Endoplasmic reticulum stress and therapeutic strategies in metabolic, neurodegenerative diseases and cancer.

The accumulation of unfolded or misfolded proteins within the endoplasmic reticulum (ER), due to genetic determinants and extrinsic environmental factors, leads to endoplasmic reticulum stress (ER stress). As ER stress ensues, the unfolded protein response (UPR), comprising three signaling pathways-inositol-requiring enzyme 1, protein kinase R-like endoplasmic reticulum kinase, and activating transcription factor 6 promptly activates to enhance the ER's protein-folding capacity and restore ER homeostasis. However, prolonged ER stress levels propels the UPR towards cellular demise and the subsequent inflammatory cascade, contributing to the development of human diseases, including cancer, neurodegenerative disorders, and diabetes. Notably, increased expression of all three UPR signaling pathways has been observed in these pathologies, and reduction in signaling molecule expression correlates with decreased proliferation of disease-associated target cells. Consequently, therapeutic strategies targeting ER stress-related interventions have attracted significant research interest. In this review, we elucidate the critical role of ER stress in cancer, metabolic, and neurodegenerative diseases, offering novel therapeutic approaches for these conditions.

Assembly processes of rhizosphere and phyllosphere bacterial communities in constructed wetlands created via transformation of rice paddies.

Constructed wetlands are an efficient and cost-effective method of restoring degraded wetlands, in which the microorganisms present make a significant contribution to the ecosystem. In this study, we comprehensively investigated the patterns of diversity and assembly processes of 7 types of constructed wetlands at the rhizosphere and phyllosphere levels. The results showed that the rhizosphere communities of the constructed wetlands exhibited a more balanced structure than that of paddy fields, and 5 types of constructed wetland demonstrated higher potential diversity than that of paddy fields. However, the opposite trend was observed for the phyllosphere communities. Analysis of mean nearest taxon difference indicated that both deterministic and stochastic processes affected the establishment of the rhizosphere and phyllosphere communities, and stochastic processes may have had a larger effect. An iCAMP model showed that dispersal limitation was the most important factor (67% relative contribution) in the rhizosphere community, while drift was the most important (47% relative contribution) in the phyllosphere community. Mantel tests suggested that sucrase, average height, top height, total biomass, belowground biomass, maximum water-holding capacity, and capillary porosity were significantly correlated with processes in the rhizosphere community, whereas factors such as the deterministic process, average height, top height, and SOC were significantly correlated with deterministic processes in the phyllosphere community. Our results can assist in the evaluation of artificial restorations, and can provide understanding of the ecological processes of microbial communities, as well as new insights into the manipulation of microorganisms in polluted wetland ecosystems.

Bladder-sparing treatment using tislelizumab combined with gemcitabine/cisplatin in selected patients with muscle-invasive bladder cancer: a real-world study.

PURPOSE: To retrospectively evaluate the tislelizumab-based chemoimmunotherapy combined with gemcitabine/cisplatin for bladder-sparing in patients with muscle-invasive bladder cancer (MIBC). METHODS: Forty-five patients who received bladder-sparing treatment or radical cystectomy (RC) for MIBC (cT2-T4a, NxM0) were retrospectively enrolled. All patients received maximal transurethral resection of bladder tumor (mTURBT), followed by four cycles of chemo-immunotherapy with tislelizumab (PD-L1 inhibitor), gemcitabine, and cisplatin. Clinical efficacy was evaluated to compare the benefit of bladder-sparing treatment on clinical CR (cCR) and RC for non-cCR patients. The primary outcomes were bladder intact disease-free survival (BIDFS) and overall survival (OS), and the secondary outcomes were adverse effects. The PD-L1 status and molecular subtypes of tumors were analyzed. RESULTS: The overall survival rate was 88.8% (95%CI: 79.6%, 98.0%) at 12 months, 85.7% (95%CI: 74.9%, 96.5%) at 18 months, and 66.6% (95%CI: 45.2%, 88.0%) at 24 months. Twenty-nine patients (64.4%) achieved cCR and their OS rate was 96.6% (95%CI: 89.9%, 100%). Sixteen patients were in the non-cCR group, and their OS rate was 75.0% (95%CI: 53.8%, 96.2%) at 12 months, 65.6% (95%CI: 40.3%, 90.9%) at 18 months, and 52.5% (95%CI: 21.9%, 83.1%) at 24 months. The BIDFS rate for patients who received bladder-sparing treatment was 96.0% (95%CI: 88.4%, 100%) from 12 to 24 months. Four patients (8.8%) were PD-L1 positive and 41 patients (91.2%) were PD-L1 negative. CONCLUSIONS: Our retrospective study of patients with MIBC suggests that tislelizumab-based neoadjuvant therapy was a safe and effective bladder-sparing treatment.

Functional metal-phenolic cortical cytoskeleton for artificial cells.

Cortex-like cytoskeleton, a thin layer of cross-linked cytoplasmic proteins underlying the cell membrane, plays an essential role in modulating membrane behavior and cell surface properties. However, bottom-up construction of functional cortex-like cytoskeleton in artificial cells remains a challenge. Here, we present metal-phenolic networks as artificial cortical cytoskeletons in liposome-based artificial cells. The metal-phenolic cytoskeleton-reinforced artificial cells exhibit long-term stability, enhanced resistance to a variety of harsh environments, tunable permeability, and well-controlled morphologies. We anticipate that our stable artificial cell models will stride forward to practical applications of liposome-based microsystem.

Genomic Landscape of Lynch Syndrome Colorectal Neoplasia Identifies Shared Mutated Neoantigens for Immunoprevention.

BACKGROUND & AIMS: Lynch syndrome (LS) carriers develop mismatch repair-deficient neoplasia with high neoantigen (neoAg) rates. No detailed information on targetable neoAgs from LS precancers exists, which is crucial for vaccine development and immune-interception strategies. We report a focused somatic mutation and frameshift-neoAg landscape of microsatellite loci from colorectal polyps without malignant potential (PWOMP), precancers, and early-stage cancers in LS carriers. METHODS: We generated paired whole-exome and transcriptomic sequencing data from 8 colorectal PWOMP, 41 precancers, 8 advanced precancers, and 12 early-stage cancers of 43 LS carriers. A computational pipeline was developed to predict, rank, and prioritize the top 100 detected mutated neoAgs that were validated in vitro using ELISpot and tetramer assays. RESULTS: Mutation calling revealed >10 mut/Mb in 83% of cancers, 63% of advanced precancers, and 20% of precancers. Cancers displayed an average of 616 MHC-I neoAgs/sample, 294 in advanced precancers, and 107 in precancers. No neoAgs were detected in PWOMP. A total of 65% of our top 100 predicted neoAgs were immunogenic in vitro, and were present in 92% of cancers, 50% of advanced precancers, and 29% of precancers. We observed increased levels of naïve CD8+ and memory CD4+ T cells in mismatch repair-deficient cancers and precancers via transcriptomics analysis. CONCLUSIONS: Shared frameshift-neoAgs are generated within unstable microsatellite loci at initial stages of LS carcinogenesis and can induce T-cell responses, generating opportunities for vaccine development, targeting LS precancers and early-stage cancers.

Molecular mechanism of the NOS/NOX regulation of antibacterial activity in Eriocheir sinensis.

To elucidate the role of nitric oxide synthase (NOS), which produces the free radical nitric oxide (NO), and nicotinamide adenine dinucleotide phosphate oxidase (NOX), which produces the superoxide anion (O2-), in the innate immunity of Eriocheir sinensis, the full lengths of the NOS and NOX genes were cloned via rapid amplification of the cDNA ends and then expressed in the prokaryotic form to obtain the recombinant proteins, NOS-HIS and NOX-HIS. Through bacterial binding and stimulation experiments, the molecular mechanisms of NOS and NOX in the innate immunity of E. sinensis were explored. Based on the results, NOS and NOX were 5900 bp and 4504 bp long, respectively, and were evolutionarily conserved. Quantitative real-time PCR revealed that NOS and NOX were expressed in all studied tissues, and both were expressed in the highest amounts in hemocytes. NOS-HIS and NOX-HIS could bind to bacteria with different binding powers; their binding ability to gram-positive bacteria was higher than that of binding to gram-negative bacteria. After stimulation with Aeromonas hydrophila, NOS expression was significantly up-regulated at 3, 6, and 48 h, and NOX expression was significantly down-regulated at 3, 12, 24, and 48 h. After bacterial stimulation, the NOS enzyme activity in the serum of E. sinensis was also significantly up-regulated at 6 and 48 h, and the NOX enzyme activity was significantly down-regulated at 12 and 48 h, aligning with the gene expression trend. Moreover, the related free radical molecules, NO, O2-, and H2O2, tended to decrease after bacterial stimulation. Overall, the gene expression and enzyme activity of NOS and NOX had been changed respectively, and the contents of a series of free radical molecules (NO, O2- and H2O2) were induced in E. sinensis after bacterial stimulation, which then exert antibacterial immunity.

Assessing Mailuoning injection in wound healing and thrombophlebitis management: A rat model study.

Thrombophlebitis is the inflammatory condition characterized by obstruction of one or more vessels, commonly in the legs, due to the formation of blood clots. It has been reported that traditional Chinese medicine, including Mailuoning injection, is advantageous for treating inflammatory and blood disorders. This research assessed the therapeutic efficacy of Mailuoning injection in the treatment of thrombophlebitis in rodents, as well as investigated its impact on fibrinolysis, inflammation, and coagulation. An experimental setup for thrombophlebitis was established in rodents via modified ligation technique. Five groups comprised the animals: sham operation group, model group, and three Mailuoning treatment groups (low, medium, and high dosages). The pain response, edema, coagulation parameters (PT, APTT, TT, FIB), serum inflammatory markers (IL-6, TNF-α, CRP), and expression levels of endothelial markers (ICAM-1, VCAM-1, NF-κB) were evaluated. Blood flow and vascular function were further assessed by measuring hemorheological parameters and the concentrations of TXB2, ET, and 6-k-PGF1α. In contrast to the sham group, model group demonstrated statistically significant increases in endothelial expression levels, coagulation latencies, and inflammatory markers (p < 0.05). The administration of mailing, specifically at high and medium dosages, resulted in a substantial reduction in inflammatory markers, enhancement of coagulation parameters, suppression of ICAM-1 and VCAM-1 expression, and restoration of hemorheological measurements to baseline (p < 0.05). Significantly higher concentrations of 6-k-PGF1α and lower levels of TXB2 and ET were observed in high-dose group, suggesting that pro- and anti-thrombotic factors were restored to equilibrium. Utilization of Mailuoning injection in rat model of thrombophlebitis exhibited significant therapeutic impact. This effect was manifested through pain alleviation, diminished inflammation, enhanced blood viscosity and facilitation of fibrinolysis. The study indicated that Mailuoning injection may serve as a viable therapeutic option for thrombophlebitis, potentially aiding in the improvement of wound healing by virtue of its anti-inflammatory and blood flow-enhancing characteristics.

API5-Hsp20 axis regulate apoptosis and viral infection in mud crab (Scylla paramamosain).

Apoptosis Inhibitor 5 (API5) is a widely concerned nuclear protein with diverse functions in organisms, so far, study of API5 is still quite limited in lower animals, and its role in viral immune response has not been addressed. Here, we explored the function of API5 in mud crab (Scylla paramamosain) during White Spot Syndrome Virus (WSSV) infection. The interacting protein Hsp20 of API5 was screened by pull-down assay, and API5 and hsp20 were knocked down by RNAi interference. The results showed that API5 was upregulated along with virus infection, silencing of API5 led to increased WSSV copy numbers and apoptotic rate of hemocytes, highlighting its significance in the immune response. Moreover, we discovered a novel interaction between API5 and Heat Shock Protein 20 (Hsp20), and then revealed that Hsp20 could promote cell apoptosis of hemocytes and reduce viral copy numbers by suppressing API5. The current study therefore improves the knowledge of API5-Hsp20 axis and provides novel insights into intricate mechanisms governing the antiviral response in marine crustaceans.

Understory vegetation diversity patterns of Platycladus orientalis and Pinus elliottii communities in Central and Southern China.

As a vital component of arbor forests, understory vegetation serves as an essential buffer zone for storing carbon due to its strong capacity for community regeneration. This study aimed to identify the diversity pattern and construction mechanism of Platycladus orientalis and Pinus elliottii understory vegetation based on large-scale sample surveys. The Bayesian Information Criterion value of species abundance distribution (SAD) indicated that the Zipf and Zipf-Mandelbrot models were the best-fitting models. The SAD and gambin fitting results suggested that the Pi. elliottii community had a more balanced structure, with most species being relatively abundant. The multiple regression tree model detected four and six indicator species in P. orientalis and Pi. elliottii communities, respectively. The α-diversity index increased with a rise in altitude and showed a wavy curve with latitude. Linear regression between the ß diversity and environmental and geographic distance indicated that the P. orientalis and Pi. elliottii understory communities tended to be dominated by different ecological processes. The partition of ß diversity indicated that both communities were dominated by turnover processes, which were caused by environmental classification or spatial constraints. This study helped to understand the diversity maintenance in the P. orientalis and Pi. elliottii understory vegetation communities, and will benefit for diversity restoration and conservation of pure conifer forests.

Human intestinal organoids from Cronkhite-Canada syndrome patients reveal link between serotonin and proliferation.

Cronkhite-Canada Syndrome (CCS) is a rare, noninherited polyposis syndrome affecting 1 in every million individuals. Despite over 50 years of CCS cases, the etiopathogenesis and optimal treatment for CCS remains unknown due to the rarity of the disease and lack of model systems. To better understand the etiology of CCS, we generated human intestinal organoids (HIOs) from intestinal stem cells isolated from 2 patients. We discovered that CCS HIOs are highly proliferative and have increased numbers of enteroendocrine cells producing serotonin (also known as 5-hydroxytryptamine or 5HT). These features were also confirmed in patient tissue biopsies. Recombinant 5HT increased proliferation of non-CCS donor HIOs and inhibition of 5HT production in the CCS HIOs resulted in decreased proliferation, suggesting a link between local epithelial 5HT production and control of epithelial stem cell proliferation. This link was confirmed in genetically engineered HIOs with an increased number of enteroendocrine cells. This work provides a new mechanism to explain the pathogenesis of CCS and illustrates the important contribution of HIO cultures to understanding disease etiology and in the identification of novel therapies. Our work demonstrates the principle of using organoids for personalized medicine and sheds light on how intestinal hormones can play a role in intestinal epithelial proliferation.

Universal F4-Modified Strategy on Metal-Organic Framework to Chemical Stabilize PVDF-HFP as Quasi-Solid-State Electrolyte.

Solid-state electrolytes (SSEs) based on metal organic framework (MOF) and polymer mixed matrix membranes (MMMs) have shown great promotions in both lithium-ion conduction and interfacial resistance in lithium metal batteries (LMBs). However, the unwanted structural evolution and the and the obscure electrochemical reaction mechanism among two phases limit their further optimization and commercial application. Herein, fluorine-modified zirconium MOF with diverse F-quantities is synthesized, denoted as Zr-BDC-Fx (x = 0, 2, 4), to assemble high performance quais-solid-state electrolytes (QSSEs) with PVDF-HFP. The chemical complexation of F-sites in Zr-BDC-F4 stabilized PVDF-HFP chains in ß-phase and disordered oscillation with enhanced charge transfer and Li transmit property. Besides, the porous confinement and electronegativity of F-groups enhanced the capture and dissociation of TFSI- anions and the homogeneous deposition of LiF solid electrolyte interphase (SEI), promoting the high-efficient transport of Li+ ions and inhibiting the growth of Li dendrites. The superb specific capacities in high-loaded Li.

Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome.

PURPOSE: Lynch syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacologic intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers. PATIENTS AND METHODS: To address this, we enrolled 21 patients with LS onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes 3 times weekly for 45 minutes versus usual care with a one-time exercise counseling session as control. We analyzed the effects of exercise on cardiorespiratory fitness, circulating, and colorectal-tissue biomarkers using metabolomics, gene expression by bulk mRNA sequencing, and spatial transcriptomics by NanoString GeoMx. RESULTS: We observed a significant increase in oxygen consumption (VO2peak) as a primary outcome of the exercise and a decrease in inflammatory markers (prostaglandin E) in colon and blood as the secondary outcomes in the exercise versus usual care group. Gene expression profiling and spatial transcriptomics on available colon biopsies revealed an increase in the colonic mucosa levels of natural killer and CD8+ T cells in the exercise group that were further confirmed by IHC studies. CONCLUSIONS: Together these data have important implications for cancer interception in LS, and document for the first-time biological effects of exercise in the immune system of a target organ in patients at-risk for cancer.

Artificial intelligence in cancer pathology: Challenge to meet increasing demands of precision medicine.

Clinical efforts on precision medicine are driving the need for accurate diagnostic, new prognostic and novel drug predictive assays to inform patient selection and stratification for disease treatment. Accumulating evidence suggests that a combination of cancer pathology and artificial intelligence (AI) can meet this requirement. In the present review, the past, present and emerging integrations of AI into cancer pathology were comprehensively reviewed, which were divided into four main groups to highlight the roles of AI­integrated cancer pathology in precision medicine. Furthermore, the unsolved problems and future challenges in AI­integrated cancer pathology were also discussed. It was found that, although AI­integrated cancer pathology could enable the amalgamation of complex morphological phenotypes with the multi­omics datasets that drove precision medicine, synergies of cancer pathology with other medical tools could be more promising for the clinic when making an accurate and rapid decision in personalized treatments for patients. It was hypothesized by the authors that exploring the potential advantages of the multimodal integration of cancer pathology, imaging­omics, protein­omics and other­omics, as well as clinical data to decide upon appropriate management and improve patient outcomes may be the most challenging issue of cancer precision medicine in the future.

Tunable Structural Coloration in Eccentric Water-in-Oil-in-Water Droplets.

Structural colors show diverse advantages such as fade resistance, eco-friendliness, iridescence, and high saturation in comparison with chemical pigments. In this paper, we show tunable structural coloration in colorless water-in-oil-in-water double emulsion droplets via total internal reflection and interference at the microscale concave interfaces. Through experimental work and simulations, we demonstrate that the shell thickness and the eccentricity of the core-shell structures are key to the successful formation of iridescent structural colors. Only eccentric thin-shell water-in-oil-in-water droplets show structural colors. Importantly, structural colors based on water-oil interfaces are readily responsive to a variety of environmental stimuli, such as osmotic pressure, temperature, magnetic fields, and light composition. This work highlights an alternative structural coloration that expands the applications of droplet-based structural colors to aqueous systems.

Fermentation of resistant starch from the starch-ferulic acid inclusion complex compared with high-amylose corn starch.

Fermentation of resistant starch from the starch-ferulic acid inclusion complex, one representative of the starch-polyphenol inclusion complex, was investigated in this study. It was found that this complex-based resistant starch, high-amylose corn starch and the mixture of ferulic acid and high-amylose corn starch were mainly utilized at the initial 6 h as indicated by the gas production and pH. Besides, the supplement of high-amylose corn starch, the mixture and the complex promoted production of short-chain fatty acids (SCFAs), reduced the ratio of Firmicutes/Bacteroidetes (F/B) and selectively stimulated the proliferation of some beneficial bacteria. Specifically, the production of SCFAs in the control and high-amylose starch, mixture and complex groups was 29.33 mM, 140.82 mM, 144.12 mM, and 167.4 mM after fermentation for 48 h, respectively. Moreover, the F/B ratio of those groups was 1.78, 0.78, 0.8 and 0.69, respectively. These results suggested that the supplement of the complex-based resistant starch led to the most SCFAs and the lowest F/B ratio (P < 0.05). Moreover, the complex group had the largest abundance of beneficial bacteria, including Bacteroides, Bifidobacterium and Lachnospiraceae_UCG-001 (P < 0.05). In summary, the resistant starch from the starch-ferulic acid inclusion complex exhibited stronger prebiotic activity than high-amylose corn starch and the mixture.

LIM Homeobox 2 Increases Adhesion-Regulating Molecule 1 Transcription to Facilitate the Pathological Progression of Oxidized Low-Density Lipoprotein-Stimulated Atherosclerotic Cell Models.

Endothelial-mesenchymal transition (EndMT) and endothelial cell apoptosis have been documented to have a role in atherosclerosis (AS) progression. To deepen knowledge in this aspect, our study investigated the effect of LIM homeobox 2 (LHX2) and adhesion-regulating molecule 1 (ADRM1) on EndMT and endothelial cell apoptosis in the oxidized low-density lipoprotein (ox-LDL) -stimulated AS cell model.Ox-LDL was utilized to treat human umbilical vein endothelial cells (HUVECs) for constructing an AS model in vitro, followed by measurement of LHX2 and ADRM1 expressions. Afterward, gain- and loss-of-function assays were performed in HUVECs, followed by detection of cell viability, invasion, migration, and apoptosis and the expression of inflammatory factors [tumor necrosis factor (TNF) -α, interleukin (IL) -1ß, and IL-6], EndMT-related proteins [CD31, vascular epithelium (VE) -cadherin, vimentin, α-smooth muscle actin (SMA), Snai1, Snai2, and Twist1], and the apoptotic protein cleaved caspase-3. Interactions between LHX2 and ADRM1 were analyzed with dual-luciferase reporter gene and chromatin immunoprecipitation assays.High levels of LHX2 and ADRM1 were observed in ox-LDL-induced HUVECs. In ox-LDL-treated HUVECs, LHX2, or ADRM1 knockdown promoted CD31 and VE-cadherin levels, viability, invasion, and migration and reduced apoptosis and the expressions of TNF-α, IL-1ß, IL-6, vimentin, α-SMA, Snai1, Snai2, Twist1, and cleaved caspase-3. Mechanistically, LHX2 bound to the ADRM1 promoter to promote ADRM1 transcription. Overexpression of ADRM1 annulled the aforementioned effects of LHX2 knockdown on ox-LDL-induced HUVECs.LHX2 facilitates the pathological progression of ox-LDL-stimulated AS cell models by increasing ADRM1 transcription.

Enhanced efficiency of launching hyperbolic phonon polaritons in stacked α-MoO3 flakes.

In this work, we reported a systemic study on the enhanced efficiency of launching hyperbolic phonon polaritons (PhPs) in stacked α-phase molybdenum trioxide (α-MoO3) flakes. By using the infrared photo-induced force microscopy (PiFM), real-space near-field images (PiFM images) of mechanically exfoliated α-MoO3 thin flakes were recorded within three different Reststrahlen bands (RBs). As referred with PiFM fringes of the single flake, PiFM fringes of the stacked α-MoO3 sample within the RB 2 and RB 3 are greatly improved with the enhancement factor (EF) up to 170%. By performing numerical simulations, it reveals that the general improvement in near-field PiFM fringes arises from the existence of a nanoscale thin dielectric spacer in the middle part between two stacked α-MoO3 flakes. The nanogap acts as a nanoresonator for prompting the near-field coupling of hyperbolic PhPs supported by each flake in the stacked sample, contributing to the increase of polaritonic fields, and verifying the experimental observations Our findings could offer fundamental physical investigations into the effective excitation of PhPs and will be helpful for developing functional nanophotonic devices and circuits.

Reciprocal interactions between alveolar progenitor dysfunction and aging promote lung fibrosis.

Aging is a critical risk factor in idiopathic pulmonary fibrosis (IPF). Dysfunction and loss of type 2 alveolar epithelial cells (AEC2s) with failed regeneration is a seminal causal event in the pathogenesis of IPF, although the precise mechanisms for their regenerative failure and demise remain unclear. To systematically examine the genomic program changes of AEC2s in aging and after lung injury, we performed unbiased single-cell RNA-seq analyses of lung epithelial cells from uninjured or bleomycin-injured young and old mice, as well as from lungs of IPF patients and healthy donors. We identified three AEC2 subsets based on their gene signatures. Subset AEC2-1 mainly exist in uninjured lungs, while subsets AEC2-2 and AEC2-3 emerged in injured lungs and increased with aging. Functionally, AEC2 subsets are correlated with progenitor cell renewal. Aging enhanced the expression of the genes related to inflammation, stress responses, senescence, and apoptosis. Interestingly, lung injury increased aging-related gene expression in AEC2s even in young mice. The synergistic effects of aging and injury contributed to impaired AEC2 recovery in aged mouse lungs after injury. In addition, we also identified three subsets of AEC2s from human lungs that formed three similar subsets to mouse AEC2s. IPF AEC2s showed a similar genomic signature to AEC2 subsets from bleomycin-injured old mouse lungs. Taken together, we identified synergistic effects of aging and AEC2 injury in transcriptomic and functional analyses that promoted fibrosis. This study provides new insights into the interactions between aging and lung injury with interesting overlap with diseased IPF AEC2 cells.

A meta-analysis: single or double dartos flap layer in tubularized incised plate urethroplasty to prevent urethrocutaneous fistula?

Backgrounds: Urethrocutaneous fistula is one of the most common complications after urethroplasty. This meta-analysis aims to evaluate the superiority of double dartos flap to single dartos flap in preventing fistula during tubularized incised plate urethroplasty (TIPU), which is one of the most frequently used operations for hypospadias. Methods: We extracted clinical trials under the following included criteria: (1) children with TIPU; (2) a comparison of single and double flap layer; and (3) record of complications with the following excluded criteria: (1) non-comparison and (2) lack of data. Finally, 13 studies from PubMed, Cochrane Library, Scopus, and Embase have been investigated, with a total of 1,185 patients from 2005 to 2022. The quality assessment was conducted according to the Cochrane handbook and the Newcastle-Ottawa scale. A mixed-effect model was utilized to weigh the risk of fistula, phallic rotation, meatal stenosis, and wound dehiscence by the Review Manager V.5.4 software. Results: The double dartos flap layer group excels in descending the risk of postoperative fistula [odds ratio (OR) = 9.56; 95% confidence interval (CI) (4.76, 19.22); P < 0.00001] and phallic rotation [OR = 31.26; 95% CI (9.60, 101.84); P < 0.00001], while there are no differences in the rate of meatal stenosis [OR = 1.49; 95% CI (0.73, 2.70); P = 0.31] and wound dehiscence [OR = 2.30; 95% CI (0.80, 6.63); P = 0.12]. Conclusions: The routine utility of a double dartos flap layer is recommended as a potential treatment during the tubularized incised plate urethroplasty. Systematic Review Registration: identifier PROSPERO CRD42022366294.