Isotope-Labeled Chemoselective Probes for Labeling, Separation, and Comprehensive Quantitative Analysis of Sub-Metabolome.

The significance of small molecule metabolites as biomarkers for disease diagnosis and prognosis is growing increasingly evident, necessitating the development of highly sensitive qualitative and quantitative methods. Herein, multi-chemoselective probes are synthesized and applied for profiling metabolites, including carboxyl, phosphate, hydroxyl, amino, thiol, and carbonyl compounds. This approach seamlessly integrates magnetic solid-phase materials, orthogonal cleavage sites, isotopic tags, and selective coupling sites, minimizes matrix interference, and enhances quantitative accuracy. Meanwhile, a homemade program, High-Resolution Isotope-Assisted Identification and Quantitative (HRIAIQuant) is developed to process the data, which adeptly filters through 33,874 ion pairs present in human serum, leading to the identification of 701 known metabolites and a remarkable 1,062 potential novel ones. This method is successfully applied to analyze metabolites in multiple brain regions of SAMP8 and SAMR1 models, offering a novel tool for Alzheimer's disease research.

Ether-Based Gel Polymer Electrolyte for High-Voltage Potassium Ion Batteries.

Low-concentration ether electrolytes cannot efficiently achieve oxidation resistance and excellent interface behavior, resulting in severe electrolyte decomposition at a high voltage and ineffective electrode-electrolyte interphase. Herein, we utilize sandwich structure-like gel polymer electrolyte (GPE) to enhance the high voltage stability of potassium-ion batteries (PIBs). The GPE contact layer facilitates stable electrode-electrolyte interphase formation, and the GPE transport layer maintains good ionic transport, which enabled GPE to exhibit a wide electrochemical window and excellent electrochemical performance. In addition, Al corrosion under a high voltage is suppressed through the restriction of solvent molecules. Consequently, when using the designed GPE (based on 1 m), the K||graphite cell exhibits excellent cycling stability of 450 cycles with a capacity retention of 91%, and the K||FeFe-Prussian blue cell (2-4.2 V) delivers a high average Coulombic efficiency of 99.9% over 2200 cycles at 100 mA g-1. This study provides a promising path in the application of ether-based electrolytes in high-voltage and long-lasting PIBs.

AB048. Evidence of effectiveness of neoadjuvant camrelizumab and apatinib in patients with recurrent high-grade gliomas.

BACKGROUND: Recurrent high-grade glioma (HGG) is a challenge with limited treatment options and a poor prognosis. We conducted an open-label phase II study: neoadjuvant camrelizumab and apatinib in patients with recurrent high-grade gliomas (NCT04588987), and interim analysis showed very promising results. We are further searching for evidence of the effectiveness of this strategy. METHODS: Patients with recurrent HGG received neoadjuvant treatment with camrelizumab (intravenous injection 200 mg on day 1) and apatinib (oral 250 mg per day on days 1-7), and 14 days later received surgery for recurrent tumor resection. Sequential therapy began 2 weeks after surgery with the biweekly camrelizumab (200 mg) and 4 weeks after surgery with the daily apatinib (250 mg) until investigator assessed progressive disease or unable to tolerate toxicity. The primary endpoint was overall survival (OS). When patients suspected progress during per-protocol treatment, re-surgery for resection of lesion was done, and the tissue was further examined. RESULTS: Between October 9, 2020, and March 30, 2024, 24 patients were enrolled [19 glioblastomas, one World Health Organization (WHO) grade 4 diffuse astrocytoma, three anaplastic astrocytoma, and one anaplastic oligodendroglioma]. Nineteen patients with interim analysis data, and showed the median progression-free survival (PFS) was 4.8 months [95% confidence interval (CI): 4.4-5.2], the median OS was 12.9 months (95% CI: 9.3-16.4) respectively, with a median follow-up time of 17.5 months (95% CI: 9.0-26.1). There were two patients who suspected progress and received second surgery. One patient showed real tumor progression with active tumor cells. While another patient the histology revealed mainly necrosis with inflammatory cells. Five patients initially showed increased enhancement on magnetic resonance imaging (MRI) but without increased symptoms, and showed continuous improvement when receiving further treatment. CONCLUSIONS: This immuno-target combination neoadjuvant therapy in recurrent HGG demonstrated encouraging efficacy and revealed some evidence of efficacy, and worth to further investigate.

Guiding uniform Zn deposition with a multifunctional additive for highly utilized Zn anodes.

The practical applications of aqueous zinc-ion batteries (AZIBs) have been restricted by the fast growth of Zn dendrites and severe side reactions at the Zn/electrolyte interface. Herein, a multifunctional additive, L-leucine (Leu), is incorporated into a mild acidic electrolyte to stabilize the Zn anode. The Leu molecule, featuring both carboxyl and amino groups, exhibits strong interactions with Zn2+, which can reshape the solvation structure of Zn2+ and facilitate the uniform electrodeposition of Zn. Simultaneously, the Leu molecule exhibits preferential adsorption onto the Zn surface, effectively isolating it from direct contact with water, thus suppressing unwanted side reactions. Consequently, the Zn∥Cu asymmetric cell exhibits a high and stable coulombic efficiency of 99.5% at a current density of 5 mA cm-2 for 1100 h. Importantly, the capacity retention of the Zn∥NH4V4O10 full cell based on the Leu electrolyte reaches 80% after 1200 cycles at a current density of 2 A g-1. The successful application of the low-cost Leu effectively enhances the cycling stability of the AZIBs and accelerates their applications.

Oreonectes yuedongensis (Cypriniformes, Nemacheilidae), a new freshwater fish species from the Lianhua Mountains in eastern Guangdong, China.

In this work, we describe a new species of the genus Oreonectes, Oreonectes yuedongensis sp. nov., collected from the Lianhua Mountains in eastern Guangdong, China. Phylogenetic trees constructed based on the mitochondrial cytochrome b (Cyt b) gene showed that this new species represents an independent evolutionary lineage, with uncorrected genetic distances (Kimura 2-parameter model) from congeners ranging from 5.1% to 8.3%. In addition, nuclear DNA analysis indicated O. yuedongensis as an independent lineage separate from its closely related species. Morphologically, the new species can be distinguished from other six species in the genus Oreonectes by a combination of serial characters. The description of this new species suggests that it is necessary to reassess the biodiversity of Oreonectes platycephalus as a complex, especially in the middle reaches of the Pearl River near the border between Guangdong and Guangxi. Morphological and genetic evidence supports O. yenlingi as a synonym of O. platycephalus.

SARS-CoV-2 N protein-induced Dicer, XPO5, SRSF3, and hnRNPA3 downregulation causes pneumonia.

Though RNAi and RNA-splicing machineries are involved in regulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, their precise roles in coronavirus disease 2019 (COVID-19) pathogenesis remain unclear. Herein, we show that decreased RNAi component (Dicer and XPO5) and splicing factor (SRSF3 and hnRNPA3) expression correlate with increased COVID-19 severity. SARS-CoV-2 N protein induces the autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, inhibiting miRNA biogenesis and RNA splicing and triggering DNA damage, proteotoxic stress, and pneumonia. Dicer, XPO5, SRSF3, and hnRNPA3 knockdown increases, while their overexpression decreases, N protein-induced pneumonia's severity. Older mice show lower expression of Dicer, XPO5, SRSF3, and hnRNPA3 in their lung tissues and exhibit more severe N protein-induced pneumonia than younger mice. PJ34, a poly(ADP-ribose) polymerase inhibitor, or anastrozole, an aromatase inhibitor, ameliorates N protein- or SARS-CoV-2-induced pneumonia by restoring Dicer, XPO5, SRSF3, and hnRNPA3 expression. These findings will aid in developing improved treatments for SARS-CoV-2-associated pneumonia.

Prognosis in Patients with ST-Segment Elevation Myocardial Infarction Reperfused by PHDP: 1-Year MACEs Follow-Up.

This study explored 1-year follow-up of Parmaco-invasive strategy with half-dose recombinant human prourokinase (PHDP) in patients with acute ST-segment elevation myocardial infarction (STEMI). The follow-up endpoints were major adverse cardiovascular events (MACEs) occurring within 30 days and 1 year, as well as postoperative bleeding events. The study ultimately included 150 subjects, with 75 in the primary percutaneous coronary intervention (PPCI) group and 75 in the PHDP group. This study found that the PHDP group had a shorter FMC-reperfusion time (42.00 min vs 96.00 min, P < 0.001). During PCI, the PHDP group had a lower percutaneous transluminal coronary angioplasty (PTCA) (P = 0.021), intropin (P = 0.002) and tirofiban (P < 0.001) use. And the incidence of intraoperative arrhythmia, malignant arrhythmia, and slow flow/no-reflow was lower in the PHDP group (P < 0.001). At the 30-day follow-up, there was a significantly higher proportion of patients in the PPCI group who were readmitted due to unstable angina (P = 0.037). After 1 year of follow-up, there was no statistically significant difference in MACEs between the two groups (P = 0.500). The incidence of postoperative major bleeding, intracranial bleeding, and minor bleeding did not differ between the PHDP and PPCI groups (P > 0.05). The PHDP facilitates early treatment of infarct-related vessels, shortens FMC-reperfusion time, and does not increase the risk of MACEs.

Selection of Negative Charged Acidic Polar Additives to Regulate Electric Double Layer for Stable Zinc Ion Battery.

Zinc-ion batteries are promising for large-scale electrochemical energy storage systems, which still suffer from interfacial issues, e.g., hydrogen evolution side reaction (HER), self-corrosion, and uncontrollable dendritic Zn electrodeposition. Although the regulation of electric double layer (EDL) has been verified for interfacial issues, the principle to select the additive as the regulator is still misted. Here, several typical amino acids with different characteristics were examined to reveal the interfacial behaviors in regulated EDL on the Zn anode. Negative charged acidic polarity (NCAP) has been unveiled as the guideline for selecting additive to reconstruct EDL with an inner zincophilic H2O-poor layer and to replace H2O molecules of hydrated Zn2+ with NCAP glutamate. Taking the synergistic effects of EDL regulation, the uncontrollable interface is significantly stabilized from the suppressed HER and anti-self-corrosion with uniform electrodeposition. Consequently, by adding NCAP glutamate, a high average Coulombic efficiency of 99.83% of Zn metal is achieved in Zn|Cu asymmetrical cell for over 2000 cycles, and NH4V4O10|Zn full cell exhibits a high-capacity retention of 82.1% after 3000 cycles at 2 A g-1. Recapitulating, the NCAP principle posted here can quicken the design of trailblazing electrolyte additives for aqueous Zn-based electrochemical energy storage systems.

Two novel compounds inhibit Flavivirus infection in vitro and in vivo by targeting lipid metabolism.

Flavivirus infection capitalizes on cellular lipid metabolism to remodel the cellular intima, creating a specialized lipid environment conducive to viral replication, assembly, and release. The Japanese encephalitis virus (JEV), a member of the Flavivirus genus, is responsible for significant morbidity and mortality in both humans and animals. Currently, there are no effective antiviral drugs available to combat JEV infection. In this study, we embarked on a quest to identify anti-JEV compounds within a lipid compound library. Our research led to the discovery of two novel compounds, isobavachalcone (IBC) and corosolic acid (CA), which exhibit dose-dependent inhibition of JEV proliferation. Time-of-addition assays indicated that IBC and CA predominantly target the late stage of the viral replication cycle. Mechanistically, JEV nonstructural proteins 1 and 2A (NS1 and NS2A) impede 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activation by obstructing the liver kinase B1 (LKB1)-AMPK interaction, resulting in decreased p-AMPK expression and a consequent upsurge in lipid synthesis. In contrast, IBC and CA may stimulate AMPK by binding to its active allosteric site, thereby inhibiting lipid synthesis essential for JEV replication and ultimately curtailing viral infection. Most importantly, in vivo experiments demonstrated that IBC and CA protected mice from JEV-induced mortality, significantly reducing viral loads in the brain and mitigating histopathological alterations. Overall, IBC and CA demonstrate significant potential as effective anti-JEV agents by precisely targeting AMPK-associated signaling pathways. These findings open new therapeutic avenues for addressing infections caused by Flaviviruses. IMPORTANCE: This study is the inaugural utilization of a lipid compound library in antiviral drug screening. Two lipid compounds, isobavachalcone (IBC) and corosolic acid (CA), emerged from the screening, exhibiting substantial inhibitory effects on the Japanese encephalitis virus (JEV) proliferation in vitro. In vivo experiments underscored their efficacy, with IBC and CA reducing viral loads in the brain and mitigating JEV-induced histopathological changes, effectively shielding mice from fatal JEV infection. Intriguingly, IBC and CA may activate 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) by binding to its active site, curtailing the synthesis of lipid substances, and thus suppressing JEV proliferation. This indicates AMPK as a potential antiviral target. Remarkably, IBC and CA demonstrated suppression of multiple viruses, including Flaviviruses (JEV and Zika virus), porcine herpesvirus (pseudorabies virus), and coronaviruses (porcine deltacoronavirus and porcine epidemic diarrhea virus), suggesting their potential as broad-spectrum antiviral agents. These findings shed new light on the potential applications of these compounds in antiviral research.

Nrf2 Signaling Pathway: Focus on Oxidative Stress in Spinal Cord Injury.

Spinal cord injury (SCI) is a serious, disabling injury to the central nervous system that can lead to motor, sensory, and autonomic dysfunction below the injury plane. SCI can be divided into primary injury and secondary injury according to its pathophysiological process. Primary injury is irreversible in most cases, while secondary injury is a dynamic regulatory process. Secondary injury involves a series of pathological events, such as ischemia, oxidative stress, inflammatory events, apoptotic pathways, and motor dysfunction. Among them, oxidative stress is an important pathological event of secondary injury. Oxidative stress causes a series of destructive events such as lipid peroxidation, DNA damage, inflammation, and cell death, which further worsens the microenvironment of the injured site and leads to neurological dysfunction. The nuclear factor erythrocyte 2-associated factor 2 (Nrf2) is considered to be a key pathway of antioxidative stress and is closely related to the pathological process of SCI. Activation of this pathway can effectively inhibit the oxidative stress process and promote the recovery of nerve function after SCI. Therefore, the Nrf2 pathway may be a potential therapeutic target for SCI. This review deeply analyzed the generation of oxidative stress in SCI, the role and mechanism of Nrf2 as the main regulator of antioxidant stress in SCI, and the influence of cross-talk between Nrf2 and related pathways that may be involved in the pathological regulation of SCI on oxidative stress, and summarized the drugs and other treatment methods based on Nrf2 pathway regulation. The objective of this paper is to provide evidence for the role of Nrf2 activation in SCI and to highlight the important role of Nrf2 in alleviating SCI by elucidating the mechanism, so as to provide a theoretical basis for targeting Nrf2 pathway as a therapy for SCI.

An ionically cross-linked composite hydrogel electrolyte based on natural biomacromolecules for sustainable zinc-ion batteries.

Zinc-ion batteries (ZIBs) are regarded as promising power sources for flexible and biocompatible devices due to their good sustainability and high intrinsic safety. However, their applications have been hindered by the issues of uncontrolled Zn dendrite growth and severe water-induced side reactions in conventional liquid electrolytes. Herein, an ionically cross-linked composite hydrogel electrolyte based on natural biomacromolecules, including iota-carrageenan and sodium alginate, is designed to promote highly efficient and reversible Zn plating/stripping. The abundant functional groups of macromolecules effectively suppress the reactivity of water molecules and facilitate uniform Zn deposition. Moreover, the composite hydrogel electrolyte exhibits a high ionic conductivity of 5.89 × 10-2 S cm-1 and a Zn2+ transference number of 0.58. Consequently, the Zn‖Zn symmetric cell with the composite hydrogel electrolyte shows a stable cycle life of more than 500 h. Meanwhile, the Zn‖NH4V4O10 coin cell with the composite hydrogel electrolyte retains a high specific capacity of approximately 200 mA h g-1 after 600 cycles at 2 A g-1. The Zn‖NVO pouch cell based on the composite hydrogel electrolyte also shows a high specific capacity of 246.1 mA h g-1 at 0.5 A g-1 and retains 70.7% of its initial capacity after 150 cycles. The pouch cell performs well at different bending angles and exhibits a capacity retention rate of 98% after returning to its initial state from 180° folding. This work aims to construct high-performance hydrogel electrolytes using low-cost natural materials, which may provide a solution for the application of ZIBs in flexible biocompatible devices.

The Conservation Implications of the Gut Microbiome for Protecting the Critically Endangered Gray Snub-Nosed Monkey (Rhinopithecus brelichi).

The gut microbiota plays a crucial role in regulating energy metabolism, facilitating nutrient absorption, and supporting immune function, thereby assisting the host in adapting to seasonal dietary changes. Here, we compare the gut microbiome composition of wild gray snub-nosed monkeys during winter (from October to December) and spring (from January to March) to understand differences in seasonal nutrient intake patterns. Snub-nosed monkeys are foregut fermenters and consume difficult-to-digest carbohydrates and lichen. To examine the digestive adaptations of gray snub-nosed monkeys, we collected 14 fresh fecal samples for DNA analysis during the winter and spring. Based on 16S rRNA sequencing, metagenomic sequencing, and functional metagenomic analyses, we identified that Firmicutes, Actinobacteria, Verrucomicrobia, and Bacteroidetes constitute a keystone bacterial group in the gut microbiota during winter and spring and are responsible for degrading cellulose. Moreover, the transition in dietary composition from winter to spring was accompanied by changes in gut microbiota composition, demonstrating adaptive responses to varying food sources and availability. In winter, the bacterial species of the genera Streptococcus were found in higher abundance. At the functional level, these bacteria are involved in fructose and mannose metabolism and galactose metabolism c-related pathways, which facilitate the breakdown of glycogen, starch, and fiber found in fruits, seeds, and mature leaves. During spring, there was an increased abundance of bacteria species from the Prevotella and Lactobacillus genera, which aid the digestion of protein-rich buds. Combined, these findings reveal how the gut microbiota adjusts to fluctuations in energy balance and nutrient intake across different seasons in this critically endangered species. Moreover, we also identified Pseudomonas in two samples; the presence of potential pathogens within the gut could pose a risk to other troop members. Our findings highlight the necessity of a conservation plan that focuses on protecting vegetation and implementing measures to prevent disease transmission for this critically endangered species.

Insula-medial prefrontal cortex functional connectivity modulated by transcutaneous auricular vagus nerve stimulation: An fMRI study.

Transcutaneous auricular vagus nerve stimulation (taVNS) is an emerging neuro modulation technology that has been reported to be beneficial in the treatment of diseases by several studies, but its exact mechanism of action is still unclear. It has been demonstrated that ta VNS can influence interoceptive signals. Notably, the processing of interoceptive signals is directly related to many diseases, such as depression, anxiety, and insomnia. The insula and the medial prefrontal cortex (MPFC) communicate during the bottom-up transmission of taVNS-induced signals, and both play a role in interoceptive signal processing. By focusing on the insula and MPFC, our research pioneers detail the potential interactions between interoceptive signal processing and the neuromodulation effects of taVNS, providing novel insights in to the neurobiological mechanisms of taVNS. Two functional connectivity (FC) analyses (region of interest-based and seed-based) were used in this study. We observed that negative connectivity between the insula and the MPFC was significantly weakened following taVNS, while there were no statistical changes in the sham group. Our findings elucidate potential mechanisms linking vagal activity with intrinsic FC among specific brain regions and networks. Specifically, our results indicate that taVNS may enhance the ability to flexibly balance interoceptive awareness and cognitive experiences by modulating the FC between the insula and MPFC. The modulation effects may impact body-brain interactions, suggesting the mechanism of taVNS in therapeutic applications.

Predicting the potential distribution change of the endangered Francois' langur (Trachypithecus francoisi) across its entire range in China under climate change.

The Francois' langur (Trachypithecus francoisi) is a rare primate species indicated as endangered and distributed in karst areas in northern Vietnam and southwestern China. However, research limited to specific nature reserves or sites has hampered holistic conservation management. A comprehensive map of the potential distribution for the Francois' langur is essential to advance conservation efforts and ensure coordinated management across regions. Here, we used 82 occurrence records of Francois' langur surveyed in Guangxi, Guizhou, and Chongqing from 2017 to 2020, along with 12 environmental variables, to build the potential habitat model under current and future climate (2030, 2050, 2070, and 2090s) using maximum entropy models (MaxEnt). Our results indicated that (1) precipitation- and temperature-associated bioclimatic variables contributed the most to the distribution of Francois' langur. Vegetation, water sources, and anthropogenic variables also affected its distribution; (2) a total of 144,207.44 km2 of potential suitable habitat across the entire range in China was estimated by the current model. Moderate- and high-suitability habitats accounted for only 23.76% (34,265.96 km2) of the predicted suitable habitat and were mainly distributed in southwest Guangxi, east of Chongqing, and the border between Guizhou and Chongqing; (3) the suitable habitats of Francois' langur will contract considerably under future climate change, and the habitat centroid will move in the southeast direction with a shifting distance of approximately 2.84 km/year from current to 2100. The habitat prediction of Francois' langur and the main drivers proposed in this study could provide essential insights for the future conservation of this endangered species. The existing distribution areas should be monitored and protected, but conservation beyond existing habitats should also be a focus of effort, especially in future expansion areas. This would ensure effective and timely protection under climate change and anthropogenic pressures.

Spontaneous grain refinement effect of rare earth zinc alloy anodes enables stable zinc batteries.

Irreversible interfacial reactions at the anodes pose a significant challenge to the long-term stability and lifespan of zinc (Zn) metal batteries, impeding their practical application as energy storage devices. The plating and stripping behavior of Zn ions on polycrystalline surfaces is inherently influenced by the microscopic structure of Zn anodes, a comprehensive understanding of which is crucial but often overlooked. Herein, commercial Zn foils were remodeled through the incorporation of cerium (Ce) elements via the 'pinning effect' during the electrodeposition process. By leveraging the electron-donating effect of Ce atoms segregated at grain boundaries (GBs), the electronic configuration of Zn is restructured to increase active sites for Zn nucleation. This facilitates continuous nucleation throughout the growth stage, leading to a high-rate instantaneous-progressive composite nucleation model that achieves a spatially uniform distribution of Zn nuclei and induces spontaneous grain refinement. Moreover, the incorporation of Ce elements elevates the site energy of GBs, mitigating detrimental parasitic reactions by enhancing the GB stability. Consequently, the remodeled ZnCe electrode exhibits highly reversible Zn plating/stripping with an accumulated capacity of up to 4.0 Ah cm-2 in a Zn symmetric cell over 4000 h without short-circuit behavior. Notably, a ∼0.4 Ah Zn||NH4V4O10 pouch cell runs over 110 cycles with 83% capacity retention with the high-areal-loading cathode (≈20 mg cm-2). This refining-grains strategy offers new insights into designing dendrite-free metal anodes in rechargeable batteries.

Antireflective Superhydrophobic and Robust Coating Based on Chitin Nanofibers and Methylsilanized Silica for Outdoor Applications.

Antireflective coatings with superhydrophobicity have many outdoor applications, such as solar photovoltaic panels and windshields. In this study, we fabricated an omnidirectional antireflective and superhydrophobic coating with good mechanical robustness and environmental durability via the spin coating technique. The coating consisted of a layer of phytic acid (PA)/polyacrylamide (PAM)/calcium ions (Ca2+) (referred to as Binder), an antireflective layer composed of chitin nanofibers (ChNFs), and a hydrophobic layer composed of methylsilanized silica (referred to as Mosil). The transmittance of a glass slide with the Binder/ChNFs/Mosil coating had a 5.2% gain at a wavelength of 550 nm, and the antireflective coating showed a water contact angle as high as 160° and a water sliding angle of 8°. The mechanical robustness and environmental durability of the coating, including resistance to peeling, dynamic impact, chemical erosion, ultraviolet (UV) irradiation, and high temperature, were evaluated. The coating retained excellent antireflective capacity and self-cleaning performance in the harsh conditions. The increase in voltage per unit area of a solar panel with a Binder/ChNFs/Mosil coating reached 0.4 mV/cm2 compared to the solar panel exposed to sunlight with an intensity of 54.3 × 103 lx. This work not only demonstrates that ChNFs can be used as raw materials to fabricate antireflective superhydrophobic coatings for outdoor applications but also provides a feasible and efficient approach to do so.

Study of tree shrew biology and models: A booming and prosperous field for biomedical research.

The tree shrew ( Tupaia belangeri) has long been proposed as a suitable alternative to non-human primates (NHPs) in biomedical and laboratory research due to its close evolutionary relationship with primates. In recent years, significant advances have facilitated tree shrew studies, including the determination of the tree shrew genome, genetic manipulation using spermatogonial stem cells, viral vector-mediated gene delivery, and mapping of the tree shrew brain atlas. However, the limited availability of tree shrews globally remains a substantial challenge in the field. Additionally, determining the key questions best answered using tree shrews constitutes another difficulty. Tree shrew models have historically been used to study hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, myopia, and psychosocial stress-induced depression, with more recent studies focusing on developing animal models for infectious and neurodegenerative diseases. Despite these efforts, the impact of tree shrew models has not yet matched that of rodent or NHP models in biomedical research. This review summarizes the prominent advancements in tree shrew research and reflects on the key biological questions addressed using this model. We emphasize that intensive dedication and robust international collaboration are essential for achieving breakthroughs in tree shrew studies. The use of tree shrews as a unique resource is expected to gain considerable attention with the application of advanced techniques and the development of viable animal models, meeting the increasing demands of life science and biomedical research.

Interfacial Biomacromolecular Engineering Toward Stable Ah-Level Aqueous Zinc Batteries.

Interfacial instability within aqueous zinc batteries (AZBs) spurs technical obstacles including parasitic side reactions and dendrite failure to reach the practical application standards. Here, an interfacial engineering is showcased by employing a bio- derived zincophilic macromolecule as the electrolyte additive (0.037 wt%), which features a long-chain configuration with laterally distributed hydroxyl and sulfate anion groups, and has the propensity to remodel the electric double layer of Zn anodes. Tailored Zn2+-rich compact layer is the result of their adaptive adsorption that effectively homogenizes the interfacial concentration field, while enabling a hybrid nucleation and growth mode characterized as nuclei-rich and space-confined dense plating. Further resonated with curbed corrosion and by-products, a dendrite-free deposition morphology is achieved. Consequently, the macromolecule-modified zinc anode delivers over 1250 times of reversible plating/stripping at a practical area capacity of 5 mAh cm-2, as well as a high zinc utilization rate of 85%. The Zn//NH4V4O10 pouch cell with the maximum capacity of 1.02 Ah can be steadily operated at 71.4 mA g-1 (0.25 C) with 98.7% capacity retained after 50 cycles, which demonstrates the scale-up capability and highlights a "low input and high return" interfacial strategy toward practical AZBs.

A Cysteinyl-tRNA Synthetase Mutation Causes Novel Autosomal-Dominant Inheritance of a Parkinsonism/Spinocerebellar-Ataxia Complex.

This study aimed to identify possible pathogenic genes in a 90-member family with a rare combination of multiple neurodegenerative disease phenotypes, which has not been depicted by the known neurodegenerative disease. We performed physical and neurological examinations with International Rating Scales to assess signs of ataxia, Parkinsonism, and cognitive function, as well as brain magnetic resonance imaging scans with seven sequences. We searched for co-segregations of abnormal repeat-expansion loci, pathogenic variants in known spinocerebellar ataxia-related genes, and novel rare mutations via whole-genome sequencing and linkage analysis. A rare co-segregating missense mutation in the CARS gene was validated by Sanger sequencing and the aminoacylation activity of mutant CARS was measured by spectrophotometric assay. This pedigree presented novel late-onset core characteristics including cerebellar ataxia, Parkinsonism, and pyramidal signs in all nine affected members. Brain magnetic resonance imaging showed cerebellar/pons atrophy, pontine-midline linear hyperintensity, decreased rCBF in the bilateral basal ganglia and cerebellar dentate nucleus, and hypo-intensities of the cerebellar dentate nuclei, basal ganglia, mesencephalic red nuclei, and substantia nigra, all of which suggested neurodegeneration. Whole-genome sequencing identified a novel pathogenic heterozygous mutation (E795V) in the CARS gene, meanwhile, exhibited none of the known repeat-expansions or point mutations in pathogenic genes. Remarkably, this CARS mutation causes a 20% decrease in aminoacylation activity to charge tRNACys with L-cysteine in protein synthesis compared with that of the wild type. All family members carrying a heterozygous mutation CARS (E795V) had the same clinical manifestations and neuropathological changes of Parkinsonism and spinocerebellar-ataxia. These findings identify novel pathogenesis of Parkinsonism-spinocerebellar ataxia and provide insights into its genetic architecture.

A Bioinformatic Analysis of Gut Microbiota Related with Immune Cell Infiltration in Colorectal Cancer.

OBJECTIVE: The composition of microbiota which correlates with infiltrating immune cells and clinical signatures is not clarified in CRC. METHODS: We applied 4 kinds of bioinformatic tools GSVA (version: 1.42.0), ESTIMATE (version: 1.0.13), CIBERSORT (version: 2.0), and immune-related genes. RESULTS: We found that a total of 8 types of microbiotas appeared in the three immune correlation analyses. Among these microbiotas, significant enrichments in relative abundances associated with immune cell infiltration can be found for the dominant phyla Proteobacteria, Firmicutes, and Actinobacteria. Moreover, there existed correlations between some of the 8 microbiotas and clinical-related indicators. CONCLUSION: We identified some novel microbiotas involved in immune regulation in CRC.