Comparison between intramedullary nail and conventional plate for displaced intra-articular calcaneal fractures: A meta-analysis.

OBJECTIVES: This study aimed to compare the efficacy and safety of the intramedullary nail and conventional plate for the treatment of displaced intra-articular calcaneal fractures from clinical comparative trials. MATERIALS AND METHODS: A comprehensive search of English databases was carried out in the Springer, PubMed, ScienceDirect, Web of Science, and Cochrane Library databases until September 2023. Studies on calcaneal fractures treated by an intramedullary nail or a plate were considered for inclusion. Endpoints included duration of operation, length of hospital stay, the Visual Analog Scale (VAS) score, postoperative functional score, radiological parameters, and complications. The mean difference (MD) and risk difference (RD) as the combined variables, as well as the 95% confidence intervals, (CIs) were calculated. RESULTS: Five retrospective controlled studies covering 473 feet at the one-year follow-up met the inclusion criteria. The meta-analysis demonstrated that there were significant differences in the duration of operation (MD: -10.81; 95% CI: -16.32, -5.31; p=0.0001), length of hospital stay (MD: -3.65; 95% CI: -4.35, -2.95; p<0.00001). No significant differences were found regarding postoperative American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale (MD: 0.36; 95% CI: -3.89, 4.61; p=0.87), VAS (MD: 1.95; 95% CI: -0.30, 4.21; p=0.09), or postoperative Böhler angle (MD: 0.94; 95% CI: -0.04, 1.92; p=0.06) between the two groups. The incidence of total complications (RD: -0.31; 95% CI: -0.46, -0.17; p<0.0001) and wound-healing complications (RD: -0.16; 95% CI: -0.30, -0.03; p=0.02) were lower in the intramedullary nail group. There were no significant differences in the incidences of revision surgery, implant removal, superficial wound infection, deep infection, and nonunion. CONCLUSION: Compared to conventional plates, the intramedullary nail showed a shorter duration of operation, reduced length of hospital stay, and fewer postoperative total complications and wound-healing complications in treating displaced intra-articular calcaneal fractures.

Anthropogenic and biological activities elevate microplastics pollution in headwater ecosystem of Yangtze tributaries in Hindu Kush-Himalayan region.

Microplastic (MP) pollution is widely spread in oceans, freshwater, and terrestrial environments but MPs in mountainous headwater ecosystem are rarely reported. This study focuses on the headwater of Yangtze tributaries of the Hindu Kush-Himalayan (HKH) region. Five streams at elevations of 900 to 3300 m were selected to investigate the distribution of MPs in water and sediments across altitudes. MPs were found in all water and sediment samples from top stream zone nearly in absence of anthropogenic activity, low anthropogenic zone, and high anthropogenic zone, increased from 12-54, 81-185 to 334-847 items/L, and 2-35, 26-84 to 124-428 items/kg, respectively. This elevation-dependent MP distribution indicated that as elevation decreased, anthropogenic activities intensified and increased MPs input and their abundance, size, and diversity. Notably, hydraulic projects, such as damming, were identified as potential barriers to the migration of MPs downstream. Microbiome analyses revealed the presence of bacterial genes associated with plastic biodegradation in all sediment samples. The study indicates that Shangri-la mountainous streams have been polluted with MPs for years with potential risk of generation of nano-sized particles via natural fragmentation and biodegradation, and thus raises concern on MPs pollution in headwaters streams in mountainous regions.

Unveiling the impact of cryptic plasmids curing on Escherichia coli Nissle 1917: massive increase in Ag43c expression.

Escherichia coli Nissle 1917 (EcN) is an important chassis strain widely used for the development of live biotherapeutic products (LBPs). EcN strain naturally harbors two cryptic plasmids with unknown function. During the development of LBPs using EcN strain, the cryptic plasmids were cured usually to avoid plasmid incompatibility or alleviate metabolic burdens associated with these cryptic plasmids. While the cryptic plasmids curing in EcN may appear to be a routine procedure, the comprehensive impact of cryptic plasmids curing on the EcN strain remains incompletely understood. In the present study, the effects of cryptic plasmids curing on EcN were investigated using transcriptome sequencing. The results revealed that only a small number of genes showed significant changes in mRNA levels after cryptic plasmid curing (4 upregulated and 6 downregulated genes), primarily involved in amino acid metabolism. Furthermore, the flu gene showed the most significant different expression, encoding Antigen 43 (Ag43) protein, a Cah family adhesin. Mass spectrometry analysis further confirmed the significant increase in Ag43 expression. Ag43 is commonly present in Escherichia coli and mediates the bacterial autoaggregation. However, despite the upregulation of Ag43 expression, no Ag43-mediated cell self-sedimentation was observed in the cured EcN strain. These findings contribute to making informed decisions regarding the curing of the cryptic plasmids when Escherichia coli Nissle 1917 is used as the chassis strain.

Viral infection and spread are inhibited by the polyubiquitination and downregulation of TRPV2 channel by the interferon-stimulated gene TRIM21.

Interferon (IFN) contributes to the host's antiviral response by inducing IFN-stimulated genes (ISGs). However, their functional targets and the mechanism of action remain elusive. Here, we report that one such ISG, TRIM21, interacts with and degrades the TRPV2 channel in myeloid cells, reducing its expression and providing host protection against viral infections. Moreover, viral infection upregulates TRIM21 in paracrine and autocrine manners, downregulating TRPV2 in neighboring cells to prevent viral spread to uninfected cells. Consistently, the Trim21-/- mice are more susceptible to HSV-1 and VSV infection than the Trim21+/+ littermates, in which viral susceptibility is rescued by inhibition or deletion of TRPV2. Mechanistically, TRIM21 catalyzes the K48-linked ubiquitination of TRPV2 at Lys295. TRPV2K295R is resistant to viral-infection-induced TRIM21-dependent ubiquitination and degradation, promoting viral infection more profoundly than wild-type TRPV2 when reconstituted into Lyz2-Cre;Trpv2fl/fl myeloid cells. These findings characterize targeting the TRIM21-TRPV2 axis as a conducive strategy to control viral spread to bystander cells.

Expression of USP25 associates with fibrosis, inflammation and metabolism changes in IgG4-related disease.

IgG4-related disease (IgG4-RD) has complex clinical manifestations ranging from fibrosis and inflammation to deregulated metabolism. The molecular mechanisms underpinning these phenotypes are unclear. In this study, by using IgG4-RD patient peripheral blood mononuclear cells (PBMCs), IgG4-RD cell lines and Usp25 knockout mice, we show that ubiquitin-specific protease 25 (USP25) engages in multiple pathways to regulate fibrotic and inflammatory pathways that are characteristic to IgG4-RD. Reduced USP25 expression in IgG4-RD leads to increased SMAD3 activation, which contributes to fibrosis and induces inflammation through the IL-1ß inflammatory axis. Mechanistically, USP25 prevents ubiquitination of RAC1, thus, downregulation of USP25 leads to ubiquitination and degradation of RAC1. Decreased RAC1 levels result in reduced aldolase A release from the actin cytoskeleton, which then lowers glycolysis. The expression of LYN, a component of the B cell receptor signalosome is also reduced in USP25-deficient B cells, which might result in B cell activation deficiency. Altogether, our results indicate a potential anti-inflammatory and anti-fibrotic role for USP25 and make USP25 a promising diagnostic marker and potential therapeutic target in IgG4-RD.

Non-negligible impact of microplastics on wetland ecosystems.

There has been much concern about microplastic (MP) pollution in marine and soil environments, but attention is gradually shifting towards wetland ecosystems, which are a transitional zone between aquatic and terrestrial ecosystems. This paper comprehensively reviews the sources of MPs in wetland ecosystems, as well as their occurrence characteristics, factors influencing their migration, and their effects on animals, plants, microorganisms, and greenhouse gas (GHG) emissions. It was found that MPs in wetland ecosystems originate mainly from anthropogenic sources (sewage discharge, and agricultural and industrial production) and natural sources (rainfall-runoff, atmospheric deposition, and tidal effects). The most common types and forms of MPs identified in the literature were polyethylene and polypropylene, fibers, and fragments. The migration of MPs in wetlands is influenced by both non-biological factors (the physicochemical properties of MPs, sediment characteristics, and hydrodynamic conditions) and biological factors (the adsorption and growth interception by plant roots, ingestion, and animal excretion). Furthermore, once MPs enter wetland ecosystems, they can impact the resident microorganisms, animals, and plants. They also have a role in global warming because MPs act as unique exogenous carbon sources, and can also influence GHG emissions in wetland ecosystems by affecting the microbial community structure in wetland sediments and abundance of genes associated with GHG emissions. However, further investigation is needed into the influence of MP type, size, and concentration on the GHG emissions in wetlands and the underlying mechanisms. Overall, the accumulation of MPs in wetland ecosystems can have far-reaching consequences for the local ecosystem, human health, and global climate regulation. Understanding the effects of MPs on wetland ecosystems is essential for developing effective management and mitigation strategies to safeguard these valuable and vulnerable environments.

The CDK4/6 Inhibitor Palbociclib Induces Cell Senescence of High-grade Serous Ovarian Cancer Through Acetylation of p53.

Cell senescence is an anti-cancer strategy following DNA repair and apoptosis, which is associated with the initiation, progression, and treatment of ovarian cancer. The CDK4/6 inhibitor alters cell cycle and induces cell senescence dependent on retinoblastoma (RB) family proteins. Objective Herein, we aimed to explore the effects of Palbociclib (a CDK4/6 inhibitor) on cellular senescence of high-grade serous ovarian cancer (HGSOC). Cell viability and cell cycle were evaluated by cell counting kit-8 and flow cytometry. Cell senescence was analyzed using the SA-ß-gal staining assay. The senescence-associated secretory phenotype was assessed using quantitative PCR (qPCR). Senescence-related markers were tested using western blot. The role of Palbociclib in vivo was clarified using xenograft tumor. Acetylation of p53 was evaluated by qPCR and western blot. The results showed that Palbociclib inhibited cell viability, blocked cell cycle at G0/G1 phase, and induced cell senescence. A rescue study indicated that knockdown of p53 reversed the effects on cell cycle and senescence induced by Palbociclib. Moreover, we found that Palbociclib promotes P300-mediated p53 acetylation, thus increasing p53 stability and transcription activity. Moreover, Palbociclib suppressed tumor growth in vivo with increased p53 and acetylated p53 levels. In conclusion, Palbociclib induced cell senescence of HGSOC through P300-mediated p53 acetylation, suggesting that Palbociclib may have the effect of treating HGSOC.

Disulfiram ameliorates STING/MITA-dependent inflammation and autoimmunity by targeting RNF115.

STING (also known as MITA) is an adaptor protein that mediates cytoplasmic DNA-triggered signaling, and aberrant activation of STING/MITA by cytosolic self-DNA or gain-of-function mutations causes severe inflammation. Here, we show that STING-mediated inflammation and autoimmunity are promoted by RNF115 and alleviated by the RNF115 inhibitor disulfiram (DSF). Knockout of RNF115 or treatment with DSF significantly inhibit systemic inflammation and autoimmune lethality and restore immune cell development in Trex1-/- mice and STINGN153S/WT bone marrow chimeric mice. In addition, knockdown or pharmacological inhibition of RNF115 substantially downregulate the expression of IFN-α, IFN-γ and proinflammatory cytokines in PBMCs from patients with systemic lupus erythematosus (SLE) who exhibit high concentrations of dsDNA in peripheral blood. Mechanistically, knockout or inhibition of RNF115 impair the oligomerization and Golgi localization of STING in various types of cells transfected with cGAMP and in organs and cells from Trex1-/- mice. Interestingly, knockout of RNF115 inhibits the activation and Golgi localization of STINGN153S as well as the expression of proinflammatory cytokines in myeloid cells but not in endothelial cells or fibroblasts. Taken together, these findings highlight the RNF115-mediated cell type-specific regulation of STING and STINGN153S and provide potential targeted intervention strategies for STING-related autoimmune diseases.

In vitro and in vivo Biological Evaluation of Newly Tacrine-Selegiline Hybrids as Multi-Target Inhibitors of Cholinesterases and Monoamine Oxidases for Alzheimer's Disease.

Purpose: Alzheimer's disease (AD) is the most common neurodegenerative disease, and its multifactorial nature increases the difficulty of medical research. To explore an effective treatment for AD, a series of novel tacrine-selegiline hybrids with ChEs and MAOs inhibitory activities were designed and synthesized as multifunctional drugs. Methods: All designed compounds were evaluated in vitro for their inhibition of cholinesterases (AChE/BuChE) and monoamine oxidases (MAO-A/B) along with their blood-brain barrier permeability. Then, further biological activities of the optimizing compound 7d were determined, including molecular model analysis, in vitro cytotoxicity, acute toxicity studies in vivo, and pharmacokinetic and pharmacodynamic property studies in vivo. Results: Most synthesized compounds demonstrated potent inhibitory activity against ChEs/MAOs. Particularly, compound 7d exhibited good and well-balanced activity against ChEs (hAChE: IC50 = 1.57 µM, hBuChE: IC50 = 0.43 µM) and MAOs (hMAO-A: IC50 = 2.30 µM, hMAO-B: IC50 = 4.75 µM). Molecular modeling analysis demonstrated that 7d could interact simultaneously with both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE in a mixed-type manner and also exhibits binding affinity towards BuChE and MAO-B. Additionally, 7d displayed excellent permeability of the blood-brain barrier, and under the experimental conditions, it elicited low or no toxicity toward PC12 and BV-2 cells. Furthermore, 7d was not acutely toxic in mice at doses up to 2500 mg/kg and could improve the cognitive function of mice with scopolamine-induced memory impairment. Lastly, 7d possessed well pharmacokinetic characteristics. Conclusion: In light of these results, it is clear that 7d could potentially serve as a promising multi-functional drug for the treatment of AD.

Tracking Regulatory Mechanism of Trace Fe on Graphene Electromagnetic Wave Absorption.

Polarization and conductance losses are the fundamental dielectric attenuation mechanisms for graphene-based absorbers, but it is not fully understood in revealing the loss mechanism of affect graphene itself. For the first time, the reduced graphene oxide (RGO) based absorbers are developed with regulatory absorption properties and the absorption mechanism of RGO is mainly originated from the carrier injection behavior of trace metal Fe nanosheets on graphene. Accordingly, the minimum reflection loss (RLmin) of Fe/RGO-2 composite reaches - 53.38 dB (2.45 mm), and the effective absorption bandwidth achieves 7.52 GHz (2.62 mm) with lower filling loading of 2 wt%. Using off-axis electron hologram testing combined with simulation calculation and carrier transport property experiments, we demonstrate here the carrier injection behavior from Fe to graphene at the interface and the induced charge accumulation and rearrangement, resulting in the increased interfacial and dipole polarization and the conductance loss. This work has confirmed that regulating the dielectric property of graphene itself by adding trace metals can not only ensure good impedance matching, but also fully exploit the dielectric loss ability of graphene at low filler content, which opens up an efficient way for designing lightweight absorbers and may be extended to other types materials.

Non-canonical regulation of the reactivation of an oncogenic herpesvirus by the OTUD4-USP7 deubiquitinases.

Deubiquitinases (DUBs) remove ubiquitin from substrates and play crucial roles in diverse biological processes. However, our understanding of deubiquitination in viral replication remains limited. Employing an oncogenic human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) to probe the role of protein deubiquitination, we found that Ovarian tumor family deubiquitinase 4 (OTUD4) promotes KSHV reactivation. OTUD4 interacts with the replication and transcription activator (K-RTA), a key transcription factor that controls KSHV reactivation, and enhances K-RTA stability by promoting its deubiquitination. Notably, the DUB activity of OTUD4 is not required for K-RTA stabilization; instead, OTUD4 functions as an adaptor protein to recruit another DUB, USP7, to deubiquitinate K-RTA and facilitate KSHV lytic reactivation. Our study has revealed a novel mechanism whereby KSHV hijacks OTUD4-USP7 deubiquitinases to promote lytic reactivation, which could be potentially harnessed for the development of new antiviral therapies.

Cysteine and glycine-rich protein 2 retards platelet-derived growth factor-BB-evoked phenotypic transition of airway smooth muscle cells by decreasing YAP/TAZ activity.

Cysteine and glycine-rich protein 2 (Csrp2) has emerged as a key factor in controlling the phenotypic modulation of smooth muscle cells. The phenotypic transition of airway smooth muscle cells (ASMCs) is a pivotal step in developing airway remodeling during the onset of asthma. However, whether Csrp2 mediates the phenotypic transition of ASMCs in airway remodeling during asthma onset is undetermined. This work aimed to address the link between Csrp2 and the phenotypic transition of ASMCs evoked by platelet-derived growth factor (PDGF)-BB in vitro. The overexpression or silencing of Csrp2 in ASMCs was achieved through adenovirus-mediated gene transfer. The expression of mRNA was measured by quantitative real-time-PCR. Protein levels were determined through Western blot analysis. Cell proliferation was detected by EdU assay and Calcein AM assays. Cell cycle distribution was assessed via fluorescence-activated cell sorting assay. Cell migration was evaluated using the scratch-wound assay. The transcriptional activity of Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) was measured using the luciferase reporter assay. A decline in Csrp2 level occurred in PDGF-BB-stimulated ASMCs. Increasing Csrp2 expression repressed the PDGF-BB-evoked proliferation and migration of ASMCs. Moreover, increasing Csrp2 expression impeded the phenotypic change of PDGF-BB-stimulated ASMCs from a contractile phenotype into a synthetic/proliferative phenotype. On the contrary, the opposite effects were observed in Csrp2-silenced ASMCs. The activity of YAP/TAZ was elevated in PDGF-BB-stimulated ASMCs, which was weakened by Csrp2 overexpression or enhanced by Csrp2 silencing. The YAP/TAZ activator could reverse Csrp2-overexpression-mediated suppression of the PDGF-BB-evoked phenotypic switching of ASMCs, while the YAP/TAZ suppressor could dimmish Csrp2-silencing-mediated enhancement on PDGF-BB-evoked phenotypic switching of ASMCs. In summary, Csrp2 serves as a determinant for the phenotypic switching of ASMCs. Increasing Csrp2 is able to impede PDGF-BB-evoked phenotypic change of ASMCs from a synthetic phenotype into a synthetic/proliferative phenotype through the effects on YAP/TAZ. This work implies that Csrp2 may be a key player in airway remodeling during the onset of asthma.

USP2 inhibition prevents infection with ACE2-dependent coronaviruses in vitro and is protective against SARS-CoV-2 in mice.

Targeting angiotensin-converting enzyme 2 (ACE2) represents a promising and effective approach to combat not only the COVID-19 pandemic but also potential future pandemics arising from coronaviruses that depend on ACE2 for infection. Here, we report ubiquitin specific peptidase 2 (USP2) as a host-directed antiviral target; we further describe the development of MS102, an orally available USP2 inhibitor with viable antiviral activity against ACE2-dependent coronaviruses. Mechanistically, USP2 serves as a physiological deubiquitinase of ACE2, and targeted inhibition with specific small-molecule inhibitor ML364 leads to a marked and reversible reduction in ACE2 protein abundance, thereby blocking various ACE2-dependent coronaviruses tested. Using human ACE2 transgenic mouse models, we further demonstrate that ML364 efficiently controls disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as evidenced by reduced viral loads and ameliorated lung inflammation. Furthermore, we improved the in vivo performance of ML364 in terms of both pharmacokinetics and antiviral activity. The resulting lead compound, MS102, holds promise as an oral therapeutic option for treating infections with coronaviruses that are reliant on ACE2.

PD-1 signaling negatively regulates the common cytokine receptor γ chain via MARCH5-mediated ubiquitination and degradation to suppress anti-tumor immunity.

Combination therapy with PD-1 blockade and IL-2 substantially improves anti-tumor efficacy comparing to monotherapy. The underlying mechanisms responsible for the synergistic effects of the combination therapy remain enigmatic. Here we show that PD-1 ligation results in BATF-dependent transcriptional induction of the membrane-associated E3 ubiquitin ligase MARCH5, which mediates K27-linked polyubiquitination and lysosomal degradation of the common cytokine receptor γ chain (γc). PD-1 ligation also activates SHP2, which dephosphorylates γcY357, leading to impairment of γc family cytokine-triggered signaling. Conversely, PD-1 blockade restores γc level and activity, thereby sensitizing CD8+ T cells to IL-2. We also identified Pitavastatin Calcium as an inhibitor of MARCH5, which combined with PD-1 blockade and IL-2 significantly improves the efficacy of anti-tumor immunotherapy in mice. Our findings uncover the mechanisms by which PD-1 signaling antagonizes γc family cytokine-triggered immune activation and demonstrate that the underlying mechanisms can be exploited for increased efficacy of combination immunotherapy of cancer.

Integrated vegetation cover of typical steppe in China based on mixed decomposing derived from high resolution remote sensing data.

Grasslands represent the largest ecosystem in China, accurate and efficient extraction of its integrated vegetation cover (IVC) plays a crucial role in supporting policy decisions. This study presented a method for grassland monitoring via IVC derived from high-resolution satellite data. Taking the multispectral data of Gaofen-1 (GF-1) and Gaofen-6 (GF-6) with 16 m resolution as the main data source, vegetation cover of six representative regions was assessed based on mixed-pixel decomposition model. Using grassland vegetation cover and ratio of grassland area, the IVC in each site was calculated and verified against ground-measured sample data. The results showed that the IVC of grassland was closely related to vegetation habitat driven by regional hydrothermal regime. Yichang grassland, dominated with warm-temperate shrub tussock type, had the highest IVC (80.06 %) due to its favorable hydrothermal conditions. For the main grassland types in Hulunbuir and Gansu Province (temperate meadow steppe and temperate typical steppe), the IVC was 79.38 % and 58.46 %, respectively. In both Xilin-Gol and Nagqu, vegetation cover decreased gradually from east to west, and the IVC was merely 42.83 % and 42.61 %, respectively. Both regions are endowed with less hydrothermal resources to different degrees. Alxa, with a predominately temperate desert landscape, had the lowest IVC of 15.58 % where precipitation is extremely scarce. Based on the grass species of measured samples, the dominant species and biodiversity of different grassland types in Gansu Province and Hulunbuir Municipality of Inner Mongolia Autonomous Region were analyzed. The results showed that the meadow grassland has the richest biodiversity. The temperate mountain meadows in Gansu Province have a high species diversity, with a total of 90 grass species, and the lowland meadows in Hulunbuir have a total of 49 grass species. This study utilizes high-resolution data to conduct large-scale vegetation monitoring, which is a viable alternative for efficient assessment of steppe ecology.

Assessment of Land Cover Status and Change in the World and "the Belt and Road" Region from 2016 to 2020.

The assessment of land cover and changes will help to understand the temporal and spatial pattern of land cover in the world and the Belt and Road (B&R) region, and provide reference information for global sustainable development and the Belt and Road construction. In this paper, the 1 km global land cover classification maps of 2016 and 2020 with a high accuracy of 88% are mapped using the Moderate Resolution Imaging Spectroradiometer (MODIS) time series surface reflectance products. Based on the maps, the land cover status of the world and the Belt and Road region, the land cover change from 2016 to 2020, and the mutual transformation characteristics between various types, are analyzed. The research results indicate that from 2016 to 2020, the global change rates of cropland, forest, grassland, and impervious surface are 0.25%, 0.22%, 0.08% and 3.41%, respectively. In the Belt and Road region, the change rates of cropland, forest, grassland, and impervious surface are 0.42%, 0.60%, -0.55% and 2.98% respectively. The assessment results will help to clarify the spatial pattern of land cover change in the five years from 2016 to 2020, so as to provide valuable scientific information for the global realization of sustainable development goals and the construction of the B&R.

Process Chain for Ultra-Precision and High-Efficiency Manufacturing of Large-Aperture Silicon Carbide Aspheric Mirrors.

A large-aperture silicon carbide (SiC) aspheric mirror has the advantages of being light weight and having a high specific stiffness, which is the key component of a space optical system. However, SiC has the characteristics of high hardness and multi-component, which makes it difficult to realize efficient, high-precision, and low-defect processing. To solve this problem, a novel process chain combining ultra-precision shaping based on parallel grinding, rapid polishing with central fluid supply, and magnetorheological finishing (MRF) is proposed in this paper. The key technologies include the passivation and life prediction of the wheel in SiC ultra-precision grinding (UPG), the generation and suppression mechanism of pit defects on the SiC surface, deterministic and ultra-smooth polishing by MRF, and compensation interference detection of the high-order aspheric surface by a computer-generated hologram (CGH). The verification experiment was conducted on a Ø460 mm SiC aspheric mirror, whose initial surface shape error was 4.15 µm in peak-to-valley (PV) and a root-mean-square roughness (Rq) of 44.56 nm. After conducting the proposed process chain, a surface error of RMS 7.42 nm and a Rq of 0.33 nm were successfully obtained. Moreover, the whole processing cycle is only about 216 h, which sheds light on the mass production of large-aperture silicon carbide aspheric mirrors.

Facile fabrication of ultra-light N-doped-rGO/g-C3N4 for broadband microwave absorption.

"Thin thickness", "lightweight", "wide absorption bandwidth" and "strong absorption" are the new standards of contemporary science and technology for microwave absorption(MA) material. In this study, N-doped-rGO/g-C3N4 MA material was prepared for the first time by simple heat treatment, which the N atoms were doped into rGO and g-C3N4 was dispersed on the surface of N-doped-rGO, and its density is only 0.035 g/cm3. The impedance matching of the N-doped-rGO/g-C3N4 composite was well adjusted by decreasing the dielectric constant and attenuation constant due to the g-C3N4 semiconductor property and the graphite-like structure. Moreover, the distribution of g-C3N4 among N-doped-rGO sheets can produce more polarization effect and relaxation effect by increasing the lamellar spacing. Furthermore, the polarization loss of N-doped-rGO/g-C3N4 could be increased successfully by doping N atoms and g-C3N4. Ultimately, the MA property of N-doped-rGO/g-C3N4 composite was optimized significantly, with a loading of 5 wt%, the N-doped-rGO/g-C3N4 composite exhibited the RLmin of -49.59 dB and the effective absorption bandwidth could reach 4.56 GHz when the thickness was only 1.6 mm. The "thin thickness", "lightweight", "wide absorption bandwidth" and "strong absorption" of MA material are actually achieved by the N-doped-rGO/g-C3N4.

Perioperative, oncologic, and functional outcomes of robot-assisted partial nephrectomy for special types of renal tumors (hilar, endophytic, or cystic): an evidence-based analysis of comparative outcomes.

Purpose: This study aims to perform a pooled analysis to compare the outcomes of robot-assisted partial nephrectomy (RAPN) between complex tumors (hilar, endophytic, or cystic) and non-complex tumors (nonhilar, exophytic, or solid) and evaluate the effects of renal tumor complexity on outcomes in patients undergoing RAPN. Methods: Four databases were systematically searched, including Science, PubMed, Web of Science, and Cochrane Library, to identify relevant studies published in English up to December 2022. Review Manager 5.4 was used for statistical analyses and calculations. The study was registered with PROSPERO (Registration number: CRD42023394792). Results: In total, 14 comparative trials, including 3758 patients were enrolled. Compared to non-complex tumors, complex tumors were associated with a significantly longer warm ischemia time (WMD 3.67 min, 95% CI 1.78, 5.57; p = 0.0001), more blood loss (WMD 22.84 mL, 95% CI 2.31, 43.37; p = 0.03), and a higher rate of major complications (OR 2.35, 95% CI 1.50, 3.67; p = 0.0002). However, no statistically significant differences were found between the two groups in operative time, length of stay, transfusion rates, conversion to open nephrectomy and radical nephrectomy rates, estimated glomerular filtration rate (eGFR) decline, intraoperative complication, overall complication, positive surgical margins (PSM), local recurrence, and trifecta achievement. Conclusions: RAPN can be a safe and effective procedure for complex tumors (hilar, endophytic, or cystic) and provides comparable functional and oncologic outcomes to non-complex tumors. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=394792, identifier CRD42023394792.

The deubiquitinase OTUD4 inhibits the expression of antimicrobial peptides in Paneth cells to support intestinal inflammation and bacterial infection.

Dysfunction of the intestinal epithelial barrier causes microbial invasion that would lead to inflammation in the gut. Antimicrobial peptides (AMPs) are essential components of the intestinal epithelial barrier, while the regulatory mechanisms of AMPs expression are not fully characterized. Here, we report that the ovarian tumor family deubiquitinase 4 (OTUD4) in Paneth cells restricts the expression of AMPs and thereby promotes experimental colitis and bacterial infection. OTUD4 is upregulated in the inflamed mucosa of ulcerative colitis patients and in the colon of mice treated with dextran sulfate sodium salt (DSS). Knockout of OTUD4 promotes the expression of AMPs in intestinal organoids after stimulation with lipopolysaccharide (LPS) or peptidoglycan (PGN) and in the intestinal epithelial cells (IECs) of mice after DSS treatment or Salmonella typhimurium (S.t.) infection. Consistently, Vil-Cre;Otud4fl/fl mice and Def-Cre;Otud4fl/fl mice exhibit hyper-resistance to DSS-induced colitis and S.t. infection compared to Otud4fl/fl mice. Mechanistically, knockout of OTUD4 results in hyper K63-linked ubiquitination of MyD88 and increases the activation of NF-κB and MAPKs to promote the expression of AMPs. These findings collectively highlight an indispensable role of OTUD4 in Paneth cells to modulate AMPs production and indicate OTUD4 as a potential target for gastrointestinal inflammation and bacterial infection.