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Abstract This study profiled global single cell-spatial-bulk transcriptome landscapes of hepatocellular carcinoma (HCC) ecosystem from six HCC cases and a non-carcinoma liver control donor. We discovered that intratumoral heterogeneity mainly derived from HCC cells diversity and pervaded the genome-transcriptome-proteome-metabolome network. HCC cells are the core driving force of taming tumor-associated macrophages (TAMs) with pro-tumorigenic phenotypes for favor its dominant growth. Remarkably, M1-types TAMs had been characterized by disturbance of metabolism, poor antigen-presentation and immune-killing abilities. Besides, we found simultaneous cirrhotic and HCC lesions in an individual patient shared common origin and displayed parallel clone evolution via driving disparate immune reprograms for better environmental adaptation. Moreover, endothelial cells exhibited phenotypically conserved but executed differential functions in a space-dependent manner. Further, the spatiotemporal traits of rapid recurrence niche genes were identified and validated by immunohistochemistry. Our data unravels the great significance of HCC cells in shaping vibrant tumor ecosystems corresponding to clinical scenarios.

Abstract Backgrounds To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined Lenvatinib plus Camrelizumab (TLC) in unresectable hepatocellular carcinoma (uHCC) with those of TACE alone . Methods A retrospective analysis was performed on 222 patients with uHCC who were treated between September 2013 and Jun 2023. One group received TACE + lenvatinib + camrelizumab (TLC) (n = 97) and another group received TACE alone (n = 151). Efficacy and safety were compared after propensity score matching between the TLC and TACE groups. Results After propensity matching, the TLC group had higher objective response rate (ORR) (88.6% vs. 28.6%, P

Single-crystalline layered oxide materials for lithium-ion batteries are featured by their excellent capacity retention over their polycrystalline counterparts, making them sought-after cathode candidates. Their capacity degradation, however, becomes more severe under high-voltage cycling, hindering many high-energy applications. It has long been speculated that the interplay among composition heterogeneity, lattice deformation, and redox stratification could be a driving force for the performance decay. The underlying mechanism, however, is not well-understood. In this study, we use X-ray microscopy to systematically examine single-crystalline NMC particles at the mesoscale. This technique allows us to capture detailed signals of diffraction, spectroscopy, and fluorescence, offering spatially resolved multimodal insights. Focusing on early high-voltage charging cycles, we uncover heterogeneities in valence states and lattice structures that are inherent rather than caused by electrochemical abuse. These heterogeneities are closely associated with compositional variations within individual particles. Our findings provide useful insights for refining material synthesis and processing for enhanced battery longevity and efficiency.

Background: The prognosis of hepatocellular carcinoma (HCC) is universally poor. Early diagnosis plays a pivotal role in determining the outcome of HCC. Methods: We employed a comparative proteomics approach to identify potential biomarkers and validated the application of retinol-binding protein 4 (RBP4) as a biomarker for HCC. RBP4 protein expression was examined in liver tissues from 80 HCC patients through immunohistochemical analysis. Serum RBP4 concentrations were measured by ELISA in a cohort comprising 290 HCC patients, matched 202 chronic hepatitis B patients and 269 healthy controls. Survival data were collected from HCC patients. The diagnostic and prognostic values of RBP4 were evaluated using receiver operating curve (ROC) analysis. Results: The validation results demonstrated a significant reduction in RBP4 levels in both liver tissues and serum samples from HCC patients. ROC analysis of the diagnostic value of RBP4 revealed an AUC of 0.879 (95 % CI: 0.854∼0.903) for HCC. When combined with AFP, the AUC increased to 0.919, with a sensitivity of 87.9 % and specificity of 80 %. Survival analysis revealed significantly reduced overall survival time in individuals with low-expression of RBP4 compared to those with high-expression. The joint prognostic model exhibited an AUC of 0.926 (95 % CI: 0.888∼0.964), which was significantly higher than that of AFP alone (AUC=0.809; P

Abstract To improve lithium-ion battery technology, it is essential to probe and comprehend the microscopic dynamic processes that occur in a real-world composite electrode under operating conditions. The primary and secondary particles are the structural building blocks of battery cathode electrodes. Their dynamic inconsistency has profound but not well-understood impacts. In this research, we combine operando coherent multi-crystal diffraction and optical microscopy to examine the chemical dynamics in local domains of layered oxide cathode. Our results not only pinpoint the asynchronicity of the lithium (de)intercalation at the sub-particle level, but also reveal sophisticated diffusion kinetics and reaction patterns, involving various localized processes, e.g., chemical onset, reaction front propagation, domains equilibration, particle deformation and motion. These observations shed new lights onto the activation and degradation mechanisms of state-of-the-art battery cathode materials.

Abstract Lampreys, one of two living lineages of jawless vertebrates, are always intriguing for their feeding behavior via the toothed suctorial disc and life cycle comprising the ammocoete, metamorphic, and adult stages. However, they left a meager fossil record, and their evolutionary history remains elusive. Here we report two superbly preserved large lampreys from the Middle-Late Jurassic Yanliao Biota of North China and update the interpretations of the evolution of the feeding apparatus, the life cycle, and the historic biogeography of the group. These fossil lampreys’ extensively toothed feeding apparatus differs radically from that of their Paleozoic kin but surprisingly resembles the Southern Hemisphere pouched lamprey, which foreshadows an ancestral flesh-eating habit for modern lampreys. Based on the revised petromyzontiform timetree, we argued that modern lampreys’ three-staged life cycle might not be established until the Jurassic when they evolved enhanced feeding structures, increased body size and encountered more penetrable host groups. Our study also places modern lampreys’ origin in the Southern Hemisphere of the Late Cretaceous, followed by an early Cenozoic anti-tropical disjunction in distribution, hence challenging the conventional wisdom of their biogeographical pattern arising from a post-Cretaceous origin in the Northern Hemisphere or the Pangean fragmentation in the Early Mesozoic.

Abstract The conventional weak acidic electrolyte for aqueous zinc-ion batteries breeds many challenges, such as undesirable side reactions, and inhomogeneous zinc dendrite growth, leading to low Coulombic efficiency, low specific capacity, and poor cycle stability. Here, an aqueous densified electrolyte, namely, a conventional aqueous electrolyte with addition of perovskite SrTiO3 powder, is developed to achieve high-performance aqueous zinc-ion batteries. The densified electrolyte demonstrates unique properties of reducing water molecule activity, improving Zn2+ transference number, and inducing homogeneous and preferential deposition of Zn (002). As a result, the densified electrolyte exhibits an ultra-long cycle stability over 1000 cycles in Zn/Ti half cells. In addition, the densified electrolyte enables Zn/MnO2 cells with a high specific capacity of 328.2 mAh g−1 at 1 A g−1 after 500 cycles under an extended voltage range. This work provides a simple strategy to induce dendrite-free deposition characteristics and high performance in high-voltage aqueous zinc-ion batteries.

Abstract Objective Depression and urinary incontinence (UI) are both troubling symptoms that severely impact quality of life. The aim of this study is to evaluate the association between UI (including UI types and severity) and depression among men. Population and methods The analyzed data was collected from the 2005–2018 National Health and Nutrition Examination Survey (NHANES) data. A total of 16,694 male participants aged ≥ 20 years with complete information about depression and UI were included in this study. Logistic regression was performed to calculate the odds ratio (OR) and 95% confidence interval (CI) to determine the association between depression and UI by adjusting for relevant covariables. Results The prevalence of depression was 10.91% among participants with UI. Urge UI was the main type of UI and accounts for 50.53% of all UI types. The adjusted ORs for the association between depression and UI were 2.69 (95%CI, 2.20–3.28). Compared with slight UI, the adjusted ORs were 2.28 (95% CI, 1.61–3.23) for moderate UI, 2.98 (95% CI, 1.54–5.74) for severe UI, and 3.85 (95% CI, 1.83–8.12) for very severe UI. Compared with no UI, the adjusted ORs were 4.46 (95% CI, 3.16–6.29) for mixed UI, 3.15 (95% CI, 2.06–4.82) for stress UI, and 2.43 (95% CI, 1.89–3.12) for urge UI. The subgroup analyses also showed similar correlation about depression and UI. Conclusion Among men, depression was positively associated with UI status, severity and types. For clinicians, it’s necessary to screen depression in patients with UI.

A typical solid-state quantum sensor can be developed based on negatively charged nitrogen-vacancy (NV−) centers in diamond. The electron spin state of NV− can be controlled and read at room temperature. Through optical detection magnetic resonance (ODMR) technology, temperature measurement can be achieved at the nanoscale. The key to ODMR technology is to apply microwave resonance to manipulate the electron spin state of the NV−. Therefore, the microwave field characteristics formed near the NV− have a crucial impact on the sensitivity of ODMR measurement. This article mainly focuses on the temperature situation in cellular applications and simulates the influence of structural parameters of double open loop resonant (DOLR) microwave antennas and broadband large-area (BLA) microwave antennas on the microwave field’s resonance frequency, quality factor Q, magnetic field strength, uniformity, etc. The parameters are optimized to have sufficient bandwidth, high signal-to-noise ratio, low power loss, and high magnetic field strength in the temperature range of 36 °C to 42.5 °C. Finally, the ODMR spectra are used for effect comparison, and the signal-to-noise ratio and Q values of the ODMR spectra are compared when using different antennas. We have provided an optimization method for the design of microwave antennas and it is concluded that the DOLR microwave antenna is more suitable for living cell temperature measurement in the future.

Abstract Background The intent of this research was to generate and investigate the D-dimer to lymphocyte ratio (DLR) capacity to forecast the risk and prognosis of colorectal cancer liver metastases (CRCLM). Methods From January 2010 to December 2019, 177 clinicopathologically confirmed colorectal cancer (CRC) patients (89 in the control group and 88 in the experimental group) were identified at the Affiliated Cancer Hospital of Guangxi Medical University. Multivariate Cox regression analysis was used to screen independent predictive diagnostic and prognostic factors of liver metastasis in CRC, and receiver operating characteristic (ROC) curves and Kaplan‒Meier (K‒M) curves were established to analyze the diagnostic and predictive prognostic efficacy of the DLR in the development of CRCLM. Results Patients with CRCLM had higher DLR levels and D-dimer levels in their blood, with statistically significant differences (p

Considering the high cost of cobalt, cobalt‐free lithium nickel oxide (LiNiO2), which has an extremely high theoretical specific capacity, has become attractive. However, its application is hampered by continuous irreversible phase changes, unstable interfaces, and particle pulverization. Herein, an ≈35 nm‐thick selenium (Se) coating is applied to modify LiNiO2 using a combination of solid‐phase mixing and low‐temperature sintering. After 300 cycles, the selenium‐coated LiNiO2 (Se–LNO) cathode exhibits unusually high capacity retention of 82.09% at a charge cutoff voltage of 4.3 V. Furthermore, the coating modification improves the rate performance of the cathode materials, which exhibit considerable specific capacities of 168.7 and 149.6 mAh g−1 at current densities of 2 and 5 C, respectively. The significantly enhanced electrochemical performance can be attributed to the ability of the Se coating to enhance the structural stability of the cathode materials by suppressing phase transitions, stabilizing the interface, enhancing the kinetic behavior of the electrode, and reducing particle pulverization. According to the findings of this study, manipulating the Se coating in cathodes may provide a viable path for lower‐cost and higher‐energy‐density Co‐free lithium‐ion batteries.

Spines are an important physical defense for many plant species. Here, the authors describe seven different spine morphologies from the Eocene of central Tibet associated with regional aridification and expansion of herbivorous mammals.

Sulfur cathode materials in lithium–sulfur chemistry suffer from poor electronic conductivity and shuttle of lithium polysulfides during charging and discharging. Serious shuttle effects and the sluggish redox reaction kinetics of polysulfides severely limit the development of lithium–sulfur batteries with high sulfur loading, impeding the practical process of lithium–sulfur batteries. Herein, a honeycomb73x02010;structured CoF2@C is introduced as a functional layer adhered to the separator, achieving rapid lithium‐ion transport, high catalytic activity, and suppressed shuttle effect simultaneously. As a result, the cell with CoF2‐modified separator presents satisfactory cycle stability with a capacity decay of 0.076% per cycle within 300 cycles at 1 C rate with the sulfur loading of 2.0 mg cm−2. A low‐capacity decay of 0.088% per cycle for 200 cycles at 0.2 C is also achieved with sulfur loading of 3.0 mg cm−2. In addition, a high‐capacity retention of 697.5 mA g−1 is achieved with sulfur loading of 4.0 mg cm−2 and the electrolyte volume/sulfur mass (E/S) ratio of 8 μL mg−1.

Electrochemical carbon dioxide reduction reaction (CO2RR) provides an attractive approach to carbon capture and utilization for the production high-value-added products. However, CO2RR still suffers from poor selectivity and low current density due to its sluggish kinetics and multitudinous reaction pathways. Single-atom catalysts (SACs) demonstrate outstanding activity, excellent selectivity, and remarkable atom utilization efficiency, which give impetus to the search for electrocatalytic processes aiming at high selectivity. There appears significant activity in the development of efficient SACs for CO2RR, while the density of the atomic sites remains a considerable barrier to be overcome. To construct high-metal-loading SACs, aggregation must be prevented, and thus novel strategies are required. The key to creating high-density atomically dispersed sites is designing enough anchoring sites, normally defects, to stabilize the highly mobile separated metal atoms. In this review, we summarized the advances in developing high-loading SACs through defect engineering, with a focus on the synthesis strategies to achieve high atomic site loading. Finally, the future opportunities and challenges for CO2RR in the area of high-loading single-atom electrocatalysts are also discussed.

BackgroundAlthough dexmedetomidine (DEX) is widely used during the perioperative period in patients with hepatocellular carcinoma (HCC), its clinical effects on liver function and postoperative inflammation are unclear. This study aimed to explore effects of DEX on postoperative liver function and inflammation in patients with HCC after hepatectomy.MethodsA retrospective cohort study with propensity score matching was performed. A total of 494 patients who underwent hepatectomy from June 2019 to July 2020 and fulfilled the eligibility criteria were included in this study. Baseline data, liver function indexes and inflammation-related biomarkers were collected and compared between the two groups. Survival analysis was conducted to investigate the effects of DEX on the overall survival (OS) of patients. Propensity score matching (PSM) was used to minimize bias between the two groups.ResultsThe study cohort comprised 189 patients in the DEX-free group and 305 patients in the DEX group. Patients in the DEX group had lower levels of alanine transaminase (ALT, P = 0.018) and lactate dehydrogenase (LDH, P = 0.046) and higher level of serum albumin (ALB, P < 0.001) than patients in the DEX-free group before discharge. A total of 107 pairs of patients were successfully matched by PSM. Results consistently suggested that ALT and LDH levels were significantly lower (P = 0.044 and P = 0.046, respectively) and ALB levels were significantly higher (P = 0.002) in the DEX group than in the DEX-free group in the early postoperative period. No significant differences of inflammation-related biomarkers were observed between two groups after PSM. Neither the Kaplan–Meier survival analysis nor the multiple Cox regression survival analysis identified DEX as a contributing factor that would affect the OS of patients after PSM.ConclusionDEX exerts protective effects on liver function while has little effects on inflammation-related biomarkers in the early postoperative period in patients undergoing hepatectomy due to HCC.

PurposeTo evaluate the outcomes and prognostic factors for patients using conversion therapy with lenvatinib combined with transcatheter arterial chemoembolization (TACE) plus programmed cell death protein-1 (PD-1) inhibitors (LTP) for initially unresectable hepatocellular carcinoma (iuHCC).MethodsData on 94 consecutive patients with iuHCC who received LTP conversion therapy from November 2019 to September 2022 were retrospectively analyzed. Early tumor response was reported when patients showed complete or partial response at the time of their first follow-up (4–6 weeks) after initial treatment, in accordance with mRECIST. The endpoints consisted of conversion surgery rate, overall survival (OS), and progression-free survival (PFS).ResultsEarly tumor response was found in 68 patients (72.3%) and not in the remaining 26 patients (27.7%) in the entire cohort. Early responders had a significantly higher conversion surgery rate than non-early responders (44.1% vs. 7.7%, p=0.001). Early tumor response was the only factor independently associated with successful conversion resection, as indicated by multivariate analysis (OR=10.296; 95% CI: 2.076–51.063; p=0.004). Survival analysis showed that early responders had longer PFS (15.4 vs. 7.8 months, p=0.005) and OS (23.1 vs. 12.5 months, p=0.004) than non-early responders. Early responders who underwent conversion surgery also had significantly longer median PFS and OS (not reached, not reached) than those who did not (11.2 months, p=0.004; 19.4 months, p

BackgroundAcute respiratory distress syndrome (ARDS) is a serious organ failure and postoperative complication. However, the incidence rate, early prediction and prevention of postoperative ARDS in patients undergoing hepatectomy remain unidentified.MethodsA total of 1,032 patients undergoing hepatectomy between 2019 and 2020, at the Eastern Hepatobiliary Surgery Hospital were included. Patients in 2019 and 2020 were used as the development and validation cohorts, respectively. The incidence rate of ARDS was assessed. A logistic regression model and a least absolute shrinkage and selection operator (LASSO) regression model were used for constructing ARDS prediction models.ResultsThe incidence of ARDS was 8.8% (43/490) in the development cohort and 5.7% (31/542) in the validation cohort. Operation time, postoperative aspartate aminotransferase (AST), and postoperative hemoglobin (Hb) were all critical predictors identified by the logistic regression model, with an area under the curve (AUC) of 0.804 in the development cohort and 0.752 in the validation cohort. Additionally, nine predictors were identified by the LASSO regression model, with an AUC of 0.848 in the development cohort and 0.786 in the validation cohort.ConclusionWe reported the incidence of ARDS in patients undergoing hepatectomy and developed two simple and practical prediction models for early predicting postoperative ARDS in patients undergoing hepatectomy. These tools may improve clinicians’ ability to early estimate the risk of postoperative ARDS and timely prevent its emergence.

Dysregulation of lipid metabolism and transport contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Here the authors identify GP73 as a TBC-domain Rab GTPase-activating protein that regulates very low-density lipoprotein export and promotes NAFLD development in mice.

ObjectiveTo compare overall survival (OS) and cancer-specific survival (CSS) in renal pelvic urothelial carcinoma (RPUC) patients treated with radical nephroureterectomy (NU) and inadvertent radical nephrectomy (RN).Patients and methodsIn this retrospective study, patients with RPUC who underwent NU or RN diagnosed between 2004 and 2017 were identified from the Surveillance, Epidemiology, and End Results database. To adjust the confounders, the propensity score-matched analysis was conducted. The Kaplan–Meier method and log-rank test were performed to explore the effect of different surgical methods on OS and CSS.ResultsA total of 2197 cases were finally included in this analysis, among which, 187 (8.5%) patients were treated with RN and 2010 (91.5%) patients were treated with NU. Before matching, the survival analysis revealed that the OS (HR: 1.444, 95%CI: 1.197, 1.741) and CSS (HR: 1.522, 95%CI: 1.211, 1.914) of patients who received RN were worse than that of patients who received NU (p = 0.0001 and p = 0.0003, respectively). After matching, the RN group had a worse OS (HR: 1.298, 95%CI: 1.002, 1.682) than the NU group (p = 0.048). No significant difference was observed in CSS between the RN and NU groups (p = 0.282). The hierarchical analysis showed that there was no significant difference observed in OS and CSS in patients with tumor size ≤4.2 cm (p = 0.884 and p = 0.496, respectively). In tumor size >4.2 cm, both OS (HR: 1.545, 95%CI: 1.225, 1.948) and CSS (HR: 1.607, 95%CI: 1.233, 2.095) of patients who received RN were worse than those of patients who received NU (p = 0.0002 and p = 0.0005).ConclusionRN could lead to worse oncological outcomes than NU in patients with renal pelvis urothelial carcinoma. Accurate diagnosis of renal pelvis urothelial carcinoma is extremely important.

Background: Hepatocellular carcinoma (HCC) is a highly heterogeneous disease with high morbidity and mortality, which accounts for the fourth most common cause of cancer-related deaths. Reports suggest that the neurotransmitter receptor-related genes (NRGs) may influence the tumor microenvironment and the prognosis of patients with HCC.Methods: The clinical information and RNA-seq data of patients with HCC were acquired from the ICGC-LIRI-JP dataset and the TCGA-LIHC dataset. Effects of 115 NRGs on the prognosis of HCC patients were analyzed in the ICGC-LIRI-JP dataset. The least absolute shrinkage and selection operator (LASSO) regression model was utilized to generate a risk score formula based on the critical NRGs. Next, the risk score effectiveness was validated both in the TCGA-LIHC dataset and in our clinical HCC samples. Based on the risk scores, patients with HCC were divided into two groups. Moreover, differentially expressed genes (DEGs) were screened. The gene ontology (GO) was used to analyze the functional enrichments of DEGs and to identify potential signaling pathways. To test the diagnostic effectiveness of our model, the receiver operator characteristic curve (ROC) analysis and nomogram were used. Finally, potential targeted drug prediction was performed based on DEGs of nine clinical HCC samples.Results: Nine NRGs were correlated significantly with the prognosis of patients with HCC, and eight NRGs were successfully included in the LASSO regression model. The Kaplan-Meier analysis of overall survival (OS) suggested that patients in the high-risk score group had worse prognosis; on the other hand, ROC analysis revealed a high prognostic value of the risk score in HCC. Several critical signaling pathways, such as lipid metabolism, organic acid metabolism, cell migration, cell adhesion, and immune response, were enriched both in public datasets and clinical samples. Nomogram results also suggested that the risk scores correlated well with the patients’ prognosis. Potential targeted drugs prediction revealed that tubulin inhibitors might be the promising drugs for patients with HCC who have high risk scores based on the NRGs.Conclusion: We established a prognostic model based on critical NRGs. NRGs show a promising prognostic prediction value in HCC and are potential therapeutic targets for the disease treatment.

As a critical immune checkpoint molecule, PD-L1 is expressed at significantly higher levels in multiple neoplastic tissues compared to normal ones. PD-L1/PD-1 axis is a critical target for tumor immunotherapy, blocking the PD-L1/PD-1 axis is recognized and has achieved unprecedented success in clinical applications. However, the clinical efficacy of therapies targeting the PD-1/PD-L1 pathway remains limited, emphasizing the need for the mechanistic elucidation of PD-1/PD-L1 expression. In this study, we found that RNF125 interacted with PD-L1 and regulated PD-L1 protein expression. Mechanistically, RNF125 promoted K48-linked polyubiquitination of PD-L1 and mediated its degradation. Notably, MC-38 and H22 cell lines with RNF125 knockout, transplanted in C57BL/6 mice, exhibited a higher PD-L1 level and faster tumor growth than their parental cell lines. In contrast, overexpression of RNF125 in MC-38 and H22 cells had the opposite effect, resulting in lower PD-L1 levels and delayed tumor growth compared with parental cell lines. In addition, immunohistochemical analysis of MC-38 tumors with RNF125 overexpression showed significantly increased infiltration of CD4+, CD8+ T cells and macrophages. Consistent with these findings, analyses using The Cancer Genome Atlas (TCGA) public database revealed a positive correlation of RNF125 expression with CD4+, CD8+ T cell and macrophage tumor infiltration. Moreover, RNF125 expression was significantly downregulated in several human cancer tissues, and was negatively correlated with the clinical stage of these tumors, and patients with higher RNF125 expression had better clinical outcomes. Our findings identify a novel mechanism for regulating PD-L1 expression and may provide a new strategy to increase the efficacy of immunotherapy.

The Triassic has long been recognized as a time during which marine and terrestrial ecosystems modernized dramatically, and it seems to have been a two-step process. First, recovery from the Permian-Triassic mass extinction (PTME) was a time of extraordinary renewal and novelty, and these processes of change were enhanced, it seems, by the effects of the Carnian Pluvial Episode (CPE). After the CPE, in the oceans, not only did the carbonate factory begin to change towards its modern form, but also arguably the Mesozoic Marine Revolution (MMR) speeded up. When the MMR was proposed it was seen as a process that occurred in the Late Jurassic and Cretaceous, as modern crustaceans, gastropods, and fishes enhanced predator-prey arms races. New evidence from China and elsewhere suggests in fact the MMR was already underway in the Middle and Late Triassic, and so was coincident with Sepkoski’s classic idea that Paleozoic faunas were replaced by Modern marine faunas from the beginning of the Triassic. On land, ongoing competition between synapsids and archosauromorphs through the Triassic was marked by a posture shift from sprawling to erect, and a shift in physiology to warm-bloodedness, with insulating skin coverings of hair and feathers. Dinosaurs, for example, originated in the Early or Middle Triassic, but did not diversify until after the CPE. These arms races, the MMR in the sea, and the endothermy shift in tetrapods, were triggered by the PTME, and then enhanced by the CPE.

Abstract Solid‐state batteries have been considered as promising next‐generation energy storage devices for potentially higher energy density and better safety compared with commercial lithium‐ion batteries that are based on organic liquid electrolytes. However, in terms of indispensable solid‐state electrolytes, there are remaining issues to be solved before entering the market. Most solid‐state electrolytes are air‐sensitive, which causes a complex and expensive cell assembly and impressible interface. Therefore, the solid‐state electrolytes are expected to be atmosphere‐stable, which will undoubtedly bring significant benefits to solid‐state battery manufacturing. This review covers air‐stability‐related issues of different types of inorganic solid‐state electrolytes and the corresponding strategies. First, we provide an overview of solid‐state electrolytes and solid‐state batteries, including their history and advantages/disadvantages. Then, different types of solid‐state electrolytes are selected as examples to illustrate the unfavorable interactions in air and the corresponding adverse effects. Next, according to recent advances, we summarize the effective strategies of constructing different types of air‐stable inorganic solid‐state electrolytes. Finally, perspectives on designing accessible air‐stable solid‐state electrolytes are provided, aiming to achieve the assembly of high‐performance solid‐state batteries in the atmosphere.

Abstract Background Hypoxic preconditioning (HPC) may protect multiple organs from various injuries. We hypothesized that HPC would reduce lung injury in patients undergoing thoracoscopic lobectomy. Methods In a prospective randomized controlled trial, 70 patients undergoing elective thoracoscopic lobectomy were randomly allocated to the HPC group or the control group. Three cycles of 5-min hypoxia and 3-min ventilation applied to the nondependent lung served as the HPC intervention. The primary outcome was the PaO2/FiO2 ratio. Secondary outcomes included postoperative pulmonary complications, pulmonary function, and duration of hospital stay. Results HPC significantly increased the PaO2/FiO2 ratio compared with the control at 30 min after one-lung ventilation and 7 days after operation. Compared with the control, it also significantly improved postoperative pulmonary function and markedly reduced the postoperative hospital stay duration. No significant differences between groups were observed in the incidence of pulmonary complications or overall postoperative morbidity. Conclusions HPC improves postoperative oxygenation, enhances the recovery of pulmonary function, and reduces the duration of hospital stay in patients undergoing thoracoscopic lobectomy. Trial registration This study was registered in the Chinese Clinical Trial Registry (ChiCTR-IPR-17011249) on April 27, 2017.

A new ellimmichthyiform, Guiclupea superstes, gen. et sp. nov., from the Oligocene Ningming Formation of Ningming Basin, Guangxi Zhuang Autonomous Region, South China is described herein. With relatively large body size, parietals meeting at the midline, anterior ceratohyal with a beryciform foramen in the center, a complete predorsal scutes series of very high number and about equally-size scutes with radiating ridges on dorsal surface, first preural centrum unfused with first uroneural but fused with the parhypural, and first ural centrum of roughly the same size as the preural centrum, Guiclupea superstes cannot be assigned to the order Clupeiformes. The phylogenetic analyses using parsimony and Bayesian inference methods with Chanos/Elops as outgroup respectively suggests that the new form is closer to ellimmichthyiform genus Diplomystus than to any other fishes, although there are some discrepancies between the two criteria and different outgroups used. It shares with Diplomystus the high supraoccipital crest, pelvic-fin insertion in advance of dorsal fin origin, and the number of predorsal scutes more than 20. The new form represents the youngest ellimmichthyiform fish record in the world. Its discovery indicates that the members of the Ellimmichthyiformes had a wider distribution range and a longer evolutional history than previously known.

BackgroundCholestasis patients often suffer from pain desensitization, resulting in serious complications in perioperative period. This study was aim to investigate the mechanism of bilirubin in cholestasis mediating pain desensitization through 5-hydroxytryptamine 3A (5-HT3A) receptor activation in spinal dorsal horn (SDH).MethodsA cholestasis model was established by bile duct ligation (BDL) in rats. Pain thresholds of rats were measured after BDL or intrathecally injecting bilirubin in the presence or absence of agonist (mCPBG) and antagonists (ondansetron, bicuculline, or CGP55845). Expression of 5-HT3 receptors, and the affinity and binding mode of bilirubin to 5-HT3A receptor were determined. Effects of bilirubin on γ-aminobutyric acid (GABA) pathway and the interactions with 5-HT3A receptor were tested.ResultsBilirubin was elevated significantly in both serum and CSF in BDL rats, accompanied with the up-regulation of pain thresholds. Both of 5-HT3A receptor and GABAA receptor antagonists could reverse the increased pain threshold in BDL rats. Further, 5-HT3A and GABAA receptor expressions were increased in BDL rats or intervention with bilirubin. Molecular docking suggested that bilirubin entered the hydrophobic pocket pre-formed in 5-HT3A receptor with potential hydrogen bonding. Bilirubin also increased GABA concentrations in CSF and GABAergic spontaneous inhibitory postsynaptic current in spinal cord, and directly induced inward currents in HEK293 cells which were overexpressed 5-HT3A receptor by lentivirus.ConclusionIn conclusion, bilirubin induced pain desensitization in cholestasis by activating 5-HT3A receptor in spinal cord. The activation of 5-HT3A receptor might regulate pain threshold by acting on the GABA pathway.

Layered cathode oxides have been attractive for next-generation high-energy-density rechargeable batteries, only that they are approaching the bottleneck of limited specific capacities based on cation redox reactions. Recently, the utilization of anion redox reaction to participate in charge compensation is an important strategy to increase the upper limit of energy density, but it faces issues such as voltage hysteresis and structure decay. In this review, we discuss the anion redox chemistry and the problems faced by such materials. Subsequently, we reviewed the recent research progress from perspectives of transition metal layer design and stacking fault design, hoping to provide a guide for the design of layered oxide cathodes.

Summary: Recent reports have shown the critical role of the mitochondrial antiviral signaling (MAVS) protein in virus-induced apoptosis, but the involvement of MAVS in tumorigenesis is still poorly understood. Herein, we report that MAVS is a key regulator of p53 activation and is critical for protecting against tumorigenesis. We find that MAVS promotes p53-dependent cell death in response to DNA damage. MAVS interacts with p53 and mediates p53 mitochondrial recruitment under genotoxic stress. Mechanistically, MAVS inhibits p53 ubiquitination by blocking the formation of the p53-murine double-minute 2 (MDM2) complex, leading to the stabilization of p53. Notably, compared with their wild-type littermates, MAVS knockout mice display decreased resistance to azoxymethane (AOM) or AOM/dextran sulfate sodium salt (DSS)-induced colon cancer. MAVS expression is significantly downregulated in human colon cancer tissues. These results unveil roles for MAVS in DNA damage response and tumor suppression. : Zhang et al. show that MAVS interacts with p53 and regulates p53-dependent apoptosis, indicating roles for MAVS in tumor suppression and the DNA damage response. Keywords: MAVS, p53, ubiquitination, tumor suppression

Abstract Background Misregulation of the p53-mdm2 loop function is a major mechanism to promote hepatocellular carcinoma (HCC). RBM38, a member of the RNA recognition motif (RRM) family of RNA binding proteins (RBPs), plays a fundamental role in the posttranscriptional control of gene expression and regulatory functions in human tumors. A novel RBM38-p53-mdm2 autoregulatory feedback loop has been demonstrated. However, its mechanistic role in HCC remains unclear. Methods In the present study, we investigated the role and molecular mechanism of misregulation in the p53-mdm2 loop function by RBM38 in HCC. First we investigated the correlation of RBM38 activity and p53-mdm2 loop function in liver cancer cells and HCC tissues by western blot and quantitative RT-PCR. We then conducted functional assays to investigate the molecular roles of RBM38 in inhibiting liver cancer cells aggressiveness in vitro and suppressing tumorigenicity in vivo. Results We observed RBM38 protein expression was commonly silenced coupled with increased mdm2 and decreased wild type (wt) p53 in liver cancer cells and HCC tissues compared to the corresponding normal liver cells and adjacent liver tissues. RBM38 mRNA level was significantly lower in HCC than adjacent liver tissues, whereas mdm2 and wtp53 mRNA levels were similar between HCC and adjacent liver tissues. This implied that deactivation of RBM38 could disrupt the p53-mdm2 loop and promote HCC, even though p53 and mdm2 transcript amounts were stable. Then, we generated stable liver cancer cell lines with overexpressed RBM38 (RBM38-OE) and found that up-regulation of RBM38 could inhibit mdm2 and restore wtp53 expression. Luciferase assay shown that RBM38 destabilized the mdm2 transcript through binding to multiple AU-/U-rich elements in mdm2 3’-UTR. Furthermore, functional assays showed that ectopic expression of RBM38 could induce liver cancer cell apoptosis and senescence, inhibit proliferation and colony growth, and suppress migration and invasion in vitro. Lastly, RBM38 could suppress HCC tumorigenicity in vivo. Conclusion Our findings suggested that RBM38 may be a core contributor in stabilizing the p53-mdm2 loop function to prevent HCC, and a potential novel target to provide a therapeutic strategy for HCC by inhibiting mdm2 and rescuing p53 from inactivation.

Abstract Understanding the Tibetan Plateau’s palaeogeography and palaeoenvironment is critical for reconstructing Asia’s climatic history; however, aspects of the plateau’s uplift history remain unclear. Here, we report a fossil biota that sheds new light on these issues. It comprises a fossil climbing perch (Anabantidae) and a diverse subtropical fossil flora from the Chattian (late Oligocene) of central Tibet. The fish, Eoanabas thibetana gen. et sp. nov., is inferred to be closely related to extant climbing perches from tropical lowlands in south Asia and sub-Saharan Africa. It has osteological correlates of a labyrinth organ, which in extant climbing perches gives them the ability to breathe air to survive warm, oxygen-poor stagnant waters or overland excursion under moist condition. This indicates that Eoanabas likewise lived in a warm and humid environment as suggested by the co-existing plant assemblage including palms and golden rain trees among others. As a palaeoaltimeter, this fossil biota suggests an elevation of ca. 1,000 m. These inferences conflict with conclusions of a high and dry Tibet claimed by some recent and influential palaeoaltimetry studies. Our discovery prompts critical re-evaluation of prevailing uplift models of the plateau and their temporal relationships with the Cenozoic climatic changes.

Lithium-based batteries employing silicon anodes and sulfur cathodes are promising for combining low cost and high capacity, but have been limited in terms of cycling stability. Here authors present cycling and characterization data supporting beneficial synergies between a selenium disulfide cathode and a silicon anode.

The labyrinth fishes (Anabantoidei/Anabantiformes) have an African-Asian disjunctive distribution; however, their biogeographical history remains elusive due to the scarcity of their fossil records, especially for the Anabantidae itself, the only anabantoid family with a disjunctive biogeography. A time-calibrated anabantoid phylogeny incorporating both fossil and extant taxa and a likelihood dispersal extinction and cladogenesis (EDC) model in the software package of LAGRANGE were used to infer the ancestral areas of main lineages of the anabantoid fishes. The results suggest that" before "the split of the Asian and African anabantids is a recent event The split of the Asian-African anabantid is a recent event. The traditional drift vicariance hypothesis and the late Cretaceous or early Tertiary dispersal hypotheses are now called into question for the interpretation of the anabantid biogeographical pattern.

Polymer composites with high thermal conductivity have a great potential for applications in modern electronics due to their low cost, easy process, and stable physical and chemical properties. Nevertheless, most polymer composites commonly possess unsatisfactory thermal conductivity, primarily because of the high interfacial thermal resistance between inorganic fillers. Herein, we developed a novel method through silver functionalized graphene nanosheets (GNS) and multiwalled carbon nanotube (MWCNT) composites with excellent thermal properties to meet the requirements of thermal management. The effects of composites on interfacial structure and properties of the composites were identified, and the microstructures and properties of the composites were studied as a function of the volume fraction of fillers. An ultrahigh thermal conductivity of 12.3 W/mK for polymer matrix composites was obtained, which is an approximate enhancement of 69.1 times compared to the polyvinyl alcohol (PVA) matrix. Moreover, these composites showed more competitive thermal conductivities compared to untreated fillers/PVA composites applied to the desktop central processing unit, making these composites a high-performance alternative to be used for thermal management.

Although bone cancer pain is still not fully understood by scientists and clinicians alike, studies suggest that toll like receptor 4 (TLR4) plays an important role in the initiation and/or maintenance of pathological pain state in bone cancer pain. A promising treatment for bone cancer pain is the downregulation of TLR4 by RNA interference; however, naked siRNA (small interference RNA) is not effective in long-term treatments. In order to concoct a viable prolonged treatment for bone cancer pain, an inducible lentivirus LvOn-siTLR4 (tetracycline inducible lentivirus carrying siRNA targeting TLR4) was prepared and the antinociception effects were observed in bone cancer pain rats induced by Walker 256 cells injection in left leg. Results showed that LvOn-siTLR4 intrathecal injection with doxycycline (Dox) oral administration effectively reduced the nociception induced by Walker 256 cells while inhibiting the mRNA and protein expression of TLR4. Proinflammatory cytokines as TNF-α and IL-1β in spinal cord were also decreased. These findings suggest that TLR4 could be a target for bone cancer pain treatment and tetracycline inducible lentivirus LvOn-siTLR4 represents a new potential option for long-term treatment of bone cancer pain.

BACKGROUND: Reactive oxygen and nitrogen species are key molecules that mediate neuropathic pain. Although hydrogen is an established antioxidant, its effect on chronic pain has not been characterized. This study was to investigate the efficacy and mechanisms of hydrogen-rich normal saline induced analgesia. METHODOLOGY/PRINCIPAL FINDINGS: In a rat model of neuropathic pain induced by L5 spinal nerve ligation (L5 SNL), intrathecal injection of hydrogen-rich normal saline relieved L5 SNL-induced mechanical allodynia and thermal hyperalgesia. Importantly, repeated administration of hydrogen-rich normal saline did not lead to tolerance. Preemptive treatment with hydrogen-rich normal saline prevented development of neuropathic pain behavior. Immunofluorochrome analysis revealed that hydrogen-rich normal saline treatment significantly attenuated L5 SNL-induced increase of 8-hydroxyguanosine immunoreactive cells in the ipsilateral spinal dorsal horn. Western blot analysis of SDS/PAGE-fractionated tyrosine-nitrated proteins showed that L5 SNL led to increased expression of tyrosine-nitrated Mn-containing superoxide dismutase (MnSOD) in the spinal cord, and hydrogen-rich normal saline administration reversed the tyrosine-nitrated MnSOD overexpression. We also showed that the analgesic effect of hydrogen-rich normal saline was associated with decreased activation of astrocytes and microglia, attenuated expression of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the spinal cord. CONCLUSION/SIGNIFICANCE: Intrathecal injection of hydrogen-rich normal saline produced analgesic effect in neuropathic rat. Hydrogen-rich normal saline-induced analgesia in neuropathic rats is mediated by reducing the activation of spinal astrocytes and microglia, which is induced by overproduction of hydroxyl and peroxynitrite.

BackgroundEquipped with an effective predatory feeding mechanism enhanced by large and sharp teeth, pointed snout and elongate body, saurichthyiform fishes are considered common fish-eaters in the early Mesozoic aquatic ecosystems. Additionally, because of the similar body plan across species, saurichthyiforms are also regarded evolutionally conservative, with few morphological and ecological changes during their long history. However, their phylogenetic affinity remains unclear as to whether they are chondrostean, neopterygian or stem-actinopteran, and likewise the intrarelationships of the group have rarely been explored.Methodology/principal findingsHere we report a new saurichthyiform from the Middle Triassic of Guizhou, China, based on the well-preserved specimens including a 3-D braincase. The new taxon, Yelangichthys macrocephalus gen. et sp. nov., is unique among saurichthyiforms in having a peculiar neurocranium with a broad orbital tectum, paired posterior myodomes, a deep, transverse fossa in the posterodorsal part of the orbit, and a feeding mechanism structured for durophagy. Phylogenetic analysis places Yelangichthys gen. nov. at the most basal position in the Saurichthyiformes as the sister to Saurichthyidae, and a new family Yelangichthyidae is erected to include only Y. macrocephalus gen. et sp. nov. The monophyly of the Chondrostei comprising [Saurichthyiformes + Acipenseriformes] Birgeriiformes is supported, but not the monophyly of Saurichthys, the type genus of Saurichthyidae. With its outstanding osteological details, Yelangichthys gen. nov. greatly increases the neurocranial variations in saurichthyiforms, and its novel feeding structure suggests the consumption of hard-preys instead of fishes.Conclusions/significanceOur findings highlight the detailed osteology of a saurichthyiform braincase and its feeding design. We suggest that saurichthyiforms are closely allied to the Acipenseriformes. Saurichthyiforms were very diverse in the cranial osteology and they might have undergone a rapid evolutionary radiation via, for the new material here, transforming the feeding mechanism and thus exploiting the food resources unsuitable for other saurichthyiforms.

The article is a response to criticisms of a previous study on avian species trees. The authors argue that the criticisms are unfounded and stem from subjective opinions and misconceptions of phylogenetic analysis. They defend the accuracy of their method, NJst, and highlight its alignment with other reliable methods. They also address concerns about data misalignments and the presence of paralogs, asserting that these factors have minimal impact on phylogenetic analysis. The authors conclude that their analysis demonstrates the robustness of NJst and refute the claims made by the critics. [Extracted from the article]

The phylogeny and divergence timing of the Neoavian radiation remain controversial despite recent progress. We analyzed the genomes of 124 species across all Neoavian orders, using data from 25,460 loci spanning four DNA classes, including 5,756 coding sequences, 12,449 conserved nonexonic elements, 4,871 introns, and 2,384 intergenic segments. We conducted a comprehensive sensitivity analysis to account for the heterogeneity across different DNA classes, leading to an optimal tree of Neoaves with high resolution. This phylogeny features a novel Neoavian dichotomy comprising two monophyletic clades: a previously recognized Telluraves (land birds) and a newly circumscribed Aquaterraves (waterbirds and relatives). Molecular dating analyses with 20 fossil calibrations indicate that the diversification of modern birds began in the Late Cretaceous and underwent a constant and steady radiation across the KPg boundary, concurrent with the rise of angiosperms as well as other major Cenozoic animal groups including placental and multituberculate mammals. The KPg catastrophe had a limited impact on avian evolution compared to the Paleocene-Eocene Thermal Maximum, which triggered a rapid diversification of seabirds. Our findings suggest that the evolution of modern birds followed a slow process of gradualism rather than a rapid process of punctuated equilibrium, with limited interruption by the KPg catastrophe. This study places bird evolution into a new context within vertebrates, with ramifications for the evolution of the Earth's biota. [ABSTRACT FROM AUTHOR]