The expansion of MDSCs induced by exosomal PD-L1 promotes the progression of gastric cancer.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are the major factor in gastric cancer (GC) immune evasion. Nevertheless, the molecular process underlying the expansion of MDSCs induced by tumor-derived exosomes (TDEs) remains elusive. METHODS: The levels of exosomal and soluble PD-L1 in ninety GC patients were examined via enzyme-linked immunosorbent assay (ELISA) to determine their prognostic value. To investigate the correlation between exosomal PD-L1 and MDSCs, the percentage of MDSCs in the peripheral blood of 57 GC patients was assessed via flow cytometry. Through ultracentrifugation, the exosomes were separated from the GC cell supernatant and detected via Western blotting, nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). The function of exosomal PD-L1 in MDSCs was evaluated via immunofluorescence, Western blotting and flow cytometry in a GC cell-derived xenograft (CDX) model. RESULTS: The overall survival (OS) of GC patients in the high exosomal PD-L1 group was significantly lower than that of patients in the low exosomal PD-L1 group (P = 0.0042); however, there was no significant correlation between soluble PD-L1 and OS in GC patients (P = 0.0501). Furthermore, we found that the expression of exosomal PD-L1 was positively correlated with the proportions of polymorphonuclear MDSCs (PMN-MDSCs, r = 0.4944, P < 0.001) and monocytic MDSCs (M-MDSCs, r = 0.3663, P = 0.005) in GC patients, indicating that exosomal PD-L1 might induce immune suppression by promoting the aggregation of MDSCs. In addition, we found that exosomal PD-L1 might stimulate MDSC proliferation by triggering the IL-6/STAT3 signaling pathway in vitro. The CDX model confirmed that exosomal PD-L1 could stimulate tumor development and MDSC amplification. CONCLUSIONS: Exosomal PD-L1 has the potential to become a prognostic and diagnostic biomarker for GC patients. Mechanistically, MDSCs can be activated by exosomal PD-L1 through IL-6/STAT3 signaling and provide a new strategy against GC through the use of exosomal PD-L1 as a treatment target.

Heat shock proteins as hallmarks of cancer: insights from molecular mechanisms to therapeutic strategies.

Heat shock proteins are essential molecular chaperones that play crucial roles in stabilizing protein structures, facilitating the repair or degradation of damaged proteins, and maintaining proteostasis and cellular functions. Extensive research has demonstrated that heat shock proteins are highly expressed in cancers and closely associated with tumorigenesis and progression. The "Hallmarks of Cancer" are the core features of cancer biology that collectively define a series of functional characteristics acquired by cells as they transition from a normal state to a state of tumor growth, including sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, enabled replicative immortality, the induction of angiogenesis, and the activation of invasion and metastasis. The pivotal roles of heat shock proteins in modulating the hallmarks of cancer through the activation or inhibition of various signaling pathways has been well documented. Therefore, this review provides an overview of the roles of heat shock proteins in vital biological processes from the perspective of the hallmarks of cancer and summarizes the small-molecule inhibitors that target heat shock proteins to regulate various cancer hallmarks. Moreover, we further discuss combination therapy strategies involving heat shock proteins and promising dual-target inhibitors to highlight the potential of targeting heat shock proteins for cancer treatment. In summary, this review highlights how targeting heat shock proteins could regulate the hallmarks of cancer, which will provide valuable information to better elucidate and understand the roles of heat shock proteins in oncology and the mechanisms of cancer occurrence and development and aid in the development of more efficacious and less toxic novel anticancer agents.

PLXNA1 confers enzalutamide resistance in prostate cancer via AKT signaling pathway.

Although targeting the androgen signaling pathway by androgen receptor (AR) inhibitors, including enzalutamide, has shown therapeutic effectiveness, inevitable emergence of acquired resistance remains a critical challenge in the treatment of advanced prostate cancer (PCa). Recognizing targetable genomic aberrations that trigger endocrine treatment failure holds great promise for advancing therapeutic interventions. Here, we characterized PLXNA1, amplified in a subset of PCa patients, as a contributor to enzalutamide resistance (ENZR). Elevated PLXNA1 expression facilitated PCa proliferation under enzalutamide treatment due to AKT signaling activation. Mechanistically, PLXNA1 recruited NRP1 forming a PLXNA1-NRP1 complex, which in turn potentiated the phosphorylation of the AKT. Either inhibiting PLXNA1-NRP1 complex with an NRP1 inhibitor, EG01377, or targeting PLXNA1-mediated ENZR with AKT inhibitors, abolished the pro-resistance phenotype of PLXNA1. Taken together, combination of AKT inhibitor and AR inhibitors presents a promising therapeutic strategy for PCa, especially in advanced PCa patients exhibiting PLXNA1 overexpression.

Biosensor-based active ingredient recognition system for screening potential small molecular Severe acute respiratory syndrome coronavirus 2 entry blockers targeting the spike protein from Rugosa rose.

The traditional formulation Hanchuan zupa granules (HCZPs) have been widely used for controlling coronavirus disease 2019 (COVID-19). However, its active components remain unknown. Here, HCZP components targeting the spike receptor-binding domain (S-RBD) of SARS-CoV-2 were investigated using a surface plasmon resonance (SPR) biosensor-based active ingredient recognition system (SPR-AIRS). Recombinant S-RBD proteins were immobilized on the SPR chip by amine coupling for the prescreening of nine HCZP medicinal herbs. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) identified gallic acid (GA) and methyl gallate (MG) from Rosa rugosa as S-RBD ligands, with KD values of 2.69 and 0.95 µM, respectively, as shown by SPR. Molecular dynamics indicated that GA formed hydrogen bonds with G496, N501, and Y505 of S-RBD, and MG with G496 and Y505, inhibiting S-RBD binding to angiotensin-converting enzyme 2 (ACE2). SPR-based competition analysis verified that both compounds blocked S-RBD and ACE2 binding, and SPR demonstrated that GA and MG bound to ACE2 (KD = 5.10 and 4.05 µM, respectively), suggesting that they blocked the receptor and neutralized SARS-CoV-2. Infection with SARS-CoV-2 pseudovirus showed that GA and MG suppressed viral entry into 293T-ACE2 cells. These S-RBD inhibitors have potential for drug design, while the findings provide a reference on HCZP composition and its use for treating COVID-19.

Small molecular weight epigenetic inhibitors modulate the extracellular matrix during pancreatic acinar ductal metaplasia.

The pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment is distinguished by a high degree of fibrosis and inflammation, known as desmoplasia. Desmoplasia increases the stromal deposition and extracellular matrix (ECM) stiffness observed in the tumor microenvironment, contributing to the dampened penetration of pharmacological agents. The molecular and biophysical composition of the ECM during the earliest cellular changes in the development of PDAC, i.e. acinar ductal metaplasia (ADM), has not been extensively explored. We report that the mRNA expression of key protein components of the ECM increases during ADM in p48Cre/+;LSL-KrasG12D (KC) mouse acinar organoids cultured in Matrigel. Treatment of the organoids with small molecular weight epigenetic modulating compounds that inhibit or reverse ADM (largazole, FK228 and chaetocin) dramatically reduced the tissue mRNA expression of collagens, hyaluronan synthase, laminin and fibronectin. The storage moduli, determined by video tracking of fluorescent nanoparticles embedded into the Matrigel, increased during ADM and was reduced following treatment with the epigenetic modulating compounds. We report that the ECM of mouse organoids stiffens during ADM and is further enhanced by the presence of mutant Kras. Moreover, select HDAC and HMT inhibitors reduced the mRNA expression of ECM components and ECM stiffness during inhibition and reversal of ADM, suggesting that these compounds may be useful as adjuvants to enhance the tumor penetration of agents used to treat PDAC.

Skeletal Editing of Aromatic N-Heterocycles via Hydroborative Cleavage of C-N Bonds - Scope, Mechanism, and Property.

Skeletal editing of the core structure of heterocycles offers new opportunities for chemical construction and is a promising yet challenging research topic that has recently gained increasing interest. However, several limitations of the reported systems remain to be addressed. For example, the reagents employed are generally in high-energy, such as chlorocarbene precursors, nitrene species, and metal carbenes, which are also associated with low atomic efficiencies. Thus, the development of simple systems for the skeletal editing of heterocycles is still desired. Herein, a straightforward and facile BH3-mediated skeletal editing of readily available indoles, benzimidazoles, and several other aromatic heterocycles is reported. Structurally diverse products were readily obtained, including tetrahydrobenzo azaborinines, diazaboroles, O-anilinophenylethyl alcohols, benzene-1,2-diamines, and more. Density functional theory (DFT) calculations and natural bond orbital (NBO) analysis revealed a BH3-induced C-N bond cleavage reaction pathway. An exciting and counterintuitive indole hydroboration phenomenon of -BH2 shift from C3-position to C2-position was disclosed. Moreover, the photophysical properties of the synthesized diazaboroles were studied, and an interestingly and pronounced aggregation-induced emission (AIE) behavior was disclosed.

3D printing materials and 3D printed surgical devices in oral and maxillofacial surgery: design, workflow and effectiveness.

Oral and maxillofacial surgery is a specialized surgical field devoted to diagnosing and managing conditions affecting the oral cavity, jaws, face and related structures. In recent years, the integration of 3D printing technology has revolutionized this field, offering a range of innovative surgical devices such as patient-specific implants, surgical guides, splints, bone models and regenerative scaffolds. In this comprehensive review, we primarily focus on examining the utility of 3D-printed surgical devices in the context of oral and maxillofacial surgery and evaluating their efficiency. Initially, we provide an insightful overview of commonly utilized 3D-printed surgical devices, discussing their innovations and clinical applications. Recognizing the pivotal role of materials, we give consideration to suitable biomaterials and printing technology of each device, while also introducing the emerging fields of regenerative scaffolds and bioprinting. Furthermore, we delve into the transformative impact of 3D-printed surgical devices within specific subdivisions of oral and maxillofacial surgery, placing particular emphasis on their rejuvenating effects in bone reconstruction, orthognathic surgery, temporomandibular joint treatment and other applications. Additionally, we elucidate how the integration of 3D printing technology has reshaped clinical workflows and influenced treatment outcomes in oral and maxillofacial surgery, providing updates on advancements in ensuring accuracy and cost-effectiveness in 3D printing-based procedures.

Unraveling non-radiative decay channels of exciplexes to construct efficient red emitters for organic light-emitting diodes.

Exciplex emitters naturally have thermally activated delayed fluorescence characteristics due to their spatially separated molecular orbitals. However, the intermolecular charge transfer potentially induces diverse non-radiative decay channels, severely hindering the construction of efficient red exciplexes. Thus, a thorough comprehension of this energy loss is of paramount importance. Herein, different factors, including molecular rigidity, donor-acceptor interactions and donor-donor/acceptor-acceptor interactions, that impact the non-radiative decay were systematically investigated using contrasting exciplex emitters. The exciplex with rigid components and intermolecular hydrogen bonds showed a photoluminescence quantum yield of 84.1% and a singlet non-radiative decay rate of 1.98 × 106 s-1 at an optimized mixing ratio, respectively, achieving a 3.3-fold increase and a 70% decrease compared to the comparison group. In the electroluminescent device, a maximum external quantum efficiency of 23.8% was achieved with an emission peak of 608 nm, which represents the state-of-the-art organic light-emitting diodes using exciplex emitters. Accordingly, a new strategy is finally proposed, exploiting system rigidification to construct efficient red exciplex emitters that suppress non-radiative decay.

Atroposelective Synthesis of Biaryl N-Oxides via Cu-Catalyzed De Novo Heteroaromatic N-Oxide Ring Formation.

Heteroaromatic N-oxides, renowned for their highly polar N─O bond and robust structure, exhibit significant bioactivities and have played a pivotal role in various drug development projects since the discovery of Minoxidil. Moreover, heteroaromatic N-oxides, featuring axially chiral biaryl frameworks, are indispensable as Lewis base catalysts and ligands in organic synthesis. Despite their importance, synthesizing these chiral compounds is challenging, necessitating chiral starting materials or resolution processes. Catalytic strategies rely on the functionalization of heteroaromatic N-oxide compounds, leading to products with a relatively limited skeletal diversity. This study introduces a Cu-catalyzed atroposelective method for synthesizing biaryl N-oxides via de novo heteroaromatic N-oxide ring formation. This mild and efficient approach achieves excellent stereoselectivities (up to 99:1 er), enabling the production of a wide array of N-oxides with novel heteroaromatic scaffolds. The axially chiral N-oxide product 3f demonstrates high stereoselectivity and recyclability as a Lewis base catalyst. Additionally, product 3e exhibits promising therapeutic efficacy against triple-negative breast cancer, with IC50 values of 4.8 and 5.2 µm in MDA-MB-231 and MDA-MB-468 cells, respectively. This research not only advances the synthesis of challenging chiral heteroaromatic N-oxides but also encourages further exploration of N-oxide entities in the discovery of bioactive small molecules.

Identification and validation of endoplasmic reticulum stress-related genes that enhance immunotherapy in colon cancer.

Background: Endoplasmic reticulum stress (ERS)-related genes are related to tumor growth, metastasis, and immunotherapy response. In this paper, we tried to identify ERS-related genes related to immunotherapy in colon cancer. Methods: ERS-related genes were downloaded from the Molecular Signatures Database (MSigDB) and GeneCards websites. Normal and tumor samples of the colon were obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), and Gene Expression Omnibus (GEO) databases. A risk model based on gene coefficients was constructed by using the least absolute shrinkage and selection operator (LASSO) regression. The inherent biological process differences between risk groups were explored by Gene Ontology (GO) and gene set enrichment analysis (GSEA). ESTIMATE and single-sample GSEA (ssGSEA) algorithms were used to analyze the correlation between tumor microenvironment (TME) and immune checkpoint and risk score. The semi-inhibitory concentration (IC50) values of chemotherapeutic drugs between risk groups were calculated to evaluate the sensitivity of immunotherapy. Results: The pathway analysis showed that the ERS risk model was relevant to biosynthesis and metabolism. Consistent clustering based on the ERS-related differentially expressed genes (DEGs) demonstrated that the samples divided into three clusters had significant clinicopathological differences. A risk model consisting of six ERS-related genes was established. The model was verified on GSE39582 and GSE17536 testing datasets. The results showed that ERS risk model was significantly related to TME and immune checkpoint, and these genes enhanced the immunotherapy ability of colon cancer. Conclusions: We established a risk model with ERS-related genes (PMM2, STC2, EIF2AK1, HSPA1A, SLC8A1, KCNQ1), which enhance the sensitivity of immunotherapy for colon cancer. These may provide a new perspective for the treatment of colon cancer.

Peptidomic analysis reveals novel peptide PDLC promotes cell proliferation in hepatocellular carcinoma via Ras/Raf/MEK/ERK pathway.

Hepatocellular carcinoma (HCC) still presents poor prognosis with low overall survival rates and limited therapeutic options available. Recently, attention has been drawn to peptidomic analysis, an emerging field of proteomics for the exploration of new potential peptide drugs for the treatment of various diseases. However, research on the potential function of HCC peptides is lacking. Here, we analyzed the peptide spectrum in HCC tissues using peptidomic techniques and explored the potentially beneficial peptides involved in HCC. Changes in peptide profiles in HCC were examined using liquid chromatography-mass spectrometry (LC-MS/MS). Analyze the physicochemical properties and function of differently expressed peptides using bioinformatics. The effect of candidate functional peptides on HCC cell growth and migration was evaluated using the CCK-8, colony formation, and transwell assays. Transcriptome sequencing analysis and western blot were employed to delve into the mode of action of potential peptide on HCC. Peptidomic analysis of HCC tissue yielded a total of 8683 peptides, of which 452 exhibited up-regulation and 362 showed down-regulation. The peptides that were differentially expressed, according to bioinformatic analysis, were closely linked to carbon metabolism and the mitochondrial inner membrane. The peptide functional validation identified a novel peptide, PDLC (peptide derived from liver cancer), which was found to dramatically boost HCC cell proliferation through the Ras/Raf/MEK/ERK signaling cascade. Our research defined the peptide's properties and pattern of expression in HCC and identified a novel peptide, PDLC, with a function in encouraging HCC progression, offering an entirely new potential therapeutic target the disease.

Exploring emission spatiotemporal pattern and potential reduction capacity in China's aviation sector: Flight trajectory optimization perspective.

China's rapid expansion of civil aviation has led to an increase in pollution-related issues, causing adverse health effects on populations near airports and downwind. Accurately quantifying aviation emissions is essential for effective emission management. Here, we developed a high-resolution aviation emissions inventory for China by employing a bottom-up approach that relied on daily flight schedules. By using the Aeronautical Information Publication (AIP) to reproduce real-world flight routes rather than conventional great-circle routes, we improved the accuracy of emissions and investigated the potential for reducing these emissions. Our findings demonstrated substantial variations in domestic civil aviation emissions both spatially and temporally. Emissions peaked in most provinces during Chinese holidays, particularly the Chinese Lunar New Year and summer holidays, highlighting the importance of detailed activity data for accurate emissions calculations. Therefore, we recommend extensive utilization of real-world flight routes, particularly in areas with limited Automatic Dependent Surveillance-Broadcast (ADS-B) coverage since they provide more accurate representations of actual flight trajectories. Our study also identified regions like Shaanxi, Sichuan, Beijing, and their surroundings having considerable potential for emission reduction due to substantial deviations from great-circle routes. This approach can enhance the accuracy and spatiotemporal resolution of aviation emissions at national and global scales throughout the year, without relying on extensive, long-term real-time flight trajectories. Additionally, it provides a unique way to quantify the potential for emission reductions across provinces in civil aviation, ultimately contributing to mitigating pollution-related health impacts from aviation emissions and promoting a more sustainable aviation industry.

Immunoprotective efficacy of 3 Klebsiella pneumoniae type I fimbriae proteins in a murine model.

Klebsiella pneumoniae is a primary cause of clinical mastitis in dairy cows, with prevention being crucial, as treatments often fail due to antimicrobial resistance. Recent studies identified type I fimbrial antigens of K. pneumoniae as promising vaccine candidates, but there are limited research data. In this study, 3 fimbriae genes (fimA, fimC and fimG) were cloned and recombinantly expressed in Escherichia coli and their protective efficacy against K. pneumoniae evaluated in a mouse model. All 3 recombinant fimbriae proteins elicited strong humoral immune responses in mice, significantly increasing IgG, IgG1 and IgG2a. Notably, using a model of mice challenged with an intraperitoneal injection of bacteria, FimG significantly reduced bacterial loads in the spleen and lung, whereas FimA and FimC had limited protection for these organs. Either active or passive immunization with FimG produced substantial protective effects in mice challenged with K. pneumoniae LD100; in contrast, the mortality rate in the FimA-immunized group was similar to that of the control group, whereas FimC had weak protection. We concluded that the FimG recombinant protein vaccine had a favorable protective effect, with potential for immunization against K. pneumoniae mastitis.

Evaluating deep learning techniques for identifying tongue features in subthreshold depression: a prospective observational study.

Objective: This study aims to evaluate the potential of using tongue image features as non-invasive biomarkers for diagnosing subthreshold depression and to assess the correlation between these features and acupuncture treatment outcomes using advanced deep learning models. Methods: We employed five advanced deep learning models-DenseNet169, MobileNetV3Small, SEResNet101, SqueezeNet, and VGG19_bn-to analyze tongue image features in individuals with subthreshold depression. These models were assessed based on accuracy, precision, recall, and F1 score. Additionally, we investigated the relationship between the best-performing model's predictions and the success of acupuncture treatment using Pearson's correlation coefficient. Results: Among the models, SEResNet101 emerged as the most effective, achieving an impressive 98.5% accuracy and an F1 score of 0.97. A significant positive correlation was found between its predictions and the alleviation of depressive symptoms following acupuncture (Pearson's correlation coefficient = 0.72, p<0.001). Conclusion: The findings suggest that the SEResNet101 model is highly accurate and reliable for identifying tongue image features in subthreshold depression. It also appears promising for assessing the impact of acupuncture treatment. This study contributes novel insights and approaches to the auxiliary diagnosis and treatment evaluation of subthreshold depression.

Long noncoding RNA NONHSAT122636.2 attenuates myocardial inflammation and apoptosis in myocarditis.

OBJECTIVE: The main pathological change of myocarditis is an inflammatory injury of cardiomyocytes. Long noncoding RNAs (lncRNAs) are closely related to inflammation, and our previous study showed that differential expression of lncRNAs is associated with myocarditis. This study aimed to investigate the impact of lncRNAs on the onset of myocarditis. METHODS: RNA expression was measured by quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Lipopolysaccharide (LPS) was used to induce inflammation in human cardiomyocytes (HCMs). The expression of inflammatory cytokines and myocardial injury markers was detected by enzyme-linked immunosorbent assay (ELISA) and RT-qPCR. Cell viability and apoptosis were measured by the cell counting kit-8 assay and flow cytometry. The binding force between lncRNA NONHSAT122636.2 and microRNA miRNA-2110 was detected using the dual-luciferase assay. RESULTS: NONHSAT122636.2 was dynamically expressed in patients with myocarditis and negatively correlated with inflammation severity. The overexpression of NONHSAT122636.2 improved inflammatory injury in LPS-stimulated HCMs. The study observed that there was a weak binding force between NONHSAT122636.2 and miR-2110. CONCLUSION: NONHSAT122636.2 attenuates myocardial inflammation and apoptosis in myocarditis. Additionally, its expression decreases in the peripheral blood of children suffering from myocarditis and in patients who are diagnosed for the first time showing higher diagnostic sensitivity and specificity. This decrease is negatively correlated with the degree of inflammation. Overall, the study suggests that NONHSAT122636.2 can be exploited as a potential diagnostic biomarker for pediatric myocarditis.

Inducing One-Step Dehydrogenation of Magnesium Borohydride via Confinement in Robust Dodecahedral Nitrogen-Doped Porous Carbon Scaffold.

A dodecahedral activated N-doped porous carbon scaffold is synthesized and used for the nanoconfinement of Mg(BH4)2. The optimized mesoporous scaffold possesses an accumulated pore width of 2.65 nm, high specific surface area (3955.9 m2 g-1), and large pore volume (2.15 cm3 g-1), providing ample space for the confinement of Mg(BH4)2 particles and numerous surface active sites for interactions with the same. The confined Mg(BH4)2 system features a dehydrogenation onset temperature of 81.5 °C, an extremely high capacity of 10.2 wt% H2, and an almost single-step dehydrogenation profile. Moreover, the system exhibits superior capacity retention of 82.7% after 20 cycles at a moderate temperature of 250 °C. Precise activation control enables a transformation from microporous carbon materials to mesoporous ones, and hence the efficient nanoconfinement of Mg(BH4)2 and realization of one-step dehydrogenation. The evolution of borohydride intermediates is systematically revealed throughout the cycling process. Density functional theory calculations demonstrate defective N heteroatoms within the scaffold are vital in reducing the strength of B─H bonds, and the N-doped carbon can facilitate decomposition of the irreversible MgB12H12 intermediate. This study opens up new avenues for designing robust carbon scaffolds doped with heteroatoms and analyzing intermediate evolution in nanoconfined Mg-based borohydride systems.

Thoracoscopic pulmonary resection combined with real-time image-guided percutaneous ablation for multiple pulmonary nodules: a novel surgical approach and literature review.

Background: Due to the widespread use of computed tomography (CT) screening and advances in diagnostic techniques, an increasing number of patients with multiple pulmonary nodules are being detected and pathologically diagnosed as synchronous multiple primary lung cancers (sMPLC). It has become a new challenge to treat multiple pulmonary nodules and obtain a favorable prognosis while minimizing the perioperative risk for patients. The purpose of this study was to summarize the preliminary experience with a hybrid surgery combining pulmonary resection and ablation for the treatment of sMPLC and to discuss the feasibility of this novel procedure with a literature review. Methods: This is a retrospective non-randomized controlled study. From January 1, 2022 to July 1, 2023, four patients underwent hybrid surgery combining thoracoscopic pulmonary resection and percutaneous pulmonary ablation for multiple pulmonary nodules. Patients were followed up at 3, 6 and 12 months postoperatively and the last follow-up was on November 30, 2023. Clinical characteristics, perioperative outcomes, pulmonary function recovery and oncologic prognosis were recorded. Meanwhile we did a literature review of studies on hybridized pulmonary surgery for the treatment of multiple pulmonary nodules. Results: All the four patients were female, aged 52 to 70 years, and had no severe cardiopulmonary dysfunction on preoperative examination. Hybrid surgery of simultaneous pulmonary resection and ablation were performed in these patients to treat 2 to 4 pulmonary nodules, assisted by intraoperative real-time guide of C-arm X-ray machine. The operation time was from 155 to 240 minutes, and intraoperative blood loss was from 50 to 200 mL. Postoperative hospital stay was 2 to 7 days, thoracic drainage duration was 2 to 6 days, and pleural drainage volume was 300-1,770 mL. One patient presented with a bronchopleural fistula due to pulmonary ablation; the fistula was identified and sutured during thoracoscopic surgery and the patient recovered well. No postoperative 90-day complications occurred. After 3 months postoperatively, performance status scores for these patients recovered to 80 to 100. No tumor recurrence or metastasis was detected during the follow-up period. Conclusions: Hybrid procedures combining minimally invasive pulmonary resection with ablation are particularly suitable for the simultaneous treatment of sMPLC. Patients had less loss of pulmonary function, fewer perioperative complications, and favorable oncologic prognosis. Hybrid surgery is expected to be a better treatment option for patients with sMPLC.

Network Pharmacology Combined with Bioinformatics Analysis to Texplore the Potential Mechanism of Phellodendri Chinensis Cortex Against Bladder Cancer.

The pharmacological mechanism of Phellodendri Chinensis cortex (PCC) against diseases, especially bladder cancer (BC), has never been reported systematically. This study was designed to explore potential mechanism of PCC in treatment of BC. First, we used network pharmacology to discover the potential mechanism of Phellodendri Chinensis cortex and phellodendrine against bladder cancer. Then, we used bioinformatics analysis to verify the correlation between gene expression analysis, survival analysis and common targets. Finally, molecular docking was used to calculate the binding energies of phellodendrine and common targets.A total of 264 targets for PCC were predicted, and 391 BC-related targets were obtained from 4 databases. There were 54 potential targets, 315 biological processes, and 120 signaling pathways involved for PCC against BC. The CDKN2A expression increased and the ESR1, JUN, IL6, AR, and PTGS2 levels decreased in BC according to Gene Expression Profiling Interactive Analysis version 2. The high expression of JUN, MYC, EGFR, and EGF and low expression of VEGFA and PPARG were associated with short overall survival (OS). The high expression of AKT1, EGFR, and EGF and low expression of IL1ß were associated with poor disease-free survival (DFS). The search of the intersection of phellodendrine and BC targets yielded 11 common targets, 50 biological processes, and 13 signaling pathways involved. High AURKA and FASN and low ESR1, JUN, ABCB1, and PTGS1 were expressed in BC. The high expression of FASN, ABCC1, PTGS1, JUN, and PIK3CA was associated with short OS, the high expression of PIK3CA and ABCC1 was associated with poor DFS prognosis. Phellodendrine showed a better binding affinity for PTGS2 protein with a docking score of -7.183 and a MM-GBSA result of -46.47 kcal/mol. This study revealed potential mechanism of PCC and phellodendrine against BC through network pharmacology and bioinformatics.

P/N-Type Conversion of 2D MoTe2 Controlled by Top Gate Engineering for Logic Circuits.

Two-dimensional (2D) transition-metal dichalcogenides (TMDCs) are regarded as promising materials for next-generation logic circuits. Top gate field-effect transistors (FETs) have independent gate control ability and can be fabricated directly on TMDC materials without a transfer process. Therefore, it has the merits of device reliability and complementary metal-oxide semiconductor (CMOS) process compatibility, which are demanded in practical circuit-level integration. However, the fabrication of the top gate FET involves depositing an insulating dielectric layer and a gate electrode in sequence on the TMDC channel material, which may affect the device performance. Insightfully investigating the influences of different top-gate-deposition methods on the electrical properties of the TMDC channel and further harnessing these influences to realize a homogeneous CMOS device on an identical 2D TMDC platform are with practice significance. In this work, p/n-type controllable top gate FET arrays based on 2H-MoTe2 are fabricated by using different top-gate-deposition methods. The electron-beam evaporation (EBE) of top metal gate exhibits an obvious n-doping effect on the 2H-MoTe2 channel and converts it from p-type to n-type, whereas the thermal evaporation of top gate affects little to the channel. High-resolution transmission electron microscopy (HR-TEM) analysis reveals that the high-energy metal atoms from the EBE process can penetrate through the 30 nm gate dielectric layers (including 10 nm Al2O3 seeding layer), leading to multiple atomic defects in both MoTe2 and the interface between MoTe2 and Al2O3. Furthermore, by utilizing the top gate engineering, a large-scale double-top-gate MoTe2 homogeneous CMOS inverter array is fabricated. The CMOS inverters exhibit clear logic swing, negligible hysteresis, and high device yield (∼93%), indicating high device reliability and stability. Notably, the fabrication process is facile, free from transfer procedure, and compatible with traditional silicon technology. This work promotes the application of 2D TMDCs in nanoelectronics integration.

A Patient With Proteinuria, Myalgias, and Decreased Pigmentation of Facial Skin.

A patient had bilateral leg edema, insomnia, myalgias, paresthesias in the fingertips, lighter pigmentation of the facial skin compared with other areas of the body, proteinuria, and an elevated creatinine level. What is the diagnosis and what would you do next?