Nitrogen deposition differentially regulates the sensitivity of gross primary productivity to extreme drought versus wetness.

Global hydroclimatic variability is increasing with more frequent extreme dry and wet years, severely destabilizing terrestrial ecosystem productivity. However, what regulates the consequence of precipitation extremes on productivity remains unclear. Based on a 9-year field manipulation experiment on the Qinghai-Tibetan Plateau, we found that the responses of gross primary productivity (GPP) to extreme drought and wetness were differentially regulated by nitrogen (N) deposition. Over increasing N deposition, extreme dry events reduced GPP more. Among the 12 biotic and abiotic factors examined, this was mostly explained by the increased plant canopy height and proportion of drought-sensitive species under N deposition, making photosynthesis more sensitive to hydraulic stress. While extreme wet events increased GPP, their effect did not shift over N deposition. These site observations were complemented by a global synthesis derived from the GOSIF GPP dataset, which showed that GPP sensitivity to extreme drought was larger in ecosystems with higher N deposition, but GPP sensitivity to extreme wetness did not change with N deposition. Our findings indicate that intensified hydroclimatic variability would lead to a greater loss of land carbon sinks in the context of increasing N deposition, due to that GPP losses during extreme dry years are more pronounced, yet without a synchronous increase in GPP gains during extreme wet years. The study implies that the conservation and management against climate extremes merit particular attention in ecosystems subject to N deposition.

Anus preservation in low rectal adenocarcinoma based on MMR/MSI status (APRAM): a study protocol for a randomised, controlled, open-label, multicentre phase III trial.

BACKGROUND: Anus preservation has been a challenge in the treatment of patients with low rectal adenocarcinoma (within 5 cm from the anal verge) because it is difficult to spare the anus with its functioning sphincter complex under the safe margin of tumour resection. Patients with dMMR/MSI-H can achieve a favourable complete response (CR) rate by using a single immune checkpoint inhibitor. For patients with pMMR/MSS/MSI-L, intensified neoadjuvant three-drug chemotherapy may be the preferred option for anal preservation. In addition, the watch and wait (W&W) strategy has been proven safe and feasible for patients with rectal cancer who achieve a clinical complete response (cCR). Therefore, we initiated this clinical trial to explore the optimal neoadjuvant treatment pattern for patients with low locally advanced rectal cancer (LARC) with different MMR/MSI statuses, aiming to achieve a higher cCR rate with the W&W strategy and ultimately provide more patients with a chance of anus preservation. METHODS: This is a randomised, controlled, open-label, multicentre phase III trial. Patients with clinical stage T2-4 and/or N + tumours located within 5 cm from the anal verge are considered eligible. Based on the results of pathological biopsy, the patients are divided into two groups: dMMR/MSI-H and pMMR/MSS. Patients in the dMMR/MSI-H group will be randomly allocated in a 1:1 ratio to either arm A (monoimmunotherapy) or arm B (short-course radiotherapy followed by monoimmunotherapy). Patients in the pMMR/MSS group will be initially treated with long-term pelvic radiation with concurrent capecitabine combined with irinotecan. Two weeks after the completion of chemoradiotherapy (CRT), the patients will be randomly allocated in a 1:1 ratio to arm C (XELIRI six cycle regime) or arm D (FOLFIRINOX nine cycle regime). The irinotecan dose will be adjusted according to the UGT1A1-genotype. After treatment, a comprehensive assessment will be performed to determine whether a cCR has been achieved. If achieved, the W&W strategy will be adopted; otherwise, total mesorectal excision (TME) will be performed. The primary endpoint is cCR with the maintenance of 12 months at least, determined using digital rectal examination, endoscopy, and rectal MRI or PET/CT as a supplementary method. DISCUSSION: APRAM will explore the best anus preservation model for low LARC, combining the strategies of consolidation chemotherapy, immunotherapy, and short-course radiotherapy, and aims to preserve the anus of more patients using W&W. Our study provides an accurate individual treatment mode based on the MMR/MSI status for patients with low LARC, and more patients will receive the opportunity for anus preservation under our therapeutic strategy, which would transform into long-term benefits. TRIAL REGISTRATION: Clinicaltrials.gov NCT05669092 (Registered 28th Nov 2022).

Effects of Mineralocorticoid Receptor Antagonists for Chronic Kidney Disease: A Systemic Review and Meta-Analysis.

BACKGROUND: Mineralocorticoid receptor blockade could be a potential approach for the inhibition of chronic kidney disease (CKD) progression. The benefits and harms of different mineralocorticoid receptor antagonists (MRAs) in CKD are inconsistent. OBJECTIVES: The aim of the study was to summarize the benefits and harms of MRAs for CKD patients. METHODS: We searched MEDLINE, EMBASE, and the Cochrane databases for trials assessing the effects of MRAs on non-dialysis-dependent CKD populations. Treatment and adverse effects were summarized using meta-analysis. RESULTS: Fifty-three trials with 6 different MRAs involving 22,792 participants were included. Compared with the control group, MRAs reduced urinary albumin-to-creatinine ratio (weighted mean difference [WMD], -90.90 mg/g, 95% CI, -140.17 to -41.64 mg/g), 24-h urinary protein excretion (WMD, -0.20 g, 95% CI, -0.28 to -0.12 g), estimated glomerular filtration rate (eGFR) (WMD, -1.99 mL/min/1.73 m2, 95% CI, -3.28 to -0.70 mL/min/1.73 m2), chronic renal failure events (RR, 0.86, 95% CI, 0.79-0.93), and cardiovascular events (RR, 0.84, 95% CI, 0.77-0.92). MRAs increased the incidence of hyperkalemia (RR, 2.04, 95% CI, 1.73-2.40) and hypotension (RR, 1.80, 95% CI, 1.41-2.31). MRAs reduced the incidence of peripheral edema (RR, 0.65, 95% CI, 0.56-0.75) but not the risk of acute kidney injury (RR, 0.94, 95% CI, 0.79-1.13). Nonsteroidal MRAs (RR, 0.66, 95% CI, 0.57-0.75) but not steroidal MRAs (RR, 0.20, 95% CI, 0.02-1.68) significantly reduced the risk of peripheral edema. Steroidal MRAs (RR, 5.68, 95% CI, 1.26-25.67) but not nonsteroidal MRAs (RR, 0.52, 95% CI, 0.22-1.22) increased the risk of breast disorders. CONCLUSIONS: In the CKD patients, MRAs, particularly in combination with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, reduced albuminuria/proteinuria, eGFR, and the incidence of chronic renal failure, cardiovascular and peripheral edema events, whereas increasing the incidence of hyperkalemia and hypotension, without the augment of acute kidney injury events. Nonsteroidal MRAs were superior in the reduction of more albuminuria with fewer peripheral edema events and without the augment of breast disorder events.

Multiple-cycle photochemical cascade reactions.

Cascade reactions represent an efficient and economical synthetic approach, enabling the rapid synthesis of a wide array of structurally complex organic compounds. These compounds, previously inaccessible, can now be synthesized in a remarkably limited number of steps. Concurrently, the photochemical reactions of organic molecules have gained prominence as a potent strategy for accessing a diverse range of radical species and intermediates. This is achieved in a controlled manner under mild conditions. Owing to the relentless endeavors of chemists, significant strides have been made in the realm of photochemical cascade reactions. These advancements have facilitated the synthesis of novel molecular structures with high complexity, structures that are typically challenging to generate under thermal conditions. In this review, we comprehensively summarize and underscore the recent pivotal advancements in visible-light-induced cascade reactions. Our focus is on the elucidation of multiple photochemical catalytic cycles, emphasizing the catalytic activation modes and the types of reactions involved.

Alkaline phosphatase-activated prodrug system based on a bifunctional CuO NP tandem nanoenzyme for on-demand bacterial inactivation and wound disinfection.

Nanozymes are promising antimicrobials, as they produce reactive oxygen species (ROS). However, the intrinsic lack of selectivity of ROS in distinguishing normal flora from pathogenic bacteria deprives nanozymes of the necessary selectivities of ideal antimicrobials. Herein, we exploit the physiological conditions of bacteria (high alkaline phosphatase (ALP) expression) using a novel CuO nanoparticle (NP) nanoenzyme system to initiate an ALP-activated ROS prodrug system for use in the on-demand precision killing of bacteria. The prodrug strategy involves using 2-phospho-L-ascorbic acid trisodium salt (AAP) that catalyzes the ALP in pathogenic bacteria to generate ascorbic acid (AA), which is converted by the CuO NPs, with intrinsic ascorbate oxidase- and peroxidase-like activities, to produce ROS. Notably, the prodrug system selectively kills Escherichia coli (pathogenic bacteria), with minimal influence on Staphylococcus hominis (non-pathogenic bacteria) due to their different levels of ALP expression. Compared to the CuO NPs/AA system, which generally depletes ROS during storage, CuO NPs/AAP exhibits a significantly higher stability without affecting its antibacterial activity. Furthermore, a rat model is used to indicate the applicability of the CuO NPs/AAP fibrin gel in wound disinfection in vivo with negligible side effects. This study reveals the therapeutic precision of this bifunctional tandem nanozyme platform against pathogenic bacteria in ALP-activated conditions.

Targeting novel inhibitory receptors in cancer immunotherapy.

T cells play a critical role in promoting tumor regression in both experimental models and humans. Yet, T cells that are chronically exposed to tumor antigen during cancer progression can become dysfunctional/exhausted and fail to induce tumor destruction. Such tumor-induced T cell dysfunction may occur via multiple mechanisms. In particular, immune checkpoint inhibitory receptors that are upregulated by tumor-infiltrating lymphocytes in many cancers limit T cell survival and function. Overcoming this inhibitory receptor-mediated T cell dysfunction has been a central focus of recent developments in cancer immunotherapy. Immunotherapies targeting inhibitory receptor pathways such as programmed cell death 1 (PD-1)/programmed death ligand 1 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), alone or in combination, confer significant clinical benefits in multiple tumor types. However, many patients with cancer do not respond to immune checkpoint blockade, and dual PD-1/CTLA-4 blockade may cause serious adverse events, which limits its indications. Targeting novel non-redundant inhibitory receptor pathways contributing to tumor-induced T cell dysfunction in the tumor microenvironment may prove efficacious and non-toxic. This review presents preclinical and clinical findings supporting the roles of two key pathways-T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) and T cell immunoreceptor with Ig and ITIM domain (TIGIT)/CD226/CD96/CD112R-in cancer immunotherapy.

Confinement of Organic Dyes in UiO-66-Type Metal-Organic Frameworks for the Enhanced Synthesis of [1,2,5]Thiadiazole[3,4-g]benzoimidazoles.

Organic dyes as non-noble metal photosensitizers have attracted increasing attention due to their environmental friendliness and sustainability but suffer from fast deactivation and low stability. Here, we reported a fruitful strategy by the confinement and stabilization of visible light-active signal unit organic dyes within the metal-organic frameworks (MOFs) and developed a series of heterogeneous photocatalysts dye@UiO-66s [dye = fluorescein (FL)/rhodamine B (RhB)/eosin Y (EY), UiO-66s = UiO-66, and Bim-UiO-66]. It has been demonstrated that the encapsulated dyes can effectively sensitize MOF hosts and dominate the band structures and photocatalytic activities of dye@UiO-66s regardless of the ligand functionalization of MOFs. Photocatalytic experiments showed that these dye@UiO-66s exhibit enhanced activities relative to free dyes and among them, FL@Bim-UiO-66 displays excellent efficiencies toward the green synthesis of new carbon-bridged annulations, [1,2,5]thiadiazole[3,4-g]benzoimidazoles in the yield of up to 98% at room temperature with outstanding stability and reusability. Furthermore, the intramolecular cyclization intermediate was captured and characterized by the single-crystal X-ray diffraction analysis.

Controlling Surface Chemical Inhomogeneity of Ni2 P/MoNiP2 /MoP Heterostructure Electrocatalysts for Efficient Hydrogen Evolution Reaction.

Crystalline/amorphous phase engineering is demonstrated as a powerful strategy for electrochemical performance optimization. However, it is still a considerable challenge to prepare transition metal-based crystalline/amorphous heterostructures because of the low redox potential of transition metal ions. Herein, a facile H2 -assisted method is developed to prepare ternary Ni2 P/MoNiP2 /MoP crystalline/amorphous heterostructure nanowires on the conductive substrate. The characterization results show that the content of the MoNiP2 phase and the crystallinity of the MoP phase can be tuned by simply controlling the H2 concentration. The obtained electrocatalyst exhibits a superior alkaline hydrogen evolution reaction performance, delivering overpotentials of 20 and 76 mV to reach current densities of 10 and 100 mA cm-2 with a Tafel slope of 30.6 mV dec-1 , respectively. The catalysts also reveal excellent stability under a constant 100 h operation, higher than most previously reported electrocatalysts. These striking performances are ascribed to the optimized hydrogen binding energy and favorable hydrogen adsorption/desorption kinetics. This work not only exhibits the potential application of ternary Ni2 P/MoNiP2 /MoP crystalline/amorphous heterostructure nanowires catalysts for practical electrochemical water splitting, but also paves the way to prepare non-noble transition metal-based electrocatalysts with optimized crystalline/amorphous heterostructures.

Incorporating a D-A-D-Type Benzothiadiazole Photosensitizer into MOFs for Photocatalytic Oxidation of Phenylsulfides and Benzylamines.

Oxidation and removal of highly toxic sulfides and amines are particularly important for environmental and human security but remain challenging. Here, incorporating an excellent photosensitizer, donor-acceptor-donor (D-A-D)-type 4,4'-(benzo[c][1,2,5]thiadiazole-4,7-diyl)dibenzoic (H2L), into metal-organic frameworks (MOFs) has been manifested to promote the charge separation, affording four three-dimensional (3D) MOFs (isostructural 1-Co/1-Zn with Co2/Zn2 units, and 2-Gd/2-Tb with Gd/Tb-cluster chains) as photocatalysts in the visible light-driven air-O2-mediated catalytic oxidation and removal of hazardous phenylsulfides and benzylamines. Impressively, structure-property correlation illustrated that the transition metal centers assembled in MOFs play an important role in the photocatalytic activity, and we can conclude that 1-Zn can be a robust heterogeneous catalyst possessing good light adsorption and fast charge separation in oxidation removal reactions of both benzylamines and phenylsulfides under visible light irradiation and room temperature with excellent activity/selectivity, stability, and reusability.

The crucial value of serum ferritin in assessing high-risk factors and prognosis for patients with endometrial carcinoma.

BACKGROUND: Endometrial carcinoma is a common malignant tumor in female reproductive system. At present, there is no effective and economic prognostic index. This study aimed to investigate the effect of serum ferritin levels on the prognosis of endometrial carcinoma. METHODS: Data of 367 patients who diagnosed with endometrial carcinoma at the First Affiliated Hospital of Chongqing Medical University between January 2012 and August 2018 was retrospectively analyzed. The prediction accuracy was evaluated by receiver operating characteristics curves and Youden's J statistics. Hosmer-lemeshow test was used to confirm the goodness of fit of the model. The prognostic value of serum ferritin on disease free survival (DFS) and overall survival (OS) of endometrial carcinoma was evaluated by univariate log-rank tests and multivariate cox regression models. RESULTS: Preoperative high serum ferritin was correlated with older age, high grade, specific histological subtypes and recurrence of endometrial carcinoma (P < 0.05). The DFS and OS of 198 patients with elevated serum ferritin levels were significantly lower than those with low serum ferritin levels (P = 0.001 and P = 0.002, respectively). In multivariate analysis, serum ferritin was an independent prognostic factor for DFS and OS in endometrial carcinoma (P = 0.012, P = 0.028). CONCLUSION: Through our research, we found that the high expression of serum ferritin level was not only related to low DFS and OS in patients with endometrial carcinoma, but also related to the high-risk factors of endometrial carcinoma recurrence. So serum ferritin levels may be used to predict the poor prognosis of patients with endometrial carcinoma.

Assessment of dynamic drought-induced ecosystem risk: Integrating time-varying hazard frequency, exposure and vulnerability.

Terrestrial ecosystems, occupying 28.26% of Earth's surface, are extensively at risk from droughts, which is likely to propagate into human communities owing to loss of vital services. Ecosystem risk also tends to fluctuate within anthropogenically-forced nonstationary environments, raising considerable concerns about effectiveness of mitigation strategies. This study aims to assess dynamic ecosystem risk induced by droughts and identify risk hotspots. Bivariate nonstationary drought frequency was initially derived as a hazard component of risk. By coupling vegetation coverage and biomass quantity, a two-dimensional exposure indicator was developed. Trivariate likelihood of vegetation decline was calculated under arbitrary droughts to intuitively determine ecosystem vulnerability. Ultimately, time-variant drought frequency, exposure and vulnerability were multiplied to derive dynamic ecosystem risk, followed by hotspot and attribution analyses. Risk assessment implemented in the drought-prevalent Pearl River basin (PRB) of China during 1982-2017 showed that meteorological droughts in eastern and western margins, although less frequent, were prolonged and aggravated in contrast to prevalence of less persistent and severe droughts in the middle. In 86.12% of the PRB, ecosystem exposure maintains high levels (0.62). Relatively high vulnerability (>0.5) occurs in water-demanding agroecosystems, exhibiting a northwest-southeast-directed extension. A 0.1-degree risk atlas unveils that high and medium risks occupy 18.96% and 37.99% of the PRB, while risks are magnified in the north. The most pressing hotspots with high risk continuing to escalate reside in the East River and Hongliu River basins. Our results provide knowledge of composition, spatio-temporal variability and driving mechanism of drought-induced ecosystem risk, which will assist in risk-based mitigation prioritization.

Catalytic Furfural/5-Hydroxymethyl Furfural Oxidation to Furoic Acid/Furan-2,5-dicarboxylic Acid with H2 Production Using Alkaline Water as the Formal Oxidant.

Furfural and 5-hydroxymethyl furfural (HMF) are abundantly available biomass-derived renewable chemical feedstocks, and their oxidation to furoic acid and furan-2,5-dicarboxylic acid (FDCA), respectively, is a research area with huge prospective applications in food, cosmetics, optics, and renewable polymer industries. Water-based oxidation of furfural/HMF is a lucrative approach for simultaneous generation of H2 and furoic acid/FDCA. However, this process is currently limited to (photo)electrochemical methods that can be challenging to control, improve, and scale up. Herein, we report well-defined ruthenium pincer catalysts for direct homogeneous oxidation of furfural/HMF to furoic acid/FDCA, using alkaline water as the formal oxidant while producing pure H2 as the reaction byproduct. Mechanistic studies indicate that the ruthenium complex not only catalyzes the aqueous oxidation but also actively suppresses background decomposition by facilitating initial Tishchenko coupling of substrates, which is crucial for reaction selectivity. With further improvement, this process can be used in scaled-up facilities for a simultaneous renewable building block and fuel production.

CC chemokine receptor 2 (CCR2) expression promotes diffuse large B-Cell lymphoma survival and invasion.

In recent years, CC chemokine receptor 2 (CCR2) has been found to be involved in tumor growth, angiogenesis, epithelial mesenchymal transition, metastasis, and immune escape. CCR2 overexpression was first identified as a poor prognostic predictor in diffuse large B-cell lymphoma (DLBCL) in our published article, but the mechanisms involved remain unknown. In this work, we collected data from another 138 patients with DLBCL data and verified the CCR2 expression level and its relationship to clinicopathological characteristics. Furthermore, we explored the possible mechanisms via in vitro and in vivo experiments. We showed that CCR2 overexpression was an independent prognostic marker and predicted shorter overall survival (OS) and progression-free survival (PFS) in patients with DLBCL. Blockade of CCR2 expression with a CCR2 antagonist inhibited tumor cell proliferation, migration, and anti-apoptosis ability in vitro by affecting the PI3K/Akt signaling pathway and the p38 MAPK signaling pathway. Furthermore, administration of a CCR2 antagonist decreased tumor growth and dissemination of DLBCL cells and increased survival time in the xenograft model. Our study demonstrates that CCR2 expression plays an important role in the development of DLBCL by stimulating cell proliferation, migration, and anti-apoptosis. Therefore, the inhibition of CCR2 may be a potential target for anticancer therapy in DLBCL.

Artesunate restores mitochondrial fusion-fission dynamics and alleviates neuronal injury in Alzheimer's disease models.

Alzheimer's disease (AD) remains a leading cause of dementia and no therapy that reverses underlying neurodegeneration is available. Recent studies suggest the protective role of artemisinin, an antimalarial drug, in neurological disorders. In this study, we investigated the therapeutic potential of artesunate, a water-soluble derivative of artemisinin, on amyloid-beta (Aß)-treated challenged microglial BV-2, neuronal N2a cells, and the amyloid precursor protein/presenilin (APP/PS1) mice model. We found that Aß significantly induced multiple AD-related phenotypes, including increased expression/production of pro-inflammatory cytokines from microglial cells, enhanced cellular and mitochondrial production of reactive oxygen species, promoted mitochondrial fission, inhibited mitochondrial fusion, suppressed mitophagy or biogenesis in both cell types, stimulated apoptosis of neuronal cells, and microglia-induced killing of neurons. All these in vitro phenotypes were attenuated by artesunate. In addition, the over-expression of the mitochondrial fission protein Drp-1, or down-regulation of the mitochondrial fusion protein OPA-1 both reduced the therapeutic benefits of artesunate. Artesunate also alleviated AD phenotypes in APP/PS1 mice, reducing Aß deposition, and reversing deficits in memory and learning. Artesunate protects neuronal and microglial cells from AD pathology, both in vitro and in vivo. Maintaining mitochondrial dynamics and simultaneously targeting multiple AD pathogenic mechanisms are associated with the protective effects of artesunate. Consequently, artesunate may become a promising therapeutic for AD.

Retrieving High-Dimensional Quantum Steering from a Noisy Environment with N Measurement Settings.

One of the most often implied benefits of high-dimensional (HD) quantum systems is to lead to stronger forms of correlations, featuring increased robustness to noise. Here, we experimentally demonstrate the n-setting linear HD quantum steering criterion. We verify the large violation of the steering inequalities without full-state tomography. The lower bound of the violation is 2.24±0.01 in 11 dimensions, exceeding the bound (V<2) of two-setting criteria. Hence, a higher strength of steering has been revealed. Moreover, we demonstrate the method for enhancing the noise robustness without increasing dimension, alternatively, by increasing measurement settings. Using the entanglement in 11 dimensions, we experimentally retrieve steering nonlocality with 63.4±1.4% isotropic noise fraction, surpassing the 50% limitation of two-setting criteria. Our Letter offers the potential for practical one-sided device-independent quantum information processing that tolerates the noisy environment, lossy detection, and transcends the present transmission distance limitation.

Immunofluorescent-aggregation assay based on anti-Salmonella typhimurium IgG-AuNCs, for rapid detection of Salmonella typhimurium.

Sensitive and rapid detection of pathogenic bacteria plays an important role in avoiding food poisoning. However, the practical application value of conventional assays for detection of foodborne bacteria, are limited by major drawbacks; these include the laboriousness of pure culture preparation, complexity of DNA extraction for polymerase chain reaction, and low sensitivity of enzyme-linked immunosorbent assay. Herein, we designed a non-complex strategy for the sensitive, quantitative, and rapid detection of Salmonella typhimurium with high specificity, using an anti-Salmonella typhimurium IgG-AuNC-based immunofluorescent-aggregation assay. Salmonella typhimurium was agglutinated with fluorescent anti-Salmonella typhimurium IgG-AuNC on a glass slide, and observed using a fluorescence microscope with photoexcitation and photoemission at 560 nm and 620 nm, respectively. Under optimized reaction conditions, the AuNC-based immunofluorescent-aggregation assay had a determination range between 7.0 × 103 and 3.0 × 108 CFU/mL, a limit of detection of 1.0 × 103 CFU/mL and an assay response time of 3 min. The technique delivered good results in assessing real samples.

Medial Epicanthoplasty With the Classic and Modified Skin Redraping Method: A Retrospective Case Control Study.

ABSTRACT: The skin redraping method for medial epicanthoplasty is characterized by some shortcomings which warrants modification. In this study, clinical data of 193 patients who underwent medial epichanthoplasty by the modified skin redraping technique or the classic skin redraping technique were reviewed retrospectively. The patients underwent operation between May 2018 and June 2020 and were followed up for not less than 6 months. Interepicanthal distance, interpupillary distance, patient satisfaction, and postoperative complications were evaluated. In terms of interepicanthal distance/inter-pupillary distance ratio (P > 0.05) and satisfaction score (P = 0.759), the modified skin redraping technique and the classic skin redraping technique were similar. In the classic skin redraping group, there were 3 cases of visible scarring in the lower eyelid, corresponding to significantly more cases than in the modified skin redraping group (n = 0, P < 0.001). There were more out-fold cases in the modified skin redraping group (76/90) than in the classic skin redraping group (17/88) (P < 0.001). Utilizing the modified skin redraping medial epicanthoplasty can prevent medial hooding of the upper eyelid, reduce the probability of visible scarring, and produce more out-fold with concurrent double eyelidplasty compared with classic skin redraping epicanthoplasty. Level of evidence: IV.

Self-Anti-Stacking 2D Metal Phosphide Loop-Sheet Heterostructures by Edge-Topological Regulation for Highly Efficient Water Oxidation.

2D metal phosphide loop-sheet heterostructures are controllably synthesized by edge-topological regulation, where Ni2 P nanosheets are edge-confined by the N-doped carbon loop, containing ultrafine NiFeP nanocrystals (denoted as NiFeP@NC/Ni2 P). This loop-sheet feature with lifted-edges prevents the stacking of nanosheets and induces accessible open channels for catalytic site exposure and gas bubble release. Importantly, these NiFeP@NC/Ni2 P hybrids exhibit a remarkable oxygen evolution activity with an overpotential of 223 mV at 20 mA cm-2 and a Tafel slope of 46.1 mV dec-1 , constituting the record-high performance among reported metal phosphide electrocatalysts. The NiFeP@NC/Ni2 P hybrids are also employed as both anode and cathode to achieve an alkaline electrolyzer for overall water splitting, delivering a current density of 10 mA cm-2 with a voltage of 1.57 V, comparable to that of the commercial Pt/C||RuO2 couple (1.56 V). Moreover, a photovoltaic-electrolysis coupling system can as well be effectively established for robust overall water splitting. Evidently, this ingenious protocol would expand the toolbox for designing efficient 2D nanomaterials for practical applications.

Efficient deletion of multiple circle RNA loci by CRISPR-Cas9 reveals Os06circ02797 as a putative sponge for OsMIR408 in rice.

CRISPR-Cas9 is an emerging genome editing tool for reverse genetics in plants. However, its application for functional study of non-coding RNAs in plants is still at its infancy. Despite being a major class of non-coding RNAs, the biological roles of circle RNAs (circRNAs) remain largely unknown in plants. Previous plant circRNA studies have focused on identification and annotation of putative circRNAs, with their functions largely uninvestigated by genetic approaches. Here, we applied a multiplexed CRISPR-Cas9 strategy to efficiently acquire individual null mutants for four circRNAs in rice. We showed each of these rice circRNA loci (Os02circ25329, Os06circ02797, Os03circ00204 and Os05circ02465) can be deleted at 10% or higher efficiency in both protoplasts and stable transgenic T0 lines. Such high efficiency deletion enabled the generation of circRNA null allele plants without the CRISPR-Cas9 transgene in the T1 generation. Characterization of the mutants reveals these circRNAs' participation in salt stress response during seed germination and in particular the Os05circ02465 null mutant showed high salt tolerance. Notably, the seedlings of the Os06circ02797 mutant showed rapid growth phenotype after seed germination with the seedlings containing higher chlorophyll A/B content. Further molecular and computational analyses suggested a circRNA-miRNA-mRNA regulatory network where Os06circ02797 functions to bind and sequester OsMIR408, an important and conserved microRNA in plants. This study not only presents genetic evidence for the first time in plants that certain circRNAs may serve as sponges to negatively regulate miRNAs, a phenomenon previously demonstrated in mammalian cells, but also provides important insights for improving agronomic traits through gene editing of circRNA loci in crops.

Homogeneous Reforming of Aqueous Ethylene Glycol to Glycolic Acid and Pure Hydrogen Catalyzed by Pincer-Ruthenium Complexes Capable of Metal-Ligand Cooperation.

Glycolic acid is a useful and important α-hydroxy acid that has broad applications. Herein, the homogeneous ruthenium catalyzed reforming of aqueous ethylene glycol to generate glycolic acid as well as pure hydrogen gas, without concomitant CO2 emission, is reported. This approach provides a clean and sustainable direction to glycolic acid and hydrogen, based on inexpensive, readily available, and renewable ethylene glycol using 0.5 mol % of catalyst. In-depth mechanistic experimental and computational studies highlight key aspects of the PNNH-ligand framework involved in this transformation.