The impact of cathepsins on liver hepatocellular carcinoma: Insights from genetic and functional analyses.

Liver Hepatocellular Carcinoma (LIHC), ranked as the second deadliest cancer globally, poses a major health challenge because of its widespread occurrence and poor prognosis. The mechanisms underlying LIHC development and progression remain unclear. Cathepsins are linked to tumorigenesis in other cancers, but their role in LIHC is underexplored. This study employed integrative analyses, including Mendelian Randomization (MR), bulk RNA-sequencing (bulk-seq), single-cell RNA sequencing (scRNA-seq), immunohistochemical (IHC) analysis, and cellular experiments with siRNA technology, to investigate the role of cathepsin E (CTSE) in LIHC. MR analysis identified CTSE as a factor associated with increased LIHC risk. Prognostic analysis using TCGA data showed that higher CTSE levels are linked to poorer survival, establishing CTSE as an independent prognostic risk factor. Integrative transcriptome analysis revealed close relation of CTSE to the extracellular matrix. scRNA-seq from TISCH2 demonstrated that CTSE is predominantly expressed in malignant LIHC cells. IHC confirmed higher CTSE expression in LIHC tissues compared to peritumoral tissues. Functional assays, such as qRT-PCR, Western blot, cell proliferation, and colony formation experiments, demonstrated that siRNA-mediated CTSE knockdown in HepG2 and Huh7 cell lines notably suppressed cell proliferation and altered the FAK/Paxillin/Akt signaling cascade. This research enhances our comprehension of LIHC development, emphasizing CTSE as a promising prognostic marker and potential therapeutic target. Inhibiting CTSE could slow the progression of LIHC, presenting novel opportunities for therapeutic approaches.

Cutting-Edge Progress in Aqueous Zn-S Batteries: Innovations in Cathodes, Electrolytes, and Mediators.

Rechargeable aqueous zinc-sulfur batteries (AZSBs) are emerging as prominent candidates for next-generation energy storage devices owing to their affordability, non-toxicity, environmental friendliness, non-flammability, and use of earth-abundant electrodes and aqueous electrolytes. However, AZSBs currently face challenges in achieving satisfied electrochemical performance due to slow kinetic reactions and limited stability. Therefore, further research and improvement efforts are crucial for advancing AZSBs technology. In this comprehensive review, it is delved into the primary mechanisms governing AZSBs, assess recent advancements in the field, and analyse pivotal modifications made to electrodes and electrolytes to enhance AZSBs performance. This includes the development of novel host materials for sulfur (S) cathodes, which are capable of supporting higher S loading capacities and the refinement of electrolyte compositions to improve ionic conductivity and stability. Moreover, the potential applications of AZSBs across various energy platforms and evaluate their market viability based on recent scholarly contributions is explored. By doing so, this review provides a visionary outlook on future research directions for AZSBs, driving continuous advancements in stable AZSBs technology and deepening the understanding of their charge-discharge dynamics. The insights presented in this review signify a significant step toward a sustainable energy future powered by renewable sources.

Cost-effectiveness analysis of direct oral anticoagulants versus low-molecular-weight heparin and no thromboprophylaxis in primary prevention of cancer-associated venous thromboembolism in China.

Background and objective: Cancer-associated venous thromboembolism (CAVTE) is a preventable, life-threatening complication with a considerable morbidity and mortality. Primary venous thromboembolism (VTE) prophylaxis is currently recommended; however, the health and economic benefits have not been evaluated and compared in China. This study aimed to assess and compare the cost-effectiveness of anticoagulants in primary CAVTE prevention among cancer patients in China. Methods: A Markov model with a 5-year horizon was established to evaluate the costs and effectiveness of direct oral anticoagulants (DOACs) compared to low-molecular-weight heparins (LMWHs) and no prevention in primary prophylaxis of CAVTE in China. Key clinical outcomes were obtained from the available clinical trials, comparing DOACs (rivaroxaban and apixaban) with LMWHs or with no thromboprophylaxis. Utility and the cost inputs were all obtained from the published literature or local data with public sources. The total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated as the main endpoints of the modal for each strategy. The assessment of uncertainty was performed involving deterministic sensitivity analysis and probabilistic sensitivity analysis (PSA). Impact of time horizon, generic drug price, and individual DOACs were assessed in scenario and subgroup analyses. Results: Primary prophylaxis using DOACs were projected to yield 1.866 QALYs at a cost of $3,287.893, resulting in the ICERs of $12,895.851 (DOACs vs. no-thromboprophylaxis) and $43,613.184/QALYs (LMWHs vs. DOACs). Sensitivity analysis revealed that ICER was sensitive to the VTE and bleeding risk, drug cost of anticoagulants, self-payment ratio, and overall death rate of cancer. Probabilistic sensitivity analysis showed that DOACs and LMWHs had a 48% and 45% probability of being cost-effective at a 5-year time horizon, respectively. When the time horizon extended to 10 years, DOACs achieved a cost-effective probability of 43%. Among individual DOACs, apixaban was found to be the preferred strategy in VTE prevention due to its incremental health gain with an acceptable cost increase. Conclusion: Primary thromboprophylaxis with DOACs was cost-effective in cancer patients at a willing-to-pay (WTP) threshold of $37,125.24/QALY in China. Cancer death rate, risk of VTE and major bleeding, and the drug cost assumed greater relevance and importance in the decision-making process for primary thromboprophylaxis in cancer.

Efficacy and safety of hepatic arterial infusion chemotherapy combined with donafenib in the treatment of unresectable hepatocellular carcinoma.

OBJECTIVE: This study aimed at ascertaining the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with donafenib versus HAIC alone in the treatment of unresectable hepatocellular carcinoma (HCC). METHODS: Seventy HCC patients were enrolled for our study, and they were randomized by simple randomization using computer-generated random numbers into two groups: control group and observation group. Regular follow-up reviews were conducted to assess the efficacy of treatments. The levels of apoptotic factors, the levels of hepatic fibrosis indices, the levels of serum tumor vascular factors and tumor markers, and the occurrence of adverse reactions in the two groups were recorded and compared. RESULTS: Disease control rate, objective response rate, and progression-free survival (PFS) of patients in the observation group were higher in contrast to the control group. After 12 weeks of treatment, lower mRNA expression of c-mesenchymal-epithelial transition factor, telomerase, and Fas Ligand and higher mRNA expression of Fas and Caspase-3 were observed in HCC tissues of the observation group versus the control group (p < 0.05); lower detection values of serum laminin, hyaluronic acid, collage type IV, vascular endothelial growth factor receptor 2, and alpha-fetal protein (AFP) were noted in HCC patients of the observation group in comparison to the control group (p < 0.05); there was no difference in the incidence of adverse reactions between the two groups. CONCLUSION: Donafenib combined with HAIC in the treatment of unresectable HCC patients can notably reduce serum AFP levels, improve hepatic fibrosis, enhance short-term efficacy, prolong PFS, and have a favorable safety profile.

Exploring genetic associations in systemic lupus erythematosus through Mendelian randomization: implications for novel biomarkers and therapeutic targets.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a significant health burden. There is an essential need for novel biomarkers and therapeutic targets to improve diagnosis and management. Mendelian randomization (MR) was applied to explore causal links between SLE and various biomarkers like immune cells, metabolites, and inflammatory cytokines using multiple databases. Initially, biomarkers significantly associated with SLE were identified. Bidirectional MR helped clarify these relationships, and a two-step mediation MR examined their effects on SLE risk. Intersection analysis was used to identify biomarkers with consistent effects across datasets. Four biomarkers were identified as having significant associations with SLE risk: 1-palmitoyl-2-arachidonoyl-GPI levels [odds ratio (OR), 1.379; 95% confidence interval (CI), 1.180 to 1.613; FDR, 0.046], IL-17A levels (OR, 2.197; 95% CI, 1.412 to 3.418; FDR, 0.044), N-acetyl-aspartyl-glutamate (NAAG) levels (OR, 0.882; 95% CI, 0.831 to 0.936; FDR, 0.030), and ribitol levels (OR, 0.743; 95% CI, 0.644 to 0.857; FDR, 0.012). Bidirectional MR showed an inverse effect of NAAG on IL-17A levels (OR, 0.978; 95% CI, 0.962 to 0.994; p = 0.006). Mediation analysis indicated that NAAG influenced SLE risk both directly (beta = - 0.108) and indirectly through IL-17A (beta = - 0.018), highlighting the potential mediating role of IL-17A. After expanding the significance criteria to p < 0.05, intersection analysis across multiple datasets revealed 29 biomarkers with consistent beta directions, including 19 potential risk factors (beta > 0) and 10 protective factors (beta < 0) for SLE. This research has revealed significant genetic associations with SLE and demonstrated that IL-17A mediates the relationship between NAAG levels and SLE risk, highlighting potential new targets for personalized therapeutic interventions. Key Points • This study employs MR to identify significant genetic associations between various biomarkers and SLE, providing novel insights into potential biomarkers and therapeutic targets. • Four key biomarkers were identified as significantly associated with SLE risk: 1-palmitoyl-2-arachidonoyl-GPI, IL-17A, N-acetyl-aspartyl-glutamate (NAAG), and ribitol. • The findings suggest that NAAG levels have a protective effect against SLE, partly mediated through IL-17A, indicating a complex interplay between these biomarkers in the pathogenesis of SLE. • Intersectional analysis across multiple datasets revealed 29 biomarkers with consistent effects on SLE risk, highlighting new directions for future research and potential personalized therapeutic strategies.

The phase behavior of CO2 injection in shale reservoirs with nano-pores.

The main purpose of this paper is to study the solubility of CO2 in oil and water phase under high temperature and pressure. Firstly, CO2-crude oil PVT experiments were carried out to determine the physical parameters of the reservoir fluid in the study field in order to clarify the interaction mechanism of CO2 with the crude oil. Secondly, the solubility of CO2 in the reservoir fluid under different pores and the minimum mixed-phase pressure of the CO2-crude oil system were calculated by the improved Peng-Robinson equation of state. In this paper, the effects of nano-pores limitation on CO2 solubility were studied. The results show that pressure increase is favorable to CO2 dissolution, the solubility increases with the increase of the oil-water ratio. CO2 solubility decreases with temperature increase. The greater the mineralization of formation water, the lower the CO2 solubility. Nanopore confinement causes the phase envelope to contract and the minimum mixed-phase pressure to decrease. When the pore radius is smaller, the restriction of the phase envelope is stronger. In this paper, the minimum mixing pressure of crude oil and carbon dioxide is reduced from 31.25 MPa at 50 nm to 21.25 MPa at 5 nm, thus it is beneficial for enhanced oil recovery (CO2-EOR). Nanopore confinement favors CO2 to enhance shale oil recovery. The results of this study are critical to evaluate the effect of CO2 sequestration, solubility and phase behavior changes of CO2 in shale reservoirs with nano-pores.

Research on the mechanism of sea buckthorn leaf Fu tea in the treatment of hyperlipidemia.

Background: Hyperlipidemia (HLP) presents a significant challenge to global public health. Mounting evidence suggests that statins, the recommended first-line lipid-lowering agents, have significant adverse effects. Consequently, the quest for natural and efficacious alternative therapies is steadily emerging as a research priority for HLP prevention and treatment. Consumption of tea, which is rich in diverse biologically active compounds with the capacity to regulate lipid metabolism and combat obesity, has emerged as a promising alternative therapy. Sea buckthorn leaves are rich in a multitude of biologically active substances, have a hypolipidemic effect, and can be used as a raw material for tea because of their unique flavor. There is a suggestion that combining Aspergillus cristatus with tea could modify or boost the lipid-lowering active compounds present in tea, thereby increasing its efficacy in regulating lipid metabolism. Results: Sea Buckthorn Leaf Fu Tea (SBLFT) was obtained by fermentation when sea buckthorn leaves contained 42 % moisture, inoculated with Aspergillus cristatus 0.2 mL/g, and incubated for 8 d at constant temperature. Animal experiments demonstrated that SBLFT significantly inhibited body weight gain in HLP rats and reduced lipid content and serum oxidative stress. In addition, liver tissue sections and functional indices showed that SBLFT can improve liver morphology and function abnormalities. Reverse transcription-polymerase chain reaction results indicated that the expression of Liver kinase B1 (LKB1), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), acetyl CoA carboxylase 1 (ACC1), and sterol-regulatory element binding protein-1 (SREBP1c) gene related to lipid metabolism was altered. Conclusion: SBLFT improved HLP, specifically via promoting the expression of LKB1 in the liver of HLP rats, activating AMPK, and inhibiting ACC1 and SREBP1c expression, resulting in the inhibition of fatty acid and triglyceride synthesis-related enzymes at the transcriptional level.

Relationship between preoperative psychological stress and short-term prognosis in elderly patients with femoral neck fracture.

BACKGROUND: Older adults are at high risk of femoral neck fractures (FNFs). Elderly patients face and adapt to significant psychological burdens, resulting in different degrees of psychological stress response. Total hip replacement is the preferred treatment for FNF in elderly patients; however, some patients have poor postoperative prognoses, and the underlying mechanism is unknown. We speculated that the postoperative prognosis of elderly patients with FNF may be related to preoperative psychological stress. AIM: To explore the relationship between preoperative psychological stress and the short-term prognosis of elderly patients with FNF. METHODS: In this retrospective analysis, the baseline data, preoperative 90-item Symptom Checklist score, and Harris score within 6 months of surgery of 120 elderly patients with FNF who underwent total hip arthroplasty were collected. We analyzed the indicators of poor short-term postoperative prognosis and the ability of the indicators to predict poor prognosis and compared the correlation between the indicators and the Harris score. RESULTS: Anxiety, depression, garden classification of FNF, cause of fracture, FNF reduction quality, and length of hospital stay were independent influencing factors for poor short-term postoperative prognoses in elderly patients with FNF (P < 0.05). The areas under the curve for anxiety, depression, and length of hospital stay were 0.742, 0.854, and 0.749, respectively. The sensitivities of anxiety, depression, garden classification of FNF, and prediction of the cause of fracture were 0.857, 0.786, 0.821, and 0.821, respectively. The specificities of depression, FNF quality reduction, and length of hospital stay were the highest at 0.880, 0.783, and 0.761, respectively. Anxiety, depression, and somatization scores correlated moderately with Harris scores (r = -0.523, -0.625, and -0.554; all P < 0.001). CONCLUSION: Preoperative anxiety, depression, and somatization are correlated with poor short-term prognosis in elderly patients with FNF and warrant consideration.

Yiqi Jiedu Huayu decoction inhibits precancerous lesions of chronic atrophic gastritis by inhibiting NLRP3 inflammasome-mediated pyroptosis.

BACKGROUND: Chronic atrophic gastritis (CAG) is a prevalent chronic gastritis usually accompanied by precancerous lesions such as intestinal metaplasia and dysplasia. The increasing application of traditional Chinese medicine in CAG treatment has shown promising results with low side effects and significant efficacy. AIM: To investigate the pharmacological effects of Yiqi Jiedu Huayu decoction (YJHD) on precancerous lesions of CAG. METHODS: A CAG rat model was established by Helicobacter pylori bacteria solution combined with N-methyl-N'-nitro-N-nitrosoguanidine. Histopathological measurements were conducted by hematoxylin-eosin and alcian blue and periodic acid-Schiff staining. Serum levels of inflammatory factors and gastric mucosal-related factors were examined using enzyme-linked immunosorbent assay. Protein and mRNA levels were quantified via western blot and quantitative real-time polymerase chain reaction analysis, respectively. Molecular interaction was verified by chromatin immunoprecipitation (ChIP) assay. RESULTS: YJHD greatly attenuated pathological changes in the gastric mucosa and precancerous lesions in CAG rats. Meanwhile, YJHD treatment reduced serum levels of inflammatory factors [interleukin (IL)-6, tumor necrosis factor-α and C-reactive protein] and increased serum levels of gastric mucosal-related factors (gastrin, pepsin, somatostatin and prostaglandin E2) in CAG rats. In addition, YJHD administration suppressed NLRP3 inflammasome-mediated cell pyroptosis, as well as the activation of TLR4/NF-κB and IL-6/STAT3 signaling pathways. Mechanically, ChIP experiments confirmed that NLRP3 transcription was regulated by TLR4/NF-κB and IL-6/STAT3 signaling. CONCLUSION: Taken together, YJHD alleviated NLRP3 inflammasome formation and pyroptosis of epithelial cells in CAG, potentially through the inactivation of TLR4/NF-κB and IL-6/STAT3 pathways.

One-Step Synthesis of Graphene-Covered Silver Nanowires with Enhanced Stability for Heating and Strain Sensing.

Solution-processed silver nanowire (AgNW) networks have been considered as promising electrode candidates for next-generation electronic devices. However, they suffer from poor thermal and electrical stability and low mechanical properties, hindering their practical applications. In this work, graphene nanosheets are successfully introduced into AgNW via a facile one-step solvothermal process. Benefiting from increased conductive paths, the resultant AgNW/graphene films exhibit high electrical conductivity. More importantly, the interlocking NW morphology can be maintained under high temperature and applied voltage due to suppressed Ag migration, which is enabled by the introduction of graphene. This feature leads to enhanced thermal and electrical stability, making them suitable for use as transparent heaters. Furthermore, the composite films present excellent mechanical performance, and negligible resistance change is observed after 10 000 repeated bending cycles. To demonstrate their feasibility toward sensor applications, sandwiched strain sensors are designed, which can endure larger tensile strains and show higher sensitivity and repeatability compared with pure AgNW-based device. Furthermore, various hand gestures can be easily recognized by the resultant sensors based on unique combinations of sensing response. This work not only provides a low-cost method to realize large-scale synthesis of AgNW/graphene composites but also offers guidance to prepare high-performance electrodes for advanced electronics.

Synergistic barium titanate/MXene composite as a high-performance piezo-photocatalyst for efficient dye degradation.

Piezo-photocatalysis combines photocatalysis and piezoelectric effects to enhance catalytic efficiency by creating an internal electric field in the photocatalyst, improving carrier separation and overall performance. This study presents a high-performance piezo-photocatalyst for efficient dye degradation using a synergistic barium titanate (BTO)-MXene composite. The composite was synthesized via a facile method, combining the unique properties of BTO nanoparticles with the high conductivity of MXene. The structural and morphological analysis confirmed the successful formation of the composite, with well-dispersed BTO nanoparticles on the MXene surface. The piezo-photocatalytic activity of the composite was evaluated using a typical dye solution (Rhodamine B: RhB) under ultraviolet irradiation and mechanical agitation. The results revealed a remarkable enhancement in dye degradation (90 % in 15 min for piezo-photocatalysis) compared to individual stimuli (58.2 % for photocatalysis and 95.8 % in 90 min for piezocatalysis), highlighting the synergistic effects between BTO and MXene. The enhanced catalytic performance was attributed to the efficient charge separation and transfer facilitated by the composite's structure, leading to increased reactive species generation and dye molecule degradation. Furthermore, the composite exhibited excellent stability and reusability, showcasing its potential for practical applications in wastewater treatment. Overall, this work represents a promising strategy for designing high-performance synergistic catalysts, addressing the pressing need for sustainable solutions in environmental remediation.

WhiB-like proteins: Diversity of structure, function and mechanism.

The WhiB-Like (Wbl) proteins are a large family of iron-sulfur (Fe-S) cluster-containing transcription factors exclusively found in the phylum Actinobacteria, including the notable genera like Mycobacteria, Streptomycetes and Corynebacteria. These proteins play pivotal roles in diverse biological processes, such as cell development, redox stress response and antibiotic resistance. Members of the Wbl family exhibit remarkable diversity in their sequences, structures and functions, attracting great attention since their first discovery. This review highlights the most recent breakthroughs in understanding the structural and mechanistic aspects of Wbl-dependent transcriptional regulation.

A Multiscale Connected UNet for the Segmentation of Lung Cancer Cells in Pathology Sections Stained Using Rapid On-Site Cytopathological Evaluation.

Lung cancer is an increasingly serious health problem worldwide, and early detection and diagnosis are crucial for successful treatment. With the development of artificial intelligence and the growth of data volume, machine learning techniques can play a significant role in improving the accuracy of early detection in lung cancer. This study proposes a deep learning-based segmentation algorithm for rapid on-site cytopathological evaluation (ROSE) to enhance the diagnostic efficiency of endobronchial ultrasound-guided transbronchial needle aspiration biopsy (EBUS-TBNA) during surgery. By utilizing the CUNet3+ network model, cell clusters, including cancer cell clusters, can be accurately segmented in ROSE-stained pathological sections. The model demonstrated high accuracy, with an F1-score of 0.9604, recall of 0.9609, precision of 0.9654, and accuracy of 0.9834 on the internal testing data set. It also achieved an area under the receiver-operating characteristic curve of 0.9972 for cancer identification. The proposed algorithm saved time for on-site diagnosis, improved EBUS-TBNA efficiency, and outperformed classical segmentation algorithms in accurately identifying lung cancer cell clusters in ROSE-stained images. It effectively reduced over-segmentation, decreased network parameters, and enhanced computational efficiency, making it suitable for real-time patient evaluation during surgical procedures.

Enhanced Piezocatalytic Performance of Li-doped BaTiO3 Through a Facile Sonication-Assisted Precipitation Approach.

Piezocatalysis-induced dye degradation has garnered significant attention as an effective method for addressing wastewater treatment challenges. In our study, we employed a room-temperature sonochemical method to synthesize piezoelectric barium titanate nanoparticles (BaTiO3: BTO) with varying levels of Li doping. This approach not only streamlined the sample preparation process but also significantly reduced the overall time required for synthesis, making it a highly efficient and practical method. One of the key findings was the exceptional performance of the Li-doped BTO nanoparticles. With 20 mg of Li additive, we achieved 90 % removal of Rhodamine B (RhB) dye within a relatively short timeframe of 150 minutes, all while subjecting the sample to ultrasonic vibration. This rapid and efficient dye degradation was further evidenced by the calculated kinetic rate constant, which indicated seven times faster degradation rate compared to pure BTO. The enhanced piezoelectric performance observed in the Li-doped BTO nanoparticles can be attributed to the strategic substitution of Li atoms, which facilitated a more efficient transfer of charge charges at the interface. Overall, our study underscores the potential of piezocatalysis coupled with advanced materials like Li-doped BTO nanoparticles as a viable and promising solution for wastewater treatment, offering both efficiency and environmental sustainability.

Multi-Interface Engineering of MXenes for Self-Powered Wearable Devices.

Self-powered wearable devices with integrated energy supply module and sensitive sensors have significantly blossomed for continuous monitoring of human activity and the surrounding environment in healthcare sectors. The emerging of MXene-based materials has brought research upsurge in the fields of energy and electronics, owing to their excellent electrochemical performance, large surface area, superior mechanical performance, and tunable interfacial properties, where their performance can be further boosted via multi-interface engineering. Herein, a comprehensive review of recent progress in MXenes for self-powered wearable devices is discussed from the aspects of multi-interface engineering. The fundamental properties of MXenes including electronic, mechanical, optical, and thermal characteristics are discussed in detail. Different from previous review works on MXenes, multi-interface engineering of MXenes from termination regulation to surface modification and their impact on the performance of materials and energy storage/conversion devices are summarized. Based on the interfacial manipulation strategies, potential applications of MXene-based self-powered wearable devices are outlined. Finally, proposals and perspectives are provided on the current challenges and future directions in MXene-based self-powered wearable devices.

Stabilizing High-Voltage Performance of Nickel-Rich Cathodes via Facile Solvothermally Synthesized Niobium-Doped Strontium Titanate.

Ni-rich layered ternary cathodes are promising candidates thanks to their low toxic Co-content and high energy density (∼800 Wh/kg). However, a critical challenge in developing Ni-rich cathodes is to improve cyclic stability, especially under high voltage (>4.3 V), which directly affects the performance and lifespan of the battery. In this study, niobium-doped strontium titanate (Nb-STO) is successfully synthesized via a facile solvothermal method and used as a surface modification layer onto the LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode. The results exhibited that the Nb-STO modification significantly improved the cycling stability of the cathode material even under high-voltage (4.5 V) operational conditions. In particular, the best sample in our work could provide a high discharge capacity of ∼190 mAh/g after 100 cycles under 1 C with capacity retention over 84% in the voltage range of 3.0-4.5 V, superior to the pristine NCM811 (∼61%) and pure STO modified STO-811-600 (∼76%) samples under the same conditions. The improved electrochemical performance and stability of NCM811 under high voltage should be attributed to not only preventing the dissolution of the transition metals, further reducing the electrolyte's degradation by the end of charge, but also alleviating the internal resistance growth from uncontrollable cathode-electrolyte interface (CEI) evolution. These findings suggest that the as-synthesized STO with an optimized Nb-doping ratio could be a promising candidate for stabilizing Ni-rich cathode materials to facilitate the widespread commercialization of Ni-rich cathodes in modern LIBs.

Results of a Pilot External Quality Assessment Scheme for Genetic Testing of Newborns with Spinal Muscular Atrophy.

BACKGROUND: This study aims to evaluate the ability of laboratories to perform spinal muscular atrophy (SMA) genetic testing in newborns based on dried blood spot (DBS) samples, and to provide reference data and advance preparation for establishing the pilot external quality assessment (EQA) scheme for SMA genetic testing of newborns in China. METHODS: The pilot EQA scheme contents and evaluation principles of this project were designed by National Center for Clinical Laboratories (NCCL), National Health Commission. Two surveys were carried out in 2022, and 5 batches of blood spots were submitted to the participating laboratory each time. All participating laboratories conducted testing upon receiving samples, and test results were submitted to NCCL within the specified date. RESULTS: The return rates were 75.0% (21/28) and 95.2% (20/21) in the first and second surveys, respectively. The total return rate of the two examinations was 83.7% (41/49). Nineteen laboratories (19/21, 90.5%) had a full score passing on the first survey, while in the second survey twenty laboratories (20/20, 100%) scored full. CONCLUSIONS: This pilot EQA survey provides a preliminary understanding of the capability of SMA genetic testing for newborns across laboratories in China. A few laboratories had technical or operational problems in testing. It is, therefore, of importance to strengthen laboratory management and to improve testing capacity for the establishment of a national EQA scheme for newborn SMA genetic testing.

Ultrastructure of the antennal sensilla of the praying mantis Creobroter nebulosa Zheng (Mantedea: Hymenopodidae).

The praying mantis Creobroter nebulosa Zheng (Mantedea: Hymenopodidae) is an insect that has medicinal and esthetical importance, and being a natural enemy for many insects, the species is used as a biological control agent. In this publication, we used scanning electron microscopy (SEM) to study the fine morphology of antennae of males and females of this species. The antennae of both sexes are filiform and consist of three parts: scape, pedicel, and flagellum (differing in the number of segments). Based on the external morphology and the sensilla distribution, the antennal flagellum is could be divided into five regions. Seven sensilla types and eleven subtypes of sensilla were observed: grooved peg sensillum (Sgp), Bohm bristles (Bb), basiconic sensillum (Sb), trichoid sensillum (StI, StII), campaniform sensillum (Sca), chaetic sensillum (ScI, ScII, ScIII), and coeloconic sensillum (ScoI, ScoII). In Mantodea, the ScoII is observed for the first time, and it is located on the tip of the flagellum. The external structure and distribution of these sensilla are compared to those of other insects and possible functions of the antennal sensilla are discussed. The males and females of the mantis could be distinguished by the length of antennae and number of Sgp. Males have antennae about 1.5 times longer and have significantly larger number of Sgp compared to females. The sexual difference in distribution of the Sgp suggests that this type of sensilla may play a role in sex-pheromones detection in mantis.

The rise of baobab trees in Madagascar.

The baobab trees (genus Adansonia) have attracted tremendous attention because of their striking shape and distinctive relationships with fauna1. These spectacular trees have also influenced human culture, inspiring innumerable arts, folklore and traditions. Here we sequenced genomes of all eight extant baobab species and argue that Madagascar should be considered the centre of origin for the extant lineages, a key issue in their evolutionary history2,3. Integrated genomic and ecological analyses revealed the reticulate evolution of baobabs, which eventually led to the species diversity seen today. Past population dynamics of Malagasy baobabs may have been influenced by both interspecific competition and the geological history of the island, especially changes in local sea levels. We propose that further attention should be paid to the conservation status of Malagasy baobabs, especially of Adansonia suarezensis and Adansonia grandidieri, and that intensive monitoring of populations of Adansonia za is required, given its propensity for negatively impacting the critically endangered Adansonia perrieri.

Dual-responsive nanocarriers for efficient cytosolic protein delivery and CRISPR-Cas9 gene therapy of inflammatory skin disorders.

Developing protein drugs that can target intracellular sites remains a challenge due to their inadequate membrane permeability. Efficient carriers for cytosolic protein delivery are required for protein-based drugs, cancer vaccines, and CRISPR-Cas9 gene therapies. Here, we report a screening process to identify highly efficient materials for cytosolic protein delivery from a library of dual-functionalized polymers bearing both boronate and lipoic acid moieties. Both ligands were found to be crucial for protein binding, endosomal escape, and intracellular protein release. Polymers with higher grafting ratios exhibit remarkable efficacies in cytosolic protein delivery including enzymes, monoclonal antibodies, and Cas9 ribonucleoprotein while preserving their activity. Optimal polymer successfully delivered Cas9 ribonucleoprotein targeting NLRP3 to disrupt NLRP3 inflammasomes in vivo and ameliorate inflammation in a mouse model of psoriasis. Our study presents a promising option for the discovery of highly efficient materials tailored for cytosolic delivery of specific proteins and complexes such as Cas9 ribonucleoprotein.