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Aqueous zinc ion batteries (AZIBs) have emerged as promising candidates for large-scale energy storage systems during post lithium-ion era, drawing attention for their environmental-friendliness, cost-effectiveness, high safety, and minimal manufacturing constraints. However, the long-standing roadblock to their commercialization lies in the dendrite growth and parasitic reactions (hydrogen evolution reaction and water-induced corrosion) of the metallic zinc anode, which strongly depends on the complicated interphasial chemistries. This review, with a focus on optimizing the zinc anode/electrolyte interphase, begins by elucidating the intrinsic factor of zinc ions’ migration, diffusion, nucleation, electro-crystallization, and growth of the zinc nucleus in AZIBs, along with the underlying scientific principles. Then the electrochemical theories pertinent to the plating behavior of the interphase is systematically clarified, thereby enriching the understanding of how anode structure and electrolyte design principles relate to the electrode interphase. Accordingly, the rational strategies emphasizing structural engineering of the zinc anode and electrolyte have been summarized and discussed in detail. The mechanisms, advances, drawbacks, and future outlook of these strategies are analyzed for the purpose of fabricating a chemically and electrochemically stable interphase. Finally, the challenging perspectives and major directions of zinc anode are proposed. This review is expected to shed light on developing high-performance Zn anodes for use in sustainable AZIBs.

Objective: DNA damage response (DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation (DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor (ICI) therapy in gastrointestinal (GI) cancer. Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts. Results: The DRIA signature includes three genes (CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients (81.8% vs. 8.8%; P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve (AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer. Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pan-cancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

Abstract The lack of efficient biomarkers for the early detection of gastric cancer (GC) contributes to its high mortality rate, so it is crucial to discover novel diagnostic targets for GC. Recent studies have implicated the potential of site‐specific glycans in cancer diagnosis, yet it is challenging to perform highly reproducible and sensitive glycoproteomics analysis on large cohorts of samples. Here, a highly robust N‐glycoproteomics (HRN) platform comprising an automated enrichment method, a stable microflow LC‐MS/MS system, and a sensitive glycopeptide‐spectra‐deciphering tool is developed for large‐scale quantitative N‐glycoproteome analysis. The HRN platform is applied to analyze serum N‐glycoproteomes of 278 subjects from three cohorts to investigate glycosylation changes of GC. It identifies over 20 000 unique site‐specific glycans from discovery and validation cohorts, and determines four site‐specific glycans as biomarker candidates. One candidate has branched tetra‐antennary structure capping with sialyl‐Lewis antigen, and it significantly outperforms serum CEA with AUC values > 0.89 compared against < 0.67 for diagnosing early‐stage GC. The four‐marker panel can provide improved diagnostic performances. Besides, discrimination powers of four candidates are also testified with a verification cohort using PRM strategy. This findings highlight the value of this strong tool in analyzing aberrant site‐specific glycans for cancer detection.

Background The effectiveness of immune checkpoint inhibitors in colorectal cancer (CRC) is limited due to the low tumor neoantigen load and low immune infiltration in most microsatellite-stable (MSS) tumors. This study aimed to develop a mitochondria-targeted photodynamic therapy (PDT) approach to provoke host antitumor immunity of MSS-CRC and elucidate the underlying molecular mechanisms.Methods The role and mechanism of mitochondria-targeted PDT in inhibiting CRC progression and inducing pyroptosis were evaluated both in vitro and in vivo. The immune effects of PDT sensitization on PD-1 blockade were also assessed in CT26 and 4T1 tumor-bearing mouse models.Results Here, we report that PDT using IR700DX-6T, a photosensitizer targeting the mitochondrial translocation protein, may trigger an antitumor immune response initiated by pyroptosis in CRC. Mechanistically, IR700DX-6T-PDT produced reactive oxygen species on light irradiation and promoted downstream p38 phosphorylation and active caspase3 (CASP3)-mediated cleavage of gasdermin E (GSDME), subsequently inducing pyroptosis. Furthermore, IR700DX-6T-PDT enhanced the sensitivity of MSS-CRC cells to PD-1 blockade. Decitabine, a demethylation drug used to treat hematologic neoplasms, disrupted the abnormal methylation pattern of GSDME in tumor cells, enhanced the efficacy of IR700DX-6T-PDT, and elicited a potent antitumor immune response in combination with PD-1 blockade and IR700DX-6T-PDT.Conclusion Our work provides clear a understanding of immunogenic cell death triggered by mitochondria-targeted PDT, offering a new approach for enhancing the efficacy of PD-1 blockade in CRC.

Abstract Mechanosensitive mechanisms are often used to sense damage to tissue structure, stimulating matrix synthesis and repair. While this kind of mechanoregulatory process is well recognized in eukaryotic systems, it is not known whether such a process occurs in bacteria. In Vibrio cholerae, antibiotic-induced damage to the load-bearing cell wall promotes increased signaling by the two-component system VxrAB, which stimulates cell wall synthesis. Here we show that changes in mechanical stress within the cell envelope are sufficient to stimulate VxrAB signaling in the absence of antibiotics. We applied mechanical forces to individual bacteria using three distinct loading modalities: extrusion loading within a microfluidic device, direct compression and hydrostatic pressure. In all cases, VxrAB signaling, as indicated by a fluorescent protein reporter, was increased in cells submitted to greater magnitudes of mechanical loading, hence diverse forms of mechanical stimuli activate VxrAB signaling. Reduction in cell envelope stiffness following removal of the endopeptidase ShyA led to large increases in cell envelope deformation and substantially increased VxrAB response, further supporting the responsiveness of VxrAB. Our findings demonstrate a mechanosensitive gene regulatory system in bacteria and suggest that mechanical signals may contribute to the regulation of cell wall homeostasis.

Background: Bedside freehand catheter insertion for the treatment of basal ganglia hemorrhage currently remains the major method due to its simplicity and efficiency, but it is associated with low precision. We retrospectively evaluated the feasibility and accuracy of using a wearable mixed-reality holographic computer to guide catheter-based basal ganglia hemorrhage treatment compared to the freehand method. Methods: We collected 30 patients who initially underwent either mixed-reality holographic guided catheter insertion (holographic guidance group) or freehand catheter insertion (freehand group). Data of pre- and postoperative CT images in both groups and surgical plans of the holographic guidance group were retrieved from the database. The additional time for holographic guidance was quantified. For both groups, we calculated the number of cases in which the catheter tip was initially outside the hematoma and the number of times for catheter repositioning. Catheter insertion accuracy was quantitatively evaluated using the target deviation. Results: The average additional time required for holographic guidance was 36.65 ± 15.18 min. In the holographic guidance group, all the cases had catheter tips initially inside the hematoma, and none of them needed catheter repositioning. In the freehand group, 3 cases had their catheter tips initially outside the hematoma, and 5 catheter repositioning procedures were performed. The mean target deviation was 5.46 ± 2.22 mm in the holographic guidance group and 12.57 ± 6.77 mm in the freehand group (p

Abstract Optogenetics tools for precise temporal and spatial control of protein abundance are valuable in studying diverse complex biological processes. In the present study, we engineer a monomeric tag of stabilization upon light induction (SULI) for yeast and zebrafish based on a single light-oxygen-voltage domain from Neurospora crassa. Proteins of interest fused with SULI are stable upon light illumination but are readily degraded after transfer to dark conditions. SULI shows a high dynamic range and a high tolerance to fusion at different positions of the target protein. Further studies reveal that SULI-mediated degradation occurs through a lysine ubiquitination-independent proteasome pathway. We demonstrate the usefulness of SULI in controlling the cell cycle in yeast and regulating protein stability in zebrafish, respectively. Overall, our data indicate that SULI is a simple and robust tool to quantitatively and spatiotemporally modulate protein levels for biotechnological or biomedical applications.

Hematite is one of the most promising photoanode materials for the study of photoelectrochemical (PEC) water splitting because of its ideal bandgap with sufficient visible light absorption and stability in alkaline electrolytes. However, owing to the intrinsically high electron-hole recombination, the PEC performance of hematite is still far below that expected. The efficient charge separation can be achieved via growth of FeOOH on hematite photoanode. In this study, hematite nanostructures were successfully grown on the surface of iron foil by the simple immersion deposition method and thermal oxidation treatment. Furthermore, cocatalyst FeOOH was successfully added to the hematite nanostructure surface to improve charge separation and charge transfer, and thus promote the photoelectrochemical water splitting. By utilizing the FeOOH overlayer as a cocatalyst, the photocurrent density of hematite exhibited a substantial 86% increase under 1.5 VRHE, while the onset potential showed an apparent shift towards the cathodic direction. This can be ascribed to the high reaction area for the nanostructured morphology and high electrocatalytic activity of FeOOH that enhanced the amount of photogenerated holes and accelerated the kinetics of water splitting.

Metallic zinc is an ideal anode material for aqueous rechargeable batteries but reversibility is a challenge. Here, the authors realise a dynamic real-time reconstructed interphase on zinc anode formed by graphitic carbon nitride quantum dot as an electrolyte additive to improve the performance of Zn metal anodes.

Two-dimensional (2D) materials have attracted considerable attention due to their potential for generating ultrafast pulsed lasers. Unfortunately, the poor stability of most layered 2D materials under air exposure leads to increased fabrication costs; this has limited their development for practical applications. In this paper, we describe the successful preparation of a novel, air-stable, and broadband saturable absorber (SA), the metal thiophosphate CrPS4, using a simple and cost-effective liquid exfoliation method. The van der Waals crystal structure of CrPS4 consists of chains of CrS6 units interconnected by phosphorus. In this study, we calculated the electronic band structures of CrPS4, revealing a direct band gap. The nonlinear saturable absorption properties, which were investigated using the P-scan technique at 1550 nm, revealed that CrPS4-SA had a modulation depth of 12.2% and a saturation intensity of 463 MW/cm2. Integration of the CrPS4-SA into Yb-doped fiber and Er-doped fiber laser cavities led to mode-locking for the first time, resulting in the shortest pulse durations of 298 ps and 500 fs at 1 and 1.5 µm, respectively. These results indicate that CrPS4 has great potential for broadband ultrafast photonic applications and could be developed into an excellent candidate for SA devices, providing new directions in the search for stable SA materials and for their design.

To meet the requirements of deployable structures in aerospace engineering with light weight and high stiffness, this paper proposes the triangular space membrane deployable mechanism based on deployable booms, then conducts dynamic analysis and multiobjective optimization. The configuration design and mass calculation for the membrane mechanism are carried out, including its unfolding support mechanism and tensioned membrane scheme. With a view to performing the dynamic characteristics analysis and parametric studies, the finite element simulation model of the membrane mechanism, including boom, cable and membrane, is built and validated against test results obtained by Polytec. On the basis of the simulation results, a surrogate model of fundamental frequency is established by adopting the response surface method and applied to multiobjective optimization combined with the mass formula. Then, the optimal dynamic and lightweight design parameters are solved via the genetic algorithm. The results provide an indication to aid with the design and analysis of space membrane deployable mechanisms according to the required properties and space mission requirements.

Adjusting the roll angle of a rover’s body is a commonly used strategy to improve its traversability over sloped terrains. However, its range of adjustment is often limited, due to constraints imposed by the rover design and geometry factors such as suspension, chassis, size, and suspension travel. In order to improve the rover’s traversability under these constraints, this paper proposes a reconfigurable rover design with a two-level (sliding and rolling) mechanism to adjust the body’s roll angle. Specifically, the rolling mechanism is a bionic structure, akin to the human ankle joint which can change the contact pose between the wheel and the terrain. This novel adjustment mechanism can modulate the wheel–terrain contact pose, center-of-mass projection over the supporting polygon, wheel load, and the rover driving mode. Combining the wheel–load model and terramechanics-based wheel–terrain interaction model, we develop an integrated model to describe the system dynamics, especially the relationship between rover pose and wheel slippage parameters. Using this model, we develop an associated attitude control strategy to calculate the desired rover pose using particle swarm algorithm while considering the slip rate and angle constraints. We then adjust the sliding and rolling servo angles accordingly for slope traversing operations. To evaluate the proposed design and control strategies, we conduct extensive simulation and experimental studies. The results indicate that our proposed rover design and associated control strategy can double the maximum slope angles that the rover can negotiate, resulting in significantly improved traversability over soft sloped terrains.

As a deubiquitination (DUB) enzyme, ubiquitin-specific protease 13 (USP13) is involved in a myriad of cellular processes, such as mitochondrial energy metabolism, autophagy, DNA damage response, and endoplasmic reticulum-associated degradation (ERAD), by regulating the deubiquitination of diverse key substrate proteins. Thus, dysregulation of USP13 can give rise to the occurrence and development of plenty of diseases, in particular malignant tumors. Given its implications in the stabilization of disease-related proteins and oncology targets, considerable efforts have been committed to the discovery of inhibitors targeting USP13. Here, we summarize an overview of the recent advances of the structure, function of USP13, and its relations to diseases, as well as discovery and development of inhibitors, aiming to provide the theoretical basis for investigation of the molecular mechanism of USP13 action and further development of more potent druggable inhibitors.

De novo and acquired resistance are major impediments to the efficacy of conventional and targeted cancer therapy. In unselected gastric cancer (GC) patients with advanced disease, trials combining chemotherapy and an anti-EGFR monoclonal antibody have been largely unsuccessful. In an effort to identify biomarkers of resistance so as to better select patients for such trials, we screened the secretome of chemotherapy-treated human GC cell lines. We found that levels of CGA, the α-subunit of glycoprotein hormones, were markedly increased in the conditioned media of chemoresistant GC cells, and CGA immunoreactivity was enhanced in GC tissues that progressed on chemotherapy. CGA levels in plasma increased in GC patients who received chemotherapy, and this increase was correlated with reduced responsiveness to chemotherapy and poor survival. Mechanistically, secreted CGA was found to bind to EGFR and activate EGFR signaling, thereby conferring a survival advantage to GC cells. N-glycosylation of CGA at Asn52 and Asn78 is required for its stability, secretion, and interaction with EGFR. GATA2 was found to activate CGA transcription, whose increase, in turn, induced the expression and phosphorylation of GATA2 in an EGFR-dependent manner, forming a positive feedback circuit that was initiated by GATA2 autoregulation upon sublethal exposure to chemotherapy. Based on this circuit, combination strategies involving anti-EGFR therapies or targeting CGA with microRNAs (miR-708-3p and miR-761) restored chemotherapy sensitivity. These findings identify a clinically actionable CGA/EGFR/GATA2 circuit and highlight CGA as a predictive biomarker and therapeutic target in chemoresistant GC.

As one of the primary therapeutic choices, chemotherapy is widely adopted for progressive gastric cancer (GC), but the development of chemoresistance has limited chemotherapy efficacy and partly contributes to poor prognosis. Immunotherapy is increasingly being applied in the clinical treatment of GC and is also benefitting patients. To ascertain whether ATXN2 affects chemotherapy efficacy in GC cells and its role in GC immune escape, we performed high-throughput sequencing to clarify genes differentially expressed between 5-FU-resistant and 5-FU-sensitive GC cells and then conducted qRT–PCR to assess ATXN2 expression in GC tissues. Furthermore, the influence of ATXN2 on resistance was studied in vitro and in vivo, ATXN2 and other protein expression levels were detected using Western blotting and immunohistochemistry (IHC), and the direct association of SP1 and ATXN2 was confirmed through luciferase reporter gene analysis. We found elevated ATXN2 in GC tumors and a negative correlation between ATXN2 levels and the prognosis of GC. Furthermore, by activating the PI3K/AKT pathway, ATXN2 was found to promote chemoresistance in GC, facilitating BCL2L1 expression. In GC cells, ATXN2 further stimulated PD-L1 expression and provided better immunotherapy efficacy. Finally, we demonstrated that SP1 transcriptionally regulated the expression of ATXN2 and prompted GC chemoresistance and immune escape. In conclusion, our study reveals the important roles of the SP1/ATXN2/PI3K-AKT/BCL2L1 signalling pathway in GC chemoresistance and of the SP1/ATXN2/PI3K-AKT/PD-L1 signalling pathway in GC immunotherapy. Our findings provide new theories and experimental references for overcoming chemotherapy resistance in GC and enhancing the efficacy of immunotherapy for GC.

Nitrogen–fixing bacteria execute biological nitrogen fixation through nitrogenase, converting inert dinitrogen (N2) in the atmosphere into bioavailable nitrogen. Elaborating the molecular mechanisms of orderly and efficient biological nitrogen fixation and applying them to agricultural production can alleviate the “nitrogen problem”. Azotobacter vinelandii is a well–established model bacterium for studying nitrogen fixation, utilizing nitrogenase encoded by the nif gene cluster to fix nitrogen. In Azotobacter vinelandii, the NifA–NifL system fine–tunes the nif gene cluster transcription by sensing the redox signals and energy status, then modulating nitrogen fixation. In this manuscript, we investigate the transcriptional regulation mechanism of the nif gene in autogenous nitrogen–fixing bacteria. We discuss how autogenous nitrogen fixation can better be integrated into agriculture, providing preliminary comprehensive data for the study of autogenous nitrogen–fixing regulation.

Abstract Understanding and exploring the functional modules (FMs) consisting of local atomic groups can promote the development of the materials with functional performances. Oxygen‐containing tetrahedral modules are popular in deep‐ultraviolet (DUV) optical materials, but their weak optical anisotropy is adverse to birefringence. Here, the fluorooxosulfate group is proved as a new birefringence‐enhanced FM for the first time. The birefringence of fluorooxosulfates can be 4.8–15.5 times that of sulfates with the same metal cations while maintaining a DUV band gap. The polarizing microscope measurement confirms the birefringence enhancement by using the millimeter crystals experimentally. The theoretical studies from micro and macro levels further reveal a novel universal strategy that the fluorine induced anisotropic electronic distribution in fluorooxo–tetrahedral group is responsible for the enhancement of birefringence. This study will guide the future discovery of DUV optical materials with enlarged birefringence.

Under the new normal of economy, the relationship between economic benefits and company’s environmental behavior (green behavior) has long been the focus of scholars’ research, but less attention has been paid to the effect of financial performance on company’s green behavior in China as a developing country. Thus, by adopting a mixed methodology, we conduct a quantitative study by selecting 228 companies as samples with good and poor green behavior for comparative analysis, followed by a qualitative study of 20 specific cases, to analyse the complex relationship mechanism of how financial performance in terms of business solvency, profitability, and development ability affect company’s green behavior. The results indicate that business solvency, profitability, and development ability are strongly associated with company’s green behavior, respectively. This study contributes to the green behavior literature.

Chiroptical switches have found application in the detection of a multitude of different analytes with a high level of sensitivity and in asymmetric catalysis to offer switchable stereoselectivity. A wide range of scaffolds have been employed that respond to metals, small molecules, anions and other analytes. Not only have chiroptical systems been used to detect the presence of analytes, but also other properties such as oxidation state and other physical phenomena that influence helicity and conformation of molecules and materials. Moreover, the tunable responses of many such chiroptical switches enable them to be used in the controlled production of either enantiomer or diastereomer at will in many important organic reactions from a single chiral catalyst through selective use of a low-cost inducer: Co-catalysts (guests), metal ions, counter ions or anions, redox agents or electrochemical potential, solvents, mechanical forces, temperature or electromagnetic radiation.

Dynamic characteristics of electroosmosis of a typical non-Newtonian liquid in a rectangular microchannel are investigated by using numerical simulations. The non-Newtonian behavior of liquids is assumed to obey the famous power-law model and then the mathematical model is solved numerically by using the finite element method. The results indicate that the non-Newtonian effect produces some noticeable dynamic responses in electroosmotic flow. Under a direct current (DC) driving electric field, it is found that the fluid responds more inertly to an external electric field and the steady-state velocity profile becomes more plug-like as the flow behavior index decreases. Under an alternating current (AC) driving electric field, the fluid is observed to experience more significant acceleration and the amplitude of oscillating velocity becomes larger as the fluid behavior index decreases. Furthermore, our investigation also shows that electroosmotic flow of power-law fluids under an AC/DC combined driving field is enhanced as compared with that under a pure DC electric field. These dynamic predictions are of practical use for the design of electroosmotically-driven microfluidic devices that analyze and process non-Newtonian fluids such as biofluids and polymeric solutions.

Corrosion of reinforced concrete structures has become a major problem worldwide, leading to very high repair costs. A dearth of studies has focused on the corrosion damage evolution of reinforced concrete. In this paper, the ultrasonic guided wave (UGW) technique is adopted to monitor the reinforced concrete corrosion damage evolution process. The properties of different guide wave modes were studied by steel rebar dispersion curves of UGWs through numerical calculation. The availability and validity of the UGW testing-reinforced concrete corrosion damage is proved by corrosion experiment. The experiment shows that the first wave peak value could describe the whole process of steel rebar corrosion. As the corrosion damage level increases, the relative variation for the first UGW peak value increases first and then decreases.

Human quiescin-sulfhydryl oxidase 1 isoform b (HsQSOX1b) is a highly efficient, multiple-domain enzyme that directly inserts disulfide bonds into client protein. However, previous studies have focused mainly on the catalytic activity of the whole protein rather than its domain structure. In this research, we dissected the structure and function of HsQSOX1b and explored its mechanism as a highly efficient sulfhydryl oxidase by analyzing the truncated variants. The results showed that the first HsQSOX1b thioredoxin domain was essential for thiol oxidase activity. The smallest active fragment (SAQ) was identified to consist of a helix-rich region (HRR) and an essential for respiration and viability/augmenter of liver regeneration (ERV/ALR) domain, which remained highly active to oxidize an artificial non-thiol substrate but not small molecular and protein thiols. Our study clearly demonstrated that SAQ is a highly efficient oxidative engine, which shows high efficiency in the de novo disulfide formation and oxygen reduction and that this more efficient oxidative engine is necessary for the highly efficient catalysis of QSOXs compared to Erv1 and Erv2. This study will help address the roles of different HsQSOX1b domains in de novo disulfide formation and encourage the engineering of more efficient QSOX variants for the in vitro folding of disulfide-containing proteins.

In this paper, a Bi-angle Model Management method (BiMM) is proposed to manage models in virtual reality research. One angle is based on the model itself, which includes the model, model scheme, and texture; another angle is based on the model sort - each sort has its child sorts except leaf nodes. Based on this method, we have developed a model management application that has the following major functions: model management, model sort management, model query, model statistics, model registration into database as a whole, etc. With this method, researchers can manage model data conveniently and efficiently.