Comparative efficacy and safety of Faricimab and other anti-VEGF therapy for age-related macular degeneration and diabetic macular edema: A systematic review and meta-analysis of randomized clinical trials.

INTRODUCTION: A systematic review and meta-analysis were conducted to evaluate the efficacy and the overall safety of Faricimab compared with other anti-vascular endothelial growth factors (VEGF) therapy for neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME). MATERIALS AND METHODS: A systematic literature search of a comprehensive electronic database was performed to identify randomized clinical trials published from January 2013 to January 2023 for Faricimab in AMD and DME. Weighted mean differences and risk ratios were used to integrate the different studies. RESULTS: A total of 4 randomized controlled trials (RCTs) with 1678 AMD patients and 3 RCTs with 20 DME patients were included in the meta-analysis.In patients with AMD, a significant difference was found in the number of injections between Faricimab and other anti-VEGF therapy (MD = -2.42, 95% CI [-3.93 to -0.90], P = .002).No significant difference was found for the change in best corrected visual acuity (BVCA), central subfoveal thickness (CST), and gaining 15 or more letters. Similarly, no significant difference was found for adverse events.In patients with DME, a significant difference was observed for CST (MD = -22.41, 95% CI [-29.95 to -14.86], P < .00001) and the number of injections(MD = -0.93, 95% CI [-1.33 to -0.54], P < .00001). No significant difference was found for BVCA and gaining 15 or more letters, and no significant difference was found for adverse events. CONCLUSIONS: Comprehensive evidence confirms that Faricimab achieves non-inferior or even better CST improvement than other anti-VEGF therapies with extended dosing intervals, but more long-term follow-up studies are needed to support our conclusions.

Ultra-processed food consumption, mediating biomarkers, and risk of chronic obstructive pulmonary disease: a prospective cohort study in the UK Biobank.

Background: Ultra-processed food (UPF) is a popular supplement in the UK and other developed countries. However, whether and how UPF intake is associated with chronic obstructive pulmonary disease (COPD) remains unclear. Objective: We aimed to examine the association between UPF consumption and COPD incidence and explore the potential mediating effects of COPD-related biomarkers. Methods: This prospective cohort study included 207 002 participants without COPD at recruitment and completed 24-hour dietary recalls. UPF was defined according to the NOVA classification system. Incident COPD was ascertained using electronic hospital and mortality records. Cox regression models were used to estimate UPF consumption and the subsequent risk of COPD. Substitution analysis was performed to assess the risk of COPD by substituting UPF with an equivalent proportion of unprocessed or minimally processed food (UNPF). Mediation analyses were performed to evaluate the contribution of biomarkers related to the lipid profile, glucose metabolism, and systemic inflammation to the observed associations. Results: During a median follow-up of 13.1 (interquartile range: 12.5-13.9) years, 4670 COPD events were recorded. The adjusted hazard ratio (HR) of COPD in the highest quintile versus the lowest quintile of the UPF consumption proportion (weight percentage of the UPF) was 1.22 (95% confidence interval [CI]: 1.11-1.34). There was a 10% elevated risk of COPD incidence per SD increase in UPF intake (HR: 1.10; 95% CI: 1.08-1.13). Replacing 20% of the UNPF weight with the UPF was associated with a 13% decrease in COPD risk (95% CI: 0.84-0.91). In mediation analyses, biomarkers explained 1.0-10.1% of the association between UPF intake and COPD. Results from stratified and sensitivity analyses further support the robustness of these findings. Conclusions: Elevated UPF consumption was associated with a higher risk of COPD, and this association was primarily mediated by glucose, inflammation, and lipids, whereas substituting UNPF for UPF was associated with a decreased risk of COPD.

Association of ultra-processed food consumption with incident depression and anxiety: a population-based cohort study.

Background: Global ultra-processed food (UPF) consumption has risen rapidly. The development and prognosis of depression and anxiety remain unclarified. Herein, we aimed to examine the association between UPF consumption and the incidence and progression trajectory of depression and anxiety. Methods: In our study, participants were recruited between 2006 and 2010. UPF consumption was expressed as UPF servings, energy ratio, and weight ratio. The relationships between UPF consumption and depression or anxiety were assessed using the Cox proportional hazards model. Multi-state models were used to explore the association between UPF consumption and the risks of all transitions from a healthy state to depression or anxiety and then to all-cause mortality. Results: Among the 183 474 participants, 5453 were diagnosed with depression and 6763 with anxiety during the follow-up of 13.1 years. The participants in the highest quartile (Q4) of UPF servings, energy ratio, and weight ratio had an increased risk of depression compared to those in the lowest quartile (Q1), with hazard ratios (HRs) and 95% confidence intervals [CIs] of 1.22 (1.13-1.31), 1.13 (1.05-1.22), and 1.26 (1.17-1.36), respectively. Similarly, participants in Q4 of UPF consumption had a higher risk of anxiety, with HRs (95% CIs) of 1.13 (1.06-1.21), 1.13 (1.05-1.21), and 1.11 (1.04-1.19), compared to those in Q1. The study also found a significant association between UPF consumption and all-cause mortality, which disappeared for participants with depression or anxiety. Conclusions: Our findings revealed that UPF consumption is associated with depression or anxiety.

Flexible and Antifreezing Fiber-Shaped Solid-State Zinc-Ion Batteries with an Integrated Bonding Structure.

Fiber-shaped solid-state zinc-ion battery (FZIB) is a promising candidate for wearable electronic devices, but challenges remain in terms of mechanical stability and low temperature tolerance. Herein, we design and fabricate a FZIB with an integrated device structure through effective incorporation of the active electrode materials with a carbon fiber rope (CFR) and a gel polymer electrolyte. The gel polymer electrolyte incorporated with ethylene glycol (EG) and graphene oxide (GO) endows the FZIB with a high Zn stripping/plating efficiency under extreme low temperature conditions. A high power density of 1.25 mW cm-1 and large energy density of 0.1752 mWh cm-1 are obtained. In addition, a high capacity retention of 91% after 2000 continuous bending cycles is achieved. Furthermore, the discharge capacity is fairly retained at more than 22% even at the low temperature of -20 °C. Toward practical applications, the FZIB integrated into textiles to power electronic products is demonstrated.

All-Printed 3D Solid-State Rechargeable Zinc-Air Microbatteries.

Lightweight, compact, integrated, and miniaturized energy devices are under high pursuit for portable and wearable electronics. However, improving the energy density per area still remains a long-standing challenge. Herein, we report the design and fabrication of a solid-state zinc-air microbattery (ZAmB) by a facile 3D direct printing technique. The interdigital electrodes, gel electrolyte, and encapsulation frame are all printed with a customized design by optimzing the composition of the printing inks to obtain the best battery performance. Multiple layers of interdigital electrodes are sequentially printed with a fine overlap to achieve an ultrahigh thickness of 2.5 mm for a remarkably increased specific areal energy of up to 77.2 mWh cm-2. To meet the practical powering requirements for different output voltages and currents, battery modules consisting of individual ZAmBs connected in series or parallel or a combination of the two are printed with a facile integration to external loads. Powering of LEDs, digital watch, and a miniature rotary motor and even charging of a smartphone by the printed ZAmB modules are successfully demonstrated. The versatile 3D direct printing technique enables the fabricated ZAmBs with an adjustable form factor and integration capability with other electronics, paving the way for exploring new energy systems with diverse structures and extended functionalities.

Flavonoids from the Roots of Sophora flavescens and Their Potential Anti-Inflammatory and Antiproliferative Activities.

The phytochemical investigation of the roots of the traditional Chinese medicinal plant Sophora flavescens led to the isolation of two novel prenylflavonoids with an unusual cyclohexyl substituent instead of the common aromatic ring B, named 4',4'-dimethoxy-sophvein (17) and sophvein-4'-one (18), and 34 known compounds (1-16, 19-36). The structures of these chemical compounds were determined by spectroscopic techniques, including 1D-, 2D-NMR, and HRESIMS data. Furthermore, evaluations of nitric oxide (NO) production inhibitory activity against lipopolysaccharide (LPS)-treated RAW264.7 cells indicated that some compounds exhibited obvious inhibition effects, with IC50 ranged from 4.6 ± 1.1 to 14.4 ± 0.4 µM. Moreover, additional research demonstrated that some compounds inhibited the growth of HepG2 cells, with an IC50 ranging from 0.46 ± 0.1 to 48.6 ± 0.8 µM. These results suggest that flavonoid derivatives from the roots of S. flavescens can be used as a latent source of antiproliferative or anti-inflammatory agents.

Recent Development of Self-Powered Tactile Sensors Based on Ionic Hydrogels.

Hydrogels are three-dimensional polymer networks with excellent flexibility. In recent years, ionic hydrogels have attracted extensive attention in the development of tactile sensors owing to their unique properties, such as ionic conductivity and mechanical properties. These features enable ionic hydrogel-based tactile sensors with exceptional performance in detecting human body movement and identifying external stimuli. Currently, there is a pressing demand for the development of self-powered tactile sensors that integrate ionic conductors and portable power sources into a single device for practical applications. In this paper, we introduce the basic properties of ionic hydrogels and highlight their application in self-powered sensors working in triboelectric, piezoionic, ionic diode, battery, and thermoelectric modes. We also summarize the current difficulty and prospect the future development of ionic hydrogel self-powered sensors.

A highly stretchable and ultra-sensitive strain sensing fiber based on a porous core-network sheath configuration for wearable human motion detection.

Functional fibers have attracted much research attention due to their potential application in developing advanced electronic textiles for wearable devices. However, challenges still exist in preparing high-performance fiber-shaped sensors with superior flexibility and stretchability while achieving a high sensitivity and a wide detection range. Herein, we propose the design and fabrication of an ultra-flexible and super-elastic fiber-shaped strain sensor via a facile combining approach of wet-spinning and dip-coating. The sensor adopts a core-sheath configuration of liquid metal droplets dispersed in porous thermoplastic polyurethane as a substrate core and a carbon nanotube intertwined network embedding silver nanowires as a strain sensitive sheath. By taking advantage of both the composition of multiple functional materials and the design of a microstructured device configuration, the developed fiber-shaped sensor exhibits an ultrahigh sensitivity (maximum gauge factor of 7336.1), an extremely large workable strain range (500%), a low strain detection limit (0.5%), a fast response time (200 ms) and good stability (10 000 cycles). In addition, the sensor is temperature insensitive, inert under harsh solution conditions, degradable and recyclable. Intriguingly, the fiber-shaped sensor can be used to detect various human motions and gestures by directly attaching to skins or elaborately weaving into textiles, demonstrating its great potential in human healthcare monitoring and human-machine interactions.

A bivalent cyclic RGD-siRNA conjugate enhances the antitumor effect of apatinib via co-inhibiting VEGFR2 in non-small cell lung cancer xenografts.

The vascular endothelial growth factor receptor 2 (VEGFR2) is considered to be a pivotal target for anti-tumor therapy against angiogenesis of non-small cell lung cancer (NSCLC). However, effective and low-toxicity targeted therapies to inhibit VEGFR2 are still lacking. Here, biRGD-siVEGFR2 conjugate comprising murine VEGFR2 siRNA and [cyclo(Arg-Gly-Asp-D-Phe-Lys)-Ahx]2-Glu-PEG-MAL (biRGD) peptide which selectively binds to integrin αvß3 receptors expressing on neovascularization endothelial cell was synthesized. The anti-tumor activity and renal toxicity of biRGD-siVEGFR2 or its combination therapy with low-dose apatinib were investigated on NSCLC xenografts. The immunogenicity of biRGD-siVEGFR2 was also evaluated in C57BL/6J mice. In vivo, intravenously injected biRGD-siVEGFR2 substantially inhibited NSCLC growth with a marked reduction of vessels and a down-regulation of VEGFR2 in tumor tissue. Furthermore, biRGD-siVEGFR2 in combination with low-dose apatinib achieved powerful anti-tumor effect with less nephrotoxicity compared with the regular dose of apatinib. Besides, no obvious immunogenicity of biRGD-siVEGFR2 was found. These findings demonstrate that biRGD-siVEGFR2 conjugate can be used as a new candidate for the treatment of NSCLC and its combination therapy with apatinib may also provide a novel strategy for cancer treatment in clinic.

Ubiquitination and degradation of NF90 by Tim-3 inhibits antiviral innate immunity.

Nuclear factor 90 (NF90) is a novel virus sensor that serves to initiate antiviral innate immunity by triggering stress granule (SG) formation. However, the regulation of the NF90-SG pathway remains largely unclear. We found that Tim-3, an immune checkpoint inhibitor, promotes the ubiquitination and degradation of NF90 and inhibits NF90-SG-mediated antiviral immunity. Vesicular stomatitis virus (VSV) infection induces the up-regulation and activation of Tim-3 in macrophages, which in turn recruit the E3 ubiquitin ligase TRIM47 to the zinc finger domain of NF90 and initiate a proteasome-dependent degradation via K48-linked ubiquitination at Lys297. Targeted inactivation of Tim-3 enhances the NF90 downstream SG formation by selectively increasing the phosphorylation of protein kinase R and eukaryotic translation initiation factor 2α, the expression of SG markers G3BP1 and TIA-1, and protecting mice from VSV challenge. These findings provide insights into the crosstalk between Tim-3 and other receptors in antiviral innate immunity and its related clinical significance.

Tim-3 Promotes Listeria monocytogenes Immune Evasion by Suppressing Major Histocompatibility Complex Class I.

BACKGROUND: T-cell immunoglobulin and mucin protein 3 (Tim-3) is an immune checkpoint inhibitor that has therapeutic implications for many tumors and infectious diseases. However, the mechanisms by which Tim-3 promotes immune evasion remain unclear. METHODS: In this study, we demonstrated that Tim-3 inhibits the expression of major histocompatibility complex class I (MHC-I) in macrophages at both the messenger ribonucleic acid and protein levels by inhibiting the STAT1-NLRC5 signaling pathway. RESULTS: As a result, MHC-I-restricted antigen presentation by macrophages was inhibited by Tim-3 both in vitro and in a Listeria monocytogenes infection model in vivo. Systemic overexpression of Tim-3 or specific knockout of Tim-3 in macrophages significantly attenuated or enhanced CD8+ T-cell activation and infection damage in L monocytogenes-infected mice, respectively. CONCLUSIONS: Thus, we identified a new mechanism by which Tim-3 promotes L monocytogenes immune evasion. Further studies on this pathway might shed new light on the physio-pathological roles of Tim-3 and suggest new approaches for intervention.

A Freestanding Single-Wall Carbon Nanotube Film Decorated with N-Doped Carbon-Encapsulated Ni Nanoparticles as a Bifunctional Electrocatalyst for Overall Water Splitting.

Noble-metal free, cost-effective, and highly stable catalysts with efficient activity for both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) have attracted tremendous research interest in recent years. Here, a flexible, self-standing hybrid film comprising a N-doped single-wall carbon nanotube (SWCNT) network on which are anchored Ni nanoparticles encapsulated by a monolayer of N-doped carbon (NCNi) is reported. The films are prepared by floating catalyst chemical vapor deposition followed by NH3 treatment. The material obtained at optimum conditions shows excellent bifunctional electrocatalytic activity in alkaline media with low overpotentials of 190 and 270 mV for HER and OER, respectively, to reach a current density of 10 mA cm-2. A current density of 10 mA cm-2 at 1.57 V is achieved when this freestanding and binder-free rod-shaped NCNi/SWCNT assembly is used as cathode and anode in 1 m KOH solution for overall water splitting, presenting one of the best values reported to date.

Protective effect of Gelofusine against cRGD-siRNA-induced nephrotoxicity in mice.

Based on successful targeting to the αvß3 integrin of cyclic arginine-glycine-aspartic acid (cRGD), cRGD-conjugated small interfering RNA (siRNA) exhibits tumor targeting and has become a new treatment strategy for solid tumors. However, the nephrotoxicity caused by its renal retention limits its clinical application. Here, we evaluated the protective effect of Gelofusine against cRGD-conjugated siRNA-induced nephrotoxicity in mice. Male Kunming mice (six per group) were either co-injected with Gelofusine and cRGD-siRNA or injected with cRGD-siRNA alone. After administration of these treatments five times, creatinine and blood urea nitrogen (BUN) levels were determined. Hematoxylin-eosin staining (HE staining) and transferase dUTP nick end labeling (TUNEL) analysis were used to compare the difference in renal damage between the groups. Additionally, fluorescence imaging was used to observe the distribution of cRGD-siRNA in vivo. The group co-injected with Gelofusine and cRGD-siRNA displayed lower creatinine and BUN levels than the cRGD-siRNA-alone group and showed less renal damage upon HE staining and TUNEL analysis. Gelofusine decreased the retention time and accelerated the elimination of cRGD-siRNA from the organs, as observed in the fluorescence images. These data indicate that Gelofusine significantly increased the excretion of cRGD-conjugated siRNA and reduced the associated renal damage.

[Small interfering RNA-mediated programmed cell death-ligand 1 silencing in human glioma cells enhances human CD8+ T lymphocyte cytotoxicity in vitro].

OBJECTIVE: To investigate the effect of small interfering RNA (siRNA)-mediated silencing of programmed cell deathligand 1 (PD-L1) in human glioma cells on the cytotoxicity of human CD8+T lymphocytes against the modified tumor cells. METHODS: A siRNA sequence targeting PD-L1 gene was designed and transfected into human glioma U87 MG cells via lipofectamine 2000, and the gene silencing effect was validated using RT-qPCR, Western blotting, and flow cytometry. The transfected cells were co-cultured with human CD8+T lymphocytes, and the apoptosis of the tumor cells was analyzed with flow cytometry. RESULTS: The siRNA sequence showed strong PD-L1 gene-silencing effect at both mRNA and protein levels in U87 MG cells. Compared with the control cells, the transfected U87 MG cells showed significantly increased vulnerability to the cytotoxicity of human CD8+T cells and an obvious reduction of proliferative activity in the co-culture (P < 0.05). CONCLUSIONS: Transfection of human glioma U87 MG cells with the specific siRNA targeting PD-L1 obviously enhances the toxicity of human T lymphocytes in the co-culture.

Nitrogen-Superdoped 3D Graphene Networks for High-Performance Supercapacitors.

An N-superdoped 3D graphene network structure with an N-doping level up to 15.8 at% for high-performance supercapacitor is designed and synthesized, in which the graphene foam with high conductivity acts as skeleton and nested with N-superdoped reduced graphene oxide arogels. This material shows a highly conductive interconnected 3D porous structure (3.33 S cm-1 ), large surface area (583 m2 g-1 ), low internal resistance (0.4 Ω), good wettability, and a great number of active sites. Because of the multiple synergistic effects of these features, the supercapacitors based on this material show a remarkably excellent electrochemical behavior with a high specific capacitance (of up to 380, 332, and 245 F g-1 in alkaline, acidic, and neutral electrolytes measured in three-electrode configuration, respectively, 297 F g-1 in alkaline electrolytes measured in two-electrode configuration), good rate capability, excellent cycling stability (93.5% retention after 4600 cycles), and low internal resistance (0.4 Ω), resulting in high power density with proper high energy density.

Preparation of metallic single-wall carbon nanotubes by selective etching.

We report the bulk synthesis of a sample with a high concentration of metallic single-wall carbon nanotubes (m-SWCNTs) using a modified floating catalyst chemical vapor deposition method with methane as the carbon precursor. By tuning experimental parameters, such as species and flux of carrier gases, catalyst concentration, growth temperature, etc., small-diameter semiconducting SWCNTs (s-SWCNTs) and large-diameter m-SWCNTs were obtained. Using identical growth conditions, at a temperature of 1000 °C, it was found that the addition of hydrogen as an etchant gas resulted in the preferential removal of the smaller diameter s-SWCNTs. As a result, a sample enriched with large-diameter metallic SWCNTs was obtained. The self-assembled fishnet-like m-SWCNT network showed excellent optical transparency and electrical conductivity.

[Changes of eye signs in chronic hepatitis B patients with blood stasis syndrome].

OBJECTIVE: To study the characteristics of eye signs in chronic hepatitis B patients with blood stasis syndrome and the association between blood stasis syndrome and eye signs. METHODS: A total of 126 patients with chronic hepatitis B were randomly divided into four groups: non-blood stasis group, and mild, moderate and severe blood stasis groups. The changes of eye signs in the four groups were tested and compared. RESULTS: There were significant differences in scores of blood stasis and eye signs among the four groups (P<0.05 or P<0.01). The changes of eye signs in chronic hepatitis B patients with blood stasis syndrome were different with those with non-blood stasis syndrome. There were no significant differences in each item of the eye signs among the four groups (P>0.05). CONCLUSION: The eye signs of blood stasis syndrome are applicable, objective and convenient for diagnosing blood stasis syndrome in patients with chronic hepatitis B.