. Subsequently, the whole-lesion mean ADC (mADC) were computed from these delineations. A receiver operating characteristic (ROC) curve was generated to assess the discriminatory efficacy of the mADC values in distinguishing between WD-HCC and DN. RESULTS: Among the histopathological types from benign to malignant, mADC showed a significant decrease (P < 0.001). The mADCs were effective in distinguishing WD-HCC from DN [AUC, 0.903 (95% CI 0.849-0.958)]. The best cutoffs for the Youden index were 0.0012 mm2/s for mADC, with moderate sensitivity (70.7%) and high specificity (94.4%). MRI features including hyperintensity at arterial phase (odds ratio, 21.2; P = 0.009), mADC < 0.0012 mm2/s (odds ratio, 52.2; P < 0.001) were independent predictors for WD-HCC at multivariable analysis. The AUC value of hyperintensity at arterial phase was 0.857 (95% CI 0.786-0.928). The composite diagnostic criterion of arterial hyperintensity + mADC < 0.0012 mm2/s showed good performance [AUC, 0.926 (95% CI 0.878-0.975)], displaying increased sensitivity compared to individual assessments involving arterial hyperintensity (P = 0.013), mADC < 0.0012 mm2/s (P = 0.004), or LR-5 (P < 0.001), with similar specificity compared to LR-5 (P = 0.193). CONCLUSION: DN and WD-HCC displayed contrasting diffusion characteristics, attainable to distinguish with satisfactory accuracy. The utilization of arterial phase hyperintensity and mADC < 0.0012 on MRI facilitated the differentiation of WD-HCC from DN.

Halide Ordering Enables Superior Charge Transport in 3D (NMPDA)Pb2 I4 Br2 Perovskitoid Single Crystal.

Halide composition engineering has been demonstrated as an effective strategy for optical and electronic properties modulation in 3D perovskites. While the impact of halide mixing on the structural and charge transport properties of 3D perovskitoids remains largely unexplored. Herein, it is demonstrated that bromine (Br) mixing in 3D (NMPDA)Pb2 I6 (NMPDA = N-methyl-1,3-propane diammonium) perovskitoid yields stabilized (NMPDA)Pb2 I4 Br2 with specific ordered halide sites, where Br ions locate at the edge-sharing sites. The halide ordered structure enables stronger H-bonds, shorter interlayer distance, and lower octahedra distortion in (NMPDA)Pb2 I4 Br2 with respect to the pristine (NMPDA)Pb2 I6 . These attributes further result in high ion migration activation energy, low defect states density, and enhanced carrier mobility-lifetime product (µτ), as underpinned by the electrical properties investigation and DFT calculations. Remarkably, the parallel configured photodetector based on (NMPDA)Pb2 I4 Br2 single crystal delivers a high on/off current ratio of 3.92 × 103 , a satisfying photoresponsivity and detectivity of 0.28 A W-1 and 3.05 × 1012 Jones under 10.94 µW cm-2 irradiation, superior to that of (NMPDA)Pb2 I6 and the reported 3D perovskitoids. This work sheds novel insight on exploring 3D mixed halide perovskitoids toward advanced and stable optoelectronic devices.

Broadband red emission from one-dimensional hexamethonium lead bromide perovskitoid.

Broadband emissions from low-dimensional hybrid perovskites have aroused intense interest. However, the achievement of broadband red emission in lead halide perovskites remains challenging. Herein, we report a one-dimensional (1D) hybrid lead bromide perovskitoid, (HM)Pb2Br6 (HM = hexamethonium), featuring a corrugated "3 × 3" [Pb2Br6]2- chain. The unique structure results in intriguingly red emission peaking at 692 nm, with a PLQY of around 6.24%. Our spectroscopic and computational studies reveal that the red emission derives from self-localized Pb23+, Pb3+ and Br2- species confined within the inorganic lead bromide lattice that function as radiative centres. This finding will benefit the design of perovskite systems for efficient red emission.

Lowering the threshold of alanine aminotransferase for enhanced identification of significant hepatic injury in chronic hepatitis B patients.

BACKGROUND: The clinical and histological features of chronic hepatitis B (CHB) patients who fall into the "grey zone (GZ)" and do not fit into conventional natural phases are unclear. AIM: To explore the impact of varying the threshold of alanine aminotransferase (ALT) levels in identifying significant liver injury among GZ patients. METHODS: This retrospective analysis involved a cohort of 1617 adult patients diagnosed with CHB who underwent liver biopsy. The clinical phases of CHB patients were determined based on the European Association for the Study of the Liver 2017 Clinical Practice Guidelines. GZ CHB patients were classified into four groups: GZ-A (HBeAg positive, normal ALT levels, and HBV DNA ≤ 107 IU/mL), GZ-B (HBeAg positive, elevated ALT levels, and HBV DNA < 104 or > 107 IU/mL), GZ-C (HBeAg negative, normal ALT levels, and HBV DNA ≥ 2000 IU/mL), and GZ-D (HBeAg negative, elevated ALT levels, and HBV DNA ≤ 2000 IU/mL). Significant hepatic injury (SHI) was defined as the presence of notable liver inflammation (≥ G2) and/or significant fibrosis (≥ S2). RESULTS: The results showed that 50.22% of patients were classified as GZ, and 63.7% of GZ patients developed SHI. The study also found that lowering the ALT treatment thresholds to the American Association for the Study of Liver Diseases 2018 treatment criteria (35 U/L for men and 25 U/L for women) can more accurately identify patients with significant liver damage in the GZ phases. In total, the proportion of patients with ALT ≤ 40 U/L who required antiviral therapy was 64.86% [(221 + 294)/794]. When we lowered the ALT treatment threshold to the new criteria (30 U/L for men and 19 U/L for women), the same outcome was revealed, and the proportion of patients with ALT ≤ 40 U/L who required antiviral therapy was 75.44% [(401 + 198)/794]. Additionally, the proportion of SHI was 49.1% in patients under 30 years old and increased to 55.3% in patients over 30 years old (P = 0.136). CONCLUSION: These findings suggest the importance of redefining the natural phases of CHB and using new ALT treatment thresholds for better diagnosis and management of CHB patients in the GZ phases.

Enhancing Spns2/S1P in macrophages alleviates hyperinflammation and prevents immunosuppression in sepsis.

Sepsis is a leading cause of in-hospital mortality resulting from a dysregulated response to infection. Novel immunomodulatory therapies targeting macrophage metabolism have emerged as an important focus for current sepsis research. However, understanding the mechanisms underlying macrophage metabolic reprogramming and how they impact immune response requires further investigation. Here, we identify macrophage-expressed Spinster homolog 2 (Spns2), a major transporter of sphingosine-1-phosphate (S1P), as a crucial metabolic mediator that regulates inflammation through the lactate-reactive oxygen species (ROS) axis. Spns2 deficiency in macrophages significantly enhances glycolysis, thereby increasing intracellular lactate production. As a key effector, intracellular lactate promotes pro-inflammatory response by increasing ROS generation. The overactivity of the lactate-ROS axis drives lethal hyperinflammation during the early phase of sepsis. Furthermore, diminished Spns2/S1P signaling impairs the ability of macrophages to sustain an antibacterial response, leading to significant innate immunosuppression in the late stage of infection. Notably, reinforcing Spns2/S1P signaling contributes to balancing the immune response during sepsis, preventing both early hyperinflammation and later immunosuppression, making it a promising therapeutic target for sepsis.

A 3D COF constructed by interlayer crosslinking of 2D COF as cathode material for lithium-sulfur batteries.

The design and construction of three-dimensional covalent organic frameworks (3D COF) remains a major challenge, and it is necessary to explore new strategies to synthesize 3D COF with ideal structure. Here, we utilize two-dimensional covalent organic framework (2D COF) with allyl side chain to achieve interlayer crosslinking through olefin metathesis reaction, thereby constructing a 3D COF with cage-like structures. This new material named CAGE-COF has larger specific surface area and more open pore structure than the original 2D COF. The cathode material with CAGE-COF retained 78.7% of its initial capacity after 500 cycles, and the fading rate is 0.04% each cycle.

A novel coumarin derivative DBH2 inhibits proliferation and induces apoptosis of chronic myeloid leukemia cells.

With the development of tyrosine kinase inhibitor (TKI) resistance, finding the novel effective chemotherapeutic agent is of seminal importance for chronic myelogenous leukemia (CML) treatment. This study aims to find the effective anti-leukemic candidates and investigate the possible underlying mechanism. We synthesized the novel coumarin derivatives and evaluated their anti-leukemic activity. Cell viability assay revealed that compound DBH2 exhibited the potent inhibitory activity on the proliferation of CML K562 cells and TKI resistant K562 cells. Morphological observation and flow cytometry confirmed that DBH2 could selectively induce cell apoptosis and cell cycle arrest at G2/M phase of the K562 cells, which was further confirmed on the bone marrow cells from CML transgenic model mice and CD34+ bone marrow leukemic cells from CML patients. Treatments of DBH2 in combination with imatinib could prolong the survival rate of SCL-tTA-BCR/ABL transgenic model mice significantly. Quantitative RT-PCR revealed that DBH2 inhibited the expression of STAT3 and STAT5 in K562 cells, and caspase-3 knockout alleviated the DBH2 induced apoptosis. Furthermore, DBH2 could induce the expression of PARP1 and ROCK1 in K562 cells, which may play the important role in caspase-dependent apoptosis. Our results concluded that coumarin derivative DBH2 serves as a promising candidate for the CML treatment, especially in the combination with imatinib for the TKI resistant CML, and STAT/caspase-3 pathway was involved in the molecular mechanism of anti-leukemic activity of DBH2.

Advances in the biosynthesis and metabolic engineering of rare ginsenosides.

Rare ginsenosides are the deglycosylated secondary metabolic derivatives of major ginsenosides, and they are more readily absorbed into the bloodstream and function as active substances. The traditional preparation methods hindered the potential application of these effective components. The continuous elucidation of ginsenoside biosynthesis pathways has rendered the production of rare ginsenosides using synthetic biology techniques effective for their large-scale production. Previously, only the progress in the biosynthesis and biotechnological production of major ginsenosides was highlighted. In this review, we summarized the recent advances in the identification of key enzymes involved in the biosynthetic pathways of rare ginsenosides, especially the glycosyltransferases (GTs). Then the construction of microbial chassis for the production of rare ginsenosides, mainly in Saccharomyces cerevisiae, was presented. In the future, discovery of more GTs and improving their catalytic efficiencies are essential for the metabolic engineering of rare ginsenosides. This review will give more clues and be helpful for the characterization of the biosynthesis and metabolic engineering of rare ginsenosides. KEY POINTS: • The key enzymes involved in the biosynthetic pathways of rare ginsenosides are summarized. • The recent progress in metabolic engineering of rare ginsenosides is presented. • The discovery of glycosyltransferases is essential for the microbial production of rare ginsenosides in the future.