The predictive value of delta-like3 and serum NSE in evaluating chemotherapy response and prognosis in patients with advanced small cell lung carcinoma: An observational study.

Lung cancer is one of the most malignant tumors with fastest morbidity and mortality. Small cell lung cancer (SCLC) is the most malignant pathological type of lung cancer with early metastasis and poor prognosis. At present, there is a lack of effective indicators to predict prognosis of SCLC patients. Delta-like 3 protein (DLL3) is selectively expressed on the surface of SCLC and is involved in proliferation and invasion. Neuron-specific enolase (NSE) is an enolase isoenzyme that is generally regarded as a biomarker for SCLC and may correlate with stage of SCLC, prognosis and chemotherapy response. NSE can be influenced by different types of factors. To explore the associations between expression levels of DLL3 in tumor tissues with platinum/etoposide chemotherapy response, and assess the prognostic values of DLL3, NSE and other potential prognostic factors in advanced SCLC patients were herein studied. Ninety-seven patients diagnosed with SCLC in Zhongda Hospital from 2014 to 2020 were enrolled in the study. Serum NSE levels were tested using ELISA methods before any treatment. The expression of DLL3 in tumor tissue was detected by Immunohistochemistry (IHC). We investigated the relationship of DLL3 expression with chemotherapy and survival. Progression free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Multivariate Cox-proportional hazard regression was used to identify predictors of PFS and OS. DLL3 was detected in 84.5% (82/97) of all patients' tumor samples by IHC, mainly located on the surface of SCLC cells. Lower DLL3 expression was associated with longer PFS and better chemotherapy response. OS had no significant differences. Multivariate analysis by Cox Hazard model showed that, high DLL3 expression and maximum tumor size >5 cm were independent risk factors for PFS, where NSE < 35 ng/mL and age < 70 were independent prognostic factors for OS. Early stage was independent prognostic factors for PFS and OS (P < .05 log-rank). DLL3 was expressed in the most of SCLCs. DLL3 expression level in the tumor and NSE level in the serum may be useful biomarkers to predict the prognosis of SCLC. DLL3 may be a potential therapeutic target for SCLC in the future.

Treatment of mixed and refractory post-tuberculosis tracheobronchial stenosis with L-shaped silicone stents: case series and a literature review.

The two patients included in the study had mixed and refractory post-tuberculosis tracheobronchial stenosis (PTTS), having experienced unsuccessful interventional therapies such as balloon dilation and V-shaped stent placement before the operation. Following the secure placement of L-shaped silicone stents, examinations with a fiberbronchoscope during the first and third months post-operation revealed a significant reduction in bronchial mucosa inflammation for both patients. Additionally, the opening diameter of the upper and lower branch segments increased, and chest CT scans indicated a noticeable absorption of left pulmonary lesions. Three months post-operation, fiberbronchoscopy confirmed the stable fixation of the stent without any movement. The patients exhibited substantial improvements in pulmonary function, dyspnea index, and blood gas analysis, with no reported adverse complications. After 7 months, a follow-up fiberbronchoscope for one case revealed excellent stent fixation. Simultaneously, the chest CT scan indicated favorable re-expansion. The placement of L-shaped silicone stents proves effective in preventing displacement, alleviating airway stenosis or obstruction, and ensuring the safety and efficacy of PTTS treatment - particularly in cases where V-shaped silicone stent placement has failed. To our knowledge, this is the first study describing the L-shaped silicone stent in two patients with PTTS.

Successful treatment of severe airway narrowing due to tuberculosis using special L-shaped silicone stentsThis article tells the story of two patients who suffered from a complex lung condition called post-tuberculosis tracheobronchial stenosis (PTTS). Imagine your airways - the tubes that carry air to your lungs - getting severely scarred and narrowed due to a past bout with tuberculosis. These two patients had tried previous treatments like balloon dilation (where a small balloon is inflated inside the narrowed airway to widen it) and using V-shaped stents (flexible supports placed in the airway to keep it open), but these methods didn't provide lasting relief. In this innovative approach, doctors used L-shaped silicone stents specifically designed to fit in the affected parts of the patients' airways. After placing these stents, regular checks showed remarkable improvements. The swelling in the airway lining reduced significantly, and the openings leading to the upper and lower parts of the lungs got wider. Chest X-rays (CT scans) even showed that the patient's left lung was healing well. Three months later, the stents stayed firmly in place, and neither patient experienced any problems. Breathing became easier, lung function tests improved, and blood tests showed better oxygen levels. Seven months down the line, one patient continued to do extremely well, with the stent securely fixed and the chest scan showing good lung expansion. This groundbreaking study shows that using L-shaped silicone stents can effectively treat PTTS when other methods fail. Not only do they stay in place, preventing blockages, but they also safely and effectively alleviate narrowing of the airways. It's the first time such L-shaped stents have been used successfully in PTTS patients, offering new hope for those facing similar challenges.

Tunable abundant valley Hall effect and chiral spin-valley locking in Janus monolayer VCGeN4.

It is both conceptually and practically fascinating to explore fundamental research studies and practical applications of two-dimensional systems with the tunable abundant valley Hall effect. In this work, based on first-principles calculations, the tunable abundant valley Hall effect is proved to appear in Janus monolayer VCGeN4. When the magnetization is along the out-of-plane direction, VCGeN4 is an intrinsic ferromagnetic semiconductor with a valley feature. The intriguing spontaneous valley polarization exists in VCGeN4 due to the common influence of broken inversion and time-reversal symmetries, which makes it easier to realize the anomalous valley Hall effect. Furthermore, we observe that the valley-non-equilibrium quantum anomalous Hall effect is driven by external strain, which is located between two half-valley-metal states. When reversing the magnetization, the spin flipping makes the position of the edge state to change from one valley to another valley, demonstrating an intriguing behavior known as chiral spin-valley locking. Although the easy magnetic axis orientation is along the in-plane direction, we can utilize an external magnetic field to transform the magnetic axis orientation. Moreover, it is found that the valley state, electronic and magnetic properties can be well regulated by the electric field. Our works explore the mechanism of the tunable abundant valley Hall effect by applying an external strain and electric field, which provides a perfect platform to investigate the spin, valley, and topology.

Nomogram for predicting postoperative ileus after radical cystectomy and urinary diversion: a retrospective single-center study.

OBJECTIVE: To predict the incidence of postoperative ileus in bladder cancer patients after radical cystectomy. METHODS: We retrospectively analyzed the perioperative data of 452 bladder cancer patients who underwent radical cystectomy with urinary diversion at the Second Hospital of Tianjin Medical University between 2016 and 2021. Univariate and multivariate logistic regression were used to identify the risk factors for postoperative ileus. Finally, a nomogram model was established and verified based on the independent risk factors. RESULTS: Our study revealed that 96 patients (21.2%) developed postoperative ileus. Using multivariate logistic regression analysis, we found that the independent risk factors for postoperative ileus after radical cystectomy included age > 65.0 years, high or low body mass index, constipation, hypoalbuminemia, and operative time. We established a nomogram prediction model based on these independent risk factors. Validation by calibration curves, concordance index, and decision curve analysis showed a strong correlation between predicted and actual probabilities of occurrence. CONCLUSION: Our nomogram prediction model provides surgeons with a simple tool to predict the incidence of postoperative ileus in bladder cancer patients undergoing radical cystectomy.

Large-scale Prospective Validation Study of a Multiplex RNA Urine Test for Noninvasive Detection of Upper Tract Urothelial Carcinoma.

BACKGROUND: Current approaches for diagnosis and monitoring of upper tract urothelial carcinoma (UTUC) are often invasive, costly, and not efficient for early-stage and low-grade tumors. OBJECTIVE: To validate a noninvasive urine-based RNA test for accurate UTUC diagnosis. DESIGN, SETTING, AND PARTICIPANTS: Urine samples were prospectively collected from 61 patients with UTUC and 99 controls without urothelial carcinomas, in five clinical centers between October 2022 and August 2023 prior to any invasive test (cystoscope or ureteroscope) or treatment. All samples were analyzed with a urine-based RNA test composed of eight genes (CA9, CCL18, ERBB2, IGF2, MMP12, PPP1R14D, SGK2, and SWINGN). The test results were presented with a risk score for each participant, which was applied to categorize patients into low- or high-risk groups. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The diagnosis of UTUC was based mainly on preoperative radiological examination criteria and confirmed by postoperative pathological results. The recursive feature elimination and support vector machine algorithms, χ2, and Student t test were used. RESULTS AND LIMITATIONS: The eight-gene urine test accurately detected UTUC patients and controls with an area under the curve (AUC) of 0.901 in a single-center testing cohort (n = 93) and an AUC of 0.926 in a multicenter clinical validation cohort (n = 66). In the merged validation cohort, the eight-gene urine test achieved high sensitivity of 90.16%, specificity of 88.89%, and overall accuracy of 89.38%. Remarkably, excellent performance was achieved in 11 low-grade UTUC patients with accuracy of 100%. However, this study collected the urine of UTUC patients only at a single preoperative time point and did not perform continuous tests during the pathological process of UTUC in the surveillance population. CONCLUSIONS: Our results demonstrated that the eight-gene urine test can differentiate accurately between UTUC and other urological diseases with high sensitivity and specificity. In clinical practice, it may be used for identifying UTUC patients effectively, leading to reduced reliance on ureteroscopy and blind surgery. PATIENT SUMMARY: In this study, we investigated a multiplex RNA urine test for noninvasive upper tract urothelial carcinoma (UTUC) diagnosis before treatment. We found that the risk scores derived from the multiplex RNA urine test differed significantly between UTUC patients and corresponding controls.

Discovery of lung adenocarcinoma tumor antigens and ferroptosis subtypes for developing mRNA vaccines.

mRNA vaccines are becoming a feasible alternative for treating cancer. To develop mRNA vaccines against LUAD, potential antigens were identified and LUAD ferroptosis subtypes distinguished for selecting appropriate patients. The genome expression omnibus, cancer genome atlas (TCGA) and FerrDB were used to collect gene expression profiles, clinical information, and the genes involved in ferroptosis, respectively. cBioPortal was used to visualize and compare genetic alterations, GEPIA2 to calculate prognostic factors of the selected antigens, and TIMER to visualize the relationship between potential antigens and tumor immune cell infiltration. Consensus clustering analysis was utilized to identify ferroptosis subtypes and their prognostic value assessed by Log-rank and cox regression tests. The modules of ferroptosis-related gene screening were conducted by weight gene co-expression network analysis. The LUAD ferroptosis landscape was visualized through dimensionality reduction and graph learning. Six tumor antigens had obvious LUAD-mutations, positively correlated with different antigen-presenting cells, and might induce tumor cell ferroptosis. LUAD patients were stratified into three ferroptosis subtypes (FS1, FS2, and FS3) according to diverse molecular, cellular, and clinical characteristics. FS3 showed the highest tumor mutation burden and the most somatic mutations, deemed potential indicators of mRNA vaccine effectiveness. Moreover, different ferroptosis subtypes expressed distinct immune checkpoints and immunogenic cell death modulators. AGPS, NRAS, MTDH, PANX1, NOX4, and PPARD are potentially suitable for mRNA vaccinations against LUAD, specifically in patients with FS3 tumors. This study defines vaccination candidates and establishes a theoretical basis for LUAD mRNA vaccinations.

miR-34c-5p inhibited fibroblast proliferation, differentiation and epithelial-mesenchymal transition in benign airway stenosis via MDMX/p53 pathway.

Benign airway stenosis (BAS) means airway stenosis or obstruction that results from a variety of non-malignant factors, including tuberculosis, trauma, benign tumors, etc. In consideration of the currently limited research on microRNAs in BAS, this study aimed to explore the role and mechanism of miR-34c-5p in BAS. The expression of miR-34c-5p in BAS granulation tissues showed a significant down-regulation compared with the normal control group. Moreover, miR-34c-5p mimics suppressed the proliferation and differentiation of human bronchial fibroblasts (HBFs) and the epithelial-mesenchymal transition (EMT) of human bronchial epithelial cells (HBE). Conversely, miR-34c-5p inhibitors aggravated those effects. A dual-luciferase reporter assay confirmed that miR-34c-5p can target MDMX rather than Notch1. The over-expression of MDMX can reverse the inhibiting effect of miR-34c-5p on HBFs proliferation, differentiation and EMT. Furthermore, the expressions of tumor protein (p53) and PTEN were down-regulated following the over-expression of MDMX. In addition, the expressions of PI3K and AKT showed an up-regulation. In conclusion, miR-34c-5p was down-regulated in BAS and may inhibit fibroblast proliferation differentiation and EMT in BAS via the MDMX/p53 signaling axis. These findings expand the understanding of the role of miR-34c-5p and will help develop new treatment strategies for BAS.

Novel valley character and tunable quasi-half-valley metal state in Janus monolayer VSiGeP4.

The manipulation and regulation of valley characteristics have aroused widespread interest in emerging information fields and fundamental research. Realizing valley polarization is one crucial issue for spintronic and valleytronic applications, the concepts of a half-valley metal (HVM) and ferrovalley (FV) materials have been put forward. Then, to separate electron and hole carriers, a fresh concept of a quasi-HVM (QHVM) has been proposed, in which only one type of carrier is valley polarized for electron and hole carriers. Based on first-principles calculations, we demonstrate that the Janus monolayer VSiGeP4 has QHVM character. To well regulate the QHVM state, strain engineering is utilized to adjust the electronic and valley traits of monolayer VSiGeP4. In the discussed strain range, monolayer VSiGeP4 always favors the ferromagnetic ground state and out-of-plane magnetization, which ensures the appearance of spontaneous valley polarization. It is found that the QHVM state can be induced in different electronic correlations (U), and the strain can effectively tune the valley, magnetic, and electronic features to maintain the QHVM state under various U values. Our work opens up a new research idea in the design of multifunctional spintronic and valleytronic devices.

Elevated Expression of NOP16 as a Novel Prognostic Biomarker of Prostate Cancer.

OBJECTIVE: To investigate the role of NOP16, a target gene of estrogen and c-Myc, in prostate cancer (PCa). METHODS: The expressions of NOP16 in PCa and benign prostate hyperplasia (BPH) tissues, PC-3 and RWPE-1 cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot respectively. The expressions of NOP16 in BPH and PCa paraffin-embedded tissues were assessed by immunohistochemistry (IHC). The Cancer Genome Atlas (TCGA) database was used to analyze the effect of NOP16 gene expression on the disease-free survival of PCa patients. CCK-8, wound healing, transwell assays and flow cytometric analysis were used to assess the changes of proliferation, migration, invasion and apoptosis of PC-3 cells respectively after knocking down NOP16 in vitro. Gene ontology (GO) and gene set enrichment analysis (GSEA) were used to analyze the RNA sequencing data followed by knocking down NOP16 in PC-3 cells. Mouse models were used to explore the effect of NOP16 on PC-3 subcutaneous tumor growth in vivo. RESULTS: The NOP16 expression was significantly higher in PCa tissues than that in BPH tissues and significantly higher in PC-3 cells than in RWPE-1 cells. PCa patients with low NOP16 expression have a longer disease-free survival than that with high NOP16 expression. Ribosome biogenesis in eukaryotes, ECM-receptor interaction, PTEN and VEGF signaling pathways may be changed in the NOP16 knockdown group than control. Knockdown of NOP16 could significantly inhibit the proliferation, migration and invasion of PC-3 cells in vitro and in vivo. Low expression of NOP16 could reduce the total protein synthesis and induce the apoptosis of PC-3 cells. CONCLUSION: NOP16 may be expected to be a novel biomarker for predicting the occurrence and development of PCa, and may become a target for the treatment of PCa.

The Present and Future of Artificial Intelligence in Urological Cancer.

Artificial intelligence has drawn more and more attention for both research and application in the field of medicine. It has considerable potential for urological cancer detection, therapy, and prognosis prediction due to its ability to choose features in data to complete a particular task autonomously. Although the clinical application of AI is still immature and faces drawbacks such as insufficient data and a lack of prospective clinical trials, AI will play an essential role in individualization and the whole management of cancers as research progresses. In this review, we summarize the applications and studies of AI in major urological cancers, including tumor diagnosis, treatment, and prognosis prediction. Moreover, we discuss the current challenges and future applications of AI.

Low-dose antimony exposure promotes prostate cancer proliferation by inhibiting ferroptosis via activation of the Nrf2-SLC7A11-GPX4 pathway.

Antimony (Sb) is a typical environmental pollutant. With the development of industrialization, antimony is widely used in daily life and enters the human body through the food chain, water source, air pollution, and other channels. The risk of antimony exposure has emerged as one of the public's major health concerns. Current research on antimony shows that antimony has certain biological toxicity, and antimony exposure may be one of the carcinogenic risk factors for bladder cancer, prostate cancer (PCa), and other cancers. But the molecular mechanism of antimony exposure in PCa is still unclear. Our results showed that serum antimony levels were significantly higher in PCa patients than in benign prostatic hyperplasia (BPH), and high levels of serum antimony were associated with poorer prognosis in PCa. We demonstrate that antimony exposure promotes PCa progression in vivo and in vitro. In addition, our results also showed that low-dose antimony exposure resulted in increased GSH, increased GPX4 expression, and decreased Fe2+. Since GPX4 and Fe2+ are important molecular features in the mechanism of ferroptosis, we further found that low-dose antimony exposure can inhibit RSL3-induced ferroptosis and promote PCa proliferation. Finally, our study demonstrates that low-dose antimony exposure promotes Nrf2 expression, increases the expression level of SLC7A11, and then increases the expression of GPX4, inhibits ferroptosis, and promotes PCa progression. Taken together, our experimental results suggest that low-dose antimony exposure promotes PCa cell proliferation by inhibiting ferroptosis through activation of the Nrf2-SLC7A11-GPX4 pathway. These findings highlight the link between low-dose antimony exposure and the Nrf2-SLC7A11-GPX4 ferroptosis pathway, providing a new potential direction for the prevention and treatment of PCa.

Quantum anomalous Hall effect with a high and tunable Chern number in monolayer NdN2.

Due to the presence of dissipationless edge states, the quantum anomalous Hall (QAH) insulator has garnered significant attention for both fundamental research and practical application. However, the majority of QAH insulators suffer from a low Chern number (C = 1), and the Chern number is basically unadjustable, which constrains their potential application in spintronic devices. Here, based on a tight-binding model and first-principles calculations, we propose that two-dimensional (2D) ferromagnetic monolayer NdN2 exhibits a high-Chern-number QAH effect with C = ±3, accompanied by a nontrivial band gap of 97.4 meV. More importantly, by manipulating the magnetization orientation in the xz plane, the Chern number of 2D NdN2 can be further tuned between C = ±3 and C = ±1. When the magnetization vector is confined to the xy plane, the monolayer NdN2 would exhibit either a Dirac half-semimetal or in-plane QAH phase. Moreover, the QAH effect with a higher Chern number C = 9 can be achieved by constructing a multilayer van der Waals heterostructure composed of monolayers NdN2 and BN with alternative stacking order. These findings provide a reliable platform for exploring the novel QAH effect and developing high-performance topological devices.

Implications of ferroptosis in silver nanoparticle-induced cytotoxicity of macrophages.

Metal nanoparticles (NPs) are widely used in daily life and commercial activities owing to their unique physicochemical properties. Consequently, there is an increasing risk of daily and occupational exposure to metal NPs, which raises concerns regarding their health hazards. Programmed cell deaths (PCDs) have been clarified to be involved in metal NP-induced cytotoxicity, including apoptosis, autophagy, and pyroptosis. However, whether and how ferroptosis, a newly recognized PCD, contributes to metal NP-induced cell death remain unclear. In this study, we investigated the ferroptotic effects of two representative metal NPs, silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs), on macrophages in vitro. Our results revealed that AgNPs, rather than AuNPs, induced non-apoptotic PCD, accompanied by lipid peroxidation and iron homeostasis disorders, which are two hallmarks of ferroptosis, in macrophages. Treatment with a ferroptosis inhibitor (ferrostatin-1) and iron chelator (deferoxamine) reversed AgNP-induced PCD, corroborating the induction of ferroptosis upon exposure to AgNPs. Moreover, our results revealed that smaller AgNPs elicited greater ferroptotic effects on macrophages than larger ones. Importantly, ferroptosis in AgNP-treated macrophages was mainly triggered by AgNPs per se rather than by Ag ions. Overall, our study highlights the ferroptotic effects elicited by AgNPs in macrophages, which will promote the understanding of their cytotoxic effects and facilitate the safer design of metal nanoproducts.

Electronic-correlation induced sign-reversible Berry phase and quantum anomalous valley Hall effects in Janus monolayer OsClBr.

Topological phase transition can be induced by electronic correlation effects combined with spin-orbit coupling (SOC). Here, based on the first-principles calculations +U approach, the influence of electronic correlation effects and SOC on topological and electronic properties of the Janus monolayer OsClBr is investigated. With intrinsic out-of-plane (OOP) magnetic anisotropy, the Janus monolayer OsClBr exhibits a sequence of states, namely, the ferrovalley (FV) to half-valley-metal (HVM) to quantum anomalous valley Hall effect (QAVHE) to HVM to FV states with increasing U values. The QAVHE is characterized by a chiral edge state linking the conduction and valence bands with a Chern number C = 1, which is closely associated with the band inversion between dx2-y2/dxy and dz2 orbitals, and sign-reversible Berry curvature. The section with larger U values (2.31-2.35 eV) is very essential for determining the new HVM and QAVHE states, and also proves that a strong electron correlation effect exists in the interior of the Janus monolayer OsClBr. When taking into consideration a representative U value (U = 2.5 eV), a valley polarization value of 157 meV can be observed, which can be switched by reversing the magnetization direction of Os atoms. It is noteworthy that the Curie temperature (TC) strongly depends on the electronic correlation effects. Our work provides a comprehensive discussion on the electronic and topological properties of the Janus monolayer OsClBr, and demonstrates that the electronic correlation effects combined with SOC can drive the emergence of QAVHE, which will open up new opportunities for valleytronic, spintronic, and topological nanoelectronic applications.

Associations between diet and incidence risk of lung cancer: A Mendelian randomization study.

Background: Observational studies have revealed associations between diet and lung cancer. However, it is unclear whether the association is disturbed by confounding factors. We used a two-sample Mendelian randomization (MR) method to characterize the associations between diet and the lung cancer risk (including 3 subtypes: lung adenocarcinoma (LA), squamous cell lung carcinoma (SqCLC), and small cell lung cancer (SCLC)). Materials and methods: Data on 20 diets were screened from the UK Biobank. Lung cancer data came from a large meta-analysis of 85,716 individuals. The inverse-variance weighted method was used as the main analysis. Sensitivity analysis was also used to explain the different multiplicity patterns of the final model. Results: Our results showed significant evidence that 3 diets were associated with lung cancer [odds ratio (OR): 0.271, 95% confidence interval (CI): 0.150-0.488, p = 1.46 × 10-4, dried fruit; OR: 3.010, 95% CI: 1.608-5.632, p = 5.70 × 10-4, beer] and SqCLC (OR: 0.135, 95% CI: 0.062-0.293, p = 2.33 × 10-5, dried fruit; OR: 0.485, 95% CI: 0.328-0.717, p = 2.9 × 10-4, cheese). There were also suggestive correlations between 5 dietary intakes and lung cancer (OR: 0.441, 95% CI: 0.250-0.778, p = 0.008, cereal; OR: 2.267, 95% CI: 1.126-4.564, p = 0.022, beef), LA (OR: 0.494, 95% CI: 0.285-0.858, p = 0.012, dried fruit; OR: 3.536, 95% CI: 1.546-8.085, p = 0.003, beer) and SCLC (OR: 0.006, 95% CI: 0.000-0.222, p = 0.039, non-oily fish; OR: 0.239, 95% CI: 0.086-0.664, p = 0.006, dried fruit). No other association between diet and lung cancer was observed. Conclusion: Our study preliminary found that cheese, dried fruit, and beer intake were significantly associated with the risk of lung cancer or its subtypes, while cereal, beef, and non-oily fish intake were suggestively associated with the risk of lung cancer or its subtypes. Well-designed prospective studies are still needed to confirm our findings in the future.

Clinical values of metagenomic next-generation sequencing in patients with severe pneumonia: a systematic review and meta-analysis.

Background: Clinical values of metagenomic next-generation sequencing (mNGS) in patients with severe pneumonia remain controversial. Therefore, we conduct this meta-analysis to evaluate the diagnostic performance of mNGS for pathogen detection and its role in the prognosis of severe pneumonia. Methods: We systematically searched the literature published in PubMed, Embase, Cochrane Library, Web of Science, Clinical Trials.gov, CNKI, Wanfang Data, and CBM from the inception to the 28th September 2022. Relevant trials comparing mNGS with conventional methods applied to patients with severe pneumonia were included. The primary outcomes of this study were the pathogen-positive rate, the 28-day mortality, and the 90-day mortality; secondary outcomes included the duration of mechanical ventilation, the length of hospital stay, and the length of stay in the ICU. Results: Totally, 24 publications with 3220 patients met the inclusion criteria and were enrolled in this study. Compared with conventional methods (45.78%, 705/1540), mNGS (80.48%, 1233/1532) significantly increased the positive rate of pathogen detection [OR = 6.81, 95% CI (4.59, 10.11, P < 0.001]. The pooled 28-day and 90-day mortality in mNGS group were 15.08% (38/252) and 22.36% (36/161), respectively, which were significantly lower than those in conventional methods group 33.05% (117/354) [OR = 0.35, 95% CI (0.23, 0.55), P < 0.001, I2 = 0%] and 43.43%(109/251) [OR = 0.34, 95% CI (0.21, 0.54), P < 0.001]. Meanwhile, adjusted treatment based on the results of mNGS shortened the length of hospital stay [MD = -2.76, 95% CI (- 3.56, - 1.96), P < 0.001] and the length of stay in ICU [MD = -4.11, 95% CI (- 5.35, - 2.87), P < 0.001]. Conclusion: The pathogen detection positive rate of mNGS was much higher than that of conventional methods. Adjusted treatment based on mNGS results can reduce the 28-day and 90-day mortality of patients with severe pneumonia, and shorten the length of hospital and ICU stay. Therefore, mNGS advised to be applied to severe pneumonia patients as early as possible in addition to conventional methods to improve the prognosis and reduce the length of hospital stay.

Spontaneous valley polarization and valley-nonequilibrium quantum anomalous Hall effect in Janus monolayer ScBrI.

Topology and ferrovalley (FV) are two essential concepts in emerging device applications and the fundamental research field. To date, relevant reports are extremely rare about the coupling of FV and topology in a single system. By Monte Carlo (MC) simulations and first-principles calculations, a stable intrinsic FV ScBrI semiconductor with high Curie temperature (TC) is predicted. Because of the combination of spin-orbital coupling (SOC) and exchange interaction, the Janus monolayer ScBrI shows a spontaneous valley polarization of 90 meV, which is located in the top valence band. For the magnetization direction perpendicular to the plane, the changes from FV to half-valley-metal (HVM), to valley-nonequilibrium quantum anomalous Hall effect (VQAHE), to HVM, and to FV can be induced by strain engineering. It is worth noting that there are no particular valley polarization and VQAHE states for in-plane (IP) magnetic anisotropy. By obtaining the real magnetic anisotropy energy (MAE) under different strains, due to spontaneous valley polarization, intrinsic out-of-plane (OOP) magnetic anisotropy, a chiral edge state, and a unit Chern number, the VQAHE can reliably appear between two HVM states. The increasing strains can induce VQAHE, which can be clarified by a band inversion between dx2-y2/dxy and dz2 orbitals, and a sign-reversible Berry curvature. Once synthesized, the Janus monolayer ScBrI would find more significant applications in topological electronic, valleytronic, and spintronic nanodevices.

Strain-tunable skyrmions in two-dimensional monolayer Janus magnets.

The Dzyaloshinskii-Moriya interaction (DMI), which only exists in noncentrosymmetric systems, plays an important role in the formation of exotic chiral magnetic states. However, the absence of the DMI occurs in most two-dimensional (2D) magnetic materials due to their intrinsic inversion symmetry. Here, by using first-principles calculations, we demonstrate that a significant DMI can be obtained in a series of Janus monolayers of dichalcogenides XSeTe (X = Nb, Re) in which the difference between Se and Te on the opposite sides of X breaks the inversion symmetry. Remarkably, the DMI amplitudes of NbSeTe (1.78 meV) and ReSeTe (4.82 meV) are larger than the experimental value of Co/graphene (0.16 meV), and NbSeTe and ReSeTe monolayers have a high Curie temperature of 1023 K and 689 K, respectively. Through the micromagnetic simulation of XSeTe (X= Nb, Re) simulations, we also find that the ReSeTe monolayer can performance for skyrmion states by applying an external magnetic field, and importantly, the skyrmion states can be regulated and controlled under external strain. The findings pave the way for device concepts using chiral magnetic structures in specially designed 2D ferromagnetic materials.

HOXB3 drives WNT-activation associated progression in castration-resistant prostate cancer.

Enabled resistance or innate insensitiveness to antiandrogen are lethal for castration-resistant prostate cancer (CRPC). Unfortunately, there seems to be little can be done to overcome the antiandrogen resistance because of the largely unknown mechanisms. In prospective cohort study, we found that HOXB3 protein level was an independent risk factor of PSA progression and death in patients with metastatic CRPC. In vivo, upregulated HOXB3 contributed to CRPC xenografts progression and abiraterone resistance. To uncover the mechanism of HOXB3 driving tumor progression, we performed RNA-sequencing in HOXB3 negative (HOXB3-) and HOXB3 high (HOXB3 + ) staining CRPC tumors and determined that HOXB3 activation was associated with the expression of WNT3A and enriched WNT pathway genes. Furthermore, extra WNT3A and APC deficiency led HOXB3 to be isolated from destruction-complex, translocated to nuclei, and then transcriptionally regulated multiple WNT pathway genes. What's more, we also observed that the suppression of HOXB3 could reduce cell proliferation in APC-downregulated CRPC cells and sensitize APC-deficient CRPC xenografts to abiraterone again. Together, our data indicated that HOXB3 served as a downstream transcription factor of WNT pathway and defined a subgroup of CRPC resistant to antiandrogen which would benefit from HOXB3-targeted therapy.

Nucleus-Targeting Manganese Dioxide Nanoparticles Coated with the Human Umbilical Cord Mesenchymal Stem Cell Membrane for Cancer Cell Therapy.

Recently, development of drug delivery systems for accurate delivery of antitumor drugs to tumor sites to improve their antitumor efficacy has attracted great interest in the area of cancer immunotherapy. In this report, an intelligent biodegradable hollow manganese dioxide (HMnO2) nanoparticle (NP) with a human umbilical cord mesenchymal stem cell (hUC-MSC) membrane coating was designed to exert efficient chemo-immunotherapy for cancer treatment. A TAT peptide-modified membrane structure was constructed for nuclear targeting. Our findings showed that this new nanoreactor inherited the active targeting capability of MSCs and exhibited tumoritropic accumulation significantly at the cancerous parts. Compared with other formulations, intravenous injection of the NPs markedly inhibited tumor growth, relapse, and metastasis. Moreover, we found that the NPs effectively boosted dendritic cell maturation and recruited effector T cells into tumors. Overall, this work demonstrates the great potential of applying MSC membrane-coated manganese dioxide NPs as nucleus-targeting nanocarriers in cancer chemo-immunotherapy.