CLDN6 inhibits breast cancer growth and metastasis through SREBP1-mediated RAS palmitoylation.

BACKGROUND: Breast cancer (BC) ranks as the third most fatal malignant tumor worldwide, with a strong reliance on fatty acid metabolism. CLDN6, a candidate BC suppressor gene, was previously identified as a regulator of fatty acid biosynthesis; however, the underlying mechanism remains elusive. In this research, we aim to clarify the specific mechanism through which CLDN6 modulates fatty acid anabolism and its impact on BC growth and metastasis. METHODS: Cell function assays, tumor xenograft mouse models, and lung metastasis mouse models were conducted to evaluate BC growth and metastasis. Human palmitic acid assay, triglyceride assay, Nile red staining, and oil red O staining were employed to investigate fatty acid anabolism. Reverse transcription polymerase chain reaction (RT-PCR), western blot, immunohistochemistry (IHC) assay, nuclear fractionation, immunofluorescence (IF), immunoprecipitation and acyl-biotin exchange (IP-ABE), chromatin immunoprecipitation (ChIP), dual luciferase reporter assay, and co-immunoprecipitation (Co-IP) were applied to elucidate the underlying molecular mechanism. Moreover, tissue microarrays of BC were analyzed to explore the clinical implications. RESULTS: We identified that CLDN6 inhibited BC growth and metastasis by impeding RAS palmitoylation both in vitro and in vivo. We proposed a unique theory suggesting that CLDN6 suppressed RAS palmitoylation through SREBP1-modulated de novo palmitic acid synthesis. Mechanistically, CLDN6 interacted with MAGI2 to prevent KLF5 from entering the nucleus, thereby restraining SREBF1 transcription. The downregulation of SREBP1 reduced de novo palmitic acid synthesis, hindering RAS palmitoylation and subsequent endosomal sorting complex required for transport (ESCRT)-mediated plasma membrane localization required for RAS oncogenic activation. Besides, targeting inhibition of RAS palmitoylation synergized with CLDN6 to repress BC progression. CONCLUSIONS: Our findings provide compelling evidence that CLDN6 suppresses the palmitic acid-induced RAS palmitoylation through the MAGI2/KLF5/SREBP1 axis, thereby impeding BC malignant progression. These results propose a new insight that monitoring CLDN6 expression alongside targeting inhibition of palmitic acid-mediated palmitoylation could be a viable strategy for treating oncogenic RAS-driven BC.

Promoting OH* adsorption by defect engineering of CuO catalysts for selective electro-oxidation of amines to nitriles coupled with hydrogen production.

Developing a high-efficiency benzylamine oxidation reaction (BOR) to replace the sluggish oxygen evolution reaction (OER) is an attractive pathway to promote H2 production and concurrently realize organic conversion. However, the electrochemical BOR performance is still far from satisfactory. Herein, we present a self-supported CuO nanorod array with abundant oxygen vacancies on copper foam (Vo-rich CuO/CF) as a promising anode for selective electro-oxidation of benzylamine (BA) to benzonitrile (BN) coupled with cathodic H2 generation. In situ infrared spectroscopy demonstrates the selective conversion of BA into BN on Vo-rich CuO. Furthermore, in situ Raman spectroscopy discloses a direct electro-oxidation mechanism of BA driven by electroactive hydroxyl species (OH*) over the Vo-rich CuO catalyst. Theoretical and experimental studies verify that the presence of oxygen vacancies is more favorable for the adsorption of OH* and BA molecules, enabling accelerated kinetics for the BOR. As expected, the Vo-rich CuO/CF electrode delivers outstanding BOR activity and stability, giving a high faradaic efficiency (FE) of over 93% for BN production at a potential of 0.40 V vs. Ag/AgCl. Impressively, almost 100% FE for H2 production can be further achieved at the NiSe cathode by integrating BA oxidation in a two-electrode electrolyzer.

Strain-dependent induction of primary bile acid 7-dehydroxylation by cholic acid.

BACKGROUND: Bile acids (BAs) are steroid-derived molecules with important roles in digestion, the maintenance of host metabolism, and immunomodulation. Primary BAs are synthesized by the host, while secondary BAs are produced by the gut microbiome through transformation of the former. The regulation of microbial production of secondary BAs is not well understood, particularly the production of 7-dehydroxylated BAs, which are the most potent agonists for host BA receptors. The 7-dehydroxylation of cholic acid (CA) is well established and is linked to the expression of a bile acid-inducible (bai) operon responsible for this process. However, little to no 7-dehydroxylation has been reported for other host-derived BAs (e.g., chenodeoxycholic acid, CDCA or ursodeoxycholic acid, UDCA). RESULTS: Here, we demonstrate that the 7-dehydroxylation of CDCA and UDCA by the human isolate Clostridium scindens is induced when CA is present, suggesting that CA-dependent transcriptional regulation is required for substantial 7-dehydroxylation of these primary BAs. This is supported by the finding that UDCA alone does not promote expression of bai genes. CDCA upregulates expression of the bai genes but the expression is greater when CA is present. In contrast, the murine isolate Extibacter muris exhibits a distinct response; CA did not induce significant 7-dehydroxylation of primary BAs, whereas BA 7-dehydroxylation was promoted upon addition of germ-free mouse cecal content in vitro. However, E. muris was found to 7-dehydroxylate in vivo. CONCLUSIONS: The distinct expression responses amongst strains indicate that bai genes are regulated differently. CA promoted bai operon gene expression and the 7-dehydroxylating activity in C. scindens strains. Conversely, the in vitro activity of E. muris was promoted only after the addition of cecal content and the isolate did not alter bai gene expression in response to CA. The accessory gene baiJ was only upregulated in the C. scindens ATCC 35704 strain, implying mechanistic differences amongst isolates. Interestingly, the human-derived C. scindens strains were also capable of 7-dehydroxylating murine bile acids (muricholic acids) to a limited extent. This study shows novel 7-dehydroxylation activity in vitro resulting from the presence of CA and suggests distinct bai gene expression across bacterial species.

RNA-seq revealed the protective effect of Huangqi Guizhi Wuwu Decoction against cisplatin induced PC12 cell injury.

BACKGROUND: Chemotherapy-induced peripheral neuropathy not only affects the tolerability of chemotherapy, but also causes intolerable and prolonged neuropathic pain in cancer patients. Currently, duloxetine is the only drug used to treat chemotherapy-induced peripheral neuropathy. However, the clinical use of this drug still faces several challenges. Therefore, we focused on traditional Chinese medicine to find an effective and safe alternative medicine. Huangqi Guizhi Wuwu Decoction is a traditional Chinese medicine that has been clinically used for treating nerve pain for thousands of years. This study aimed to investigate the neuroprotective effect of Huangqi Guizhi Wuwu Decoction on cisplatin-induced nerve injury in PC12 cells and to elucidate its potential mechanism of action. METHODS: Huangqi Guizhi Wuwu Decoction-containing serum and blank serum were prepared from a rat model. The protective effects of Huangqi Guizhi Wuwu Decoction on cisplatin (10 µmol/L)-induced PC12 cell injury were assessed by a Cell Counting Kit-8 assay. RNA expression in Huangqi Guizhi Wuwu Decoction-protected PC12 cells was analyzed using RNA-seq, and subsequently, differentially expressed genes were further analyzed using Gene Ontology and Gene Set Enrichment Analysis. RESULTS: The Cell Counting Kit-8 results showed that pretreatment of PC12 cells with Huangqi Guizhi Wuwu Decoction-containing serum (5%, 10%, 15%) significantly increased cells' viability to 10 µmol/L cisplatin-induced cell death. RNA-seq analysis revealed 843 differentially expressed genes in the chemotherapy-induced peripheral neuropathy group and 249 in the Huangqi Guizhi Wuwu Decoction group. The gene set enrichment analysis results in this study suggest that Huangqi Guizhi Wuwu Decoction may treat chemotherapy-induced peripheral neuropathy by enhancing axon guidance. CONCLUSIONS: This study provides valuable evidence for using Huangqi Guizhi Wuwu Decoction in treating chemotherapy-induced peripheral neuropathy, partially achieved by improving axon guidance pathways.

Up-regulation of IL-1ß and sPLA2-III in the medial prefrontal cortex contributes to orofacial and somatic hyperalgesia induced by malocclusion via glial-neuron crosstalk.

The medial prefrontal cortex (mPFC) has been identified as a key brain region involved in the modulation of chronic pain. Our recent study demonstrated that unilateral anterior crossbite (UAC) developed the comorbidity model of temporomandibular disorders (TMD) and fibromyalgia syndrome (FMS), which was characterized by both orofacial and somatic hyperalgesia. In the present study, UAC rats exhibited significant changes in gene expression in the mPFC. Enrichment analysis revealed that the significantly involved pathways were cytokines-cytokine receptor interaction and immune response. The expression of group III secretory phospholipase A2 (sPLA2-III) was significantly increased in the mPFC of UAC rats. Silencing sPLA2-III expression in the mPFC blocked the orofacial and somatic hyperalgesia. Immunofluorescence showed that sPLA2-III was mainly localized in neurons. The expression of interleukin-1ß (IL-1ß) in the mPFC significantly increased after UAC. Injection of IL-1ß antibody into the mPFC blocked orofacial and somatic hyperalgesia. IL-1ß was mainly localized in microglia cells. Furthermore, injection of IL-1ß antibody significantly reduced the expression of sPLA2-III. These results indicate that neuroinflammatory cascade responses induced by glial-neuron crosstalk in the mPFC may contribute to the development of TMD and FMS comorbidity, and IL-1ß and sPLA2-III are identified as novel potential therapeutic targets for the treatment of chronic pain in the comorbidity of TMD and FMS.

Trends and Patterns of HIV Transmitted Drug Resistance in China From 2018 to 2023.

BACKGROUND: National treatment guidelines of China evolving necessitates population-level surveillance of transmitted drug resistance (TDR) to inform or update HIV treatment strategies. METHODS: We analyzed the demographic, clinical, and virologic data obtained from people with HIV (PWH) residing in 31 provinces of China who were newly diagnosed between 2018 and 2023. Evidence of TDR was defined by the World Health Organization list for surveillance of drug resistance mutations. RESULTS: Among the 22 124 PWH with protease and reverse transcriptase sequences, 965 (4.36%; 95% CI, 4.1-4.63) had at least 1 TDR mutation. The most frequent TDR mutations were nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.39%; 95% CI, 2.19%-2.59%), followed by nucleoside reverse transcriptase inhibitor mutations(1.35%; 95% CI, 1.2%-1.5%) and protease inhibitor mutations (1.12%; 95% CI, .98%-1.26%). The overall protease and reverse transcriptase TDR increased significantly from 4.05% (95% CI, 3.61%-4.52%) in 2018 to 5.39% (95% CI, 4.33%-6.57%) in 2023. A low level of integrase strand transfer inhibitor TDR was detected in 9 (0.21%; 95% CI, .1%-.38%) of 4205 PWH. CONCLUSIONS: Presently, the continued use of NNRTI-based first-line antiretroviral therapy regimen for HIV treatment has been justified.

Improvement in the 95-95-95 Targets Is Accompanied by a Reduction in Both the Human Immunodeficiency Virus Transmission Rate and Incidence in China.

BACKGROUND: In 2016, China has implemented the World Health Organization's "treat all" policy. We aimed to assess the impact of significant improvements in the 95-95-95 targets on population-level human immunodeficiency virus (HIV) transmission dynamics and incidence. METHODS: We focused on 3 steps of the HIV care continuum: diagnosed, on antiretroviral therapy, and achieving viral suppression. The molecular transmission clusters were inferred using HIV-TRACE. New HIV infections were estimated using the incidence method in the European Centre for Disease Prevention and Control HIV Modelling Tool. RESULTS: Between 2004 and 2023, the national HIV epidemiology database recorded 2.99 billion person-times of HIV tests and identified 1 976 878 new diagnoses. We noted a roughly "inverted-V" curve in the clustering frequency, with the peak recorded in 2014 (67.1% [95% confidence interval, 63.7%-70.5%]), concurrent with a significant improvement in the 95-95-95 targets from 10-13-<71 in 2005 to 84-93-97 in 2022. Furthermore, we observed a parabolic curve for a new infection with the vertex occurring in 2010. CONCLUSIONS: In general, it was suggested that the improvements in the 95-95-95 targets were accompanied by a reduction in both the population-level HIV transmission rate and incidence. Thus, China should allocate more effort to the first "95" target to achieve a balanced 95-95-95 target.

Nuclear accumulation of rice UV-B photoreceptors is UV-B- and OsCOP1-independent for UV-B responses.

In plants, the conserved plant-specific photoreceptor UV RESISTANCE LOCUS 8 (UVR8) perceives ultraviolet-B (UV-B) light and mediates UV-B-induced photomorphogenesis and stress acclimation. In this study, we reveal that UV-B light treatment shortens seedlings, increases stem thickness, and enhances UV-B stress tolerance in rice (Oryza sativa) via its two UV-B photoreceptors OsUVR8a and OsUVR8b. Although the rice and Arabidopsis (Arabidopsis thaliana) UVR8 (AtUVR8) photoreceptors all form monomers in response to UV-B light, OsUVR8a, and OsUVR8b function is only partially conserved with respect to AtUVR8 in UV-B-induced photomorphogenesis and stress acclimation. UV-B light and CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) promote the nuclear accumulation of AtUVR8; by contrast, OsUVR8a and OsUVR8b constitutively localize to the nucleus via their own nuclear localization signals, independently of UV-B light and the RING-finger mutation of OsCOP1. We show that OsCOP1 negatively regulates UV-B responses, and shows weak interaction with OsUVR8s, which is ascribed to the N terminus of OsCOP1, which is conserved in several monocots. Furthermore, transcriptome analysis demonstrates that UV-B-responsive gene expression differs globally between Arabidopsis and rice, illuminating the evolutionary divergence of UV-B light signaling pathways between monocot and dicot plants.

Chronic stress induces wide-spread hyperalgesia: The involvement of spinal CCK1 receptors.

Chronic primary pain (CPP) occurs in the absence of tissue injury and includes temporomandibular disorders (TMD), fibromyalgia syndrome (FMS) and irritable bowel syndrome (IBS). CPP is commonly considered a stress-related chronic pain and often presents as wide-spread pain or comorbid pain conditions in different regions of the body. However, whether prolonged stress can directly result in the development of CPP comorbidity remains unclear. In the present study, we adapted a 21 day heterotypic stress paradigm in mice and examined whether chronic stress induced wide-spread hyperalgesia, modeling comorbid CPP in the clinic. We found that chronic stress induced anxiety- and depression-like behaviors, and resulted in long-lasting wide-spread hyperalgesia over several body regions such as the orofacial area, hindpaw, thigh, upper back and abdomen in female mice. We further found that the expression of cholecystokinin (CCK)1 receptors was significantly increased in the L4-L5 spinal dorsal horn of the female mice after 14 and 21 day heterotypic stress compared with the control animals. Intrathecal injection of the CCK1 receptor antagonist CR-1505 blocked pain hypersensitivity in the subcervical body including the upper back, thigh, hindpaw and abdomen. These findings suggest that the upregulation of spinal CCK1 receptors after chronic stress contributes to the central mechanisms underlying the development of wide-spread hyperalgesia, and may provide a potential and novel central target for clinical treatment of CPP.

Comprehensive biochemical analysis and nutritional evaluation of fatty acid and amino acid profiles in eight seahorse species (Hippocampus spp.).

Seahorses are increasingly recognized for their nutritional potential, which underscores the necessity for comprehensive biochemical analyses. This study aims to investigate the fatty acid and amino acid compositions of eight seahorse species, including both genders of Hippocampus trimaculatus, Hippocampus kelloggi, Hippocampus abdominalis, and Hippocampus erectus, to evaluate their nutritional value. We employed Gas Chromatography-Mass Spectrometry (GC-MS) and High-Performance Liquid Chromatography (HPLC) to analyze the fatty acid and amino acid profiles of the seahorse species. GC-MS was used to detect 34 fatty acid methyl esters, while HPLC provided detailed amino acid profiles. GC-MS analysis demonstrated high precision with relative standard deviations (RSDs) generally below 2.53 %, satisfactory repeatability (RSDs from 6.55 % to 8.73 %), and stability (RSDs below 2.82 %). Recovery rates for major fatty acids ranged from 98.73 % to 109.12 %. HPLC analysis showed strong separation of amino acid profiles with theoretical plate numbers exceeding 5000. Precision tests yielded RSDs below 1.23 %, with reproducibility and stability tests showing RSDs below 2.73 % and 2.86 %, respectively. Amino acid recovery rates ranged from 97.58 % to 104.66 %. Nutritional analysis revealed significant variations in fatty acid content among the species. Female H. erectus showed higher levels of hexadecanoic acid and saturated fatty acids, while male H. abdominalis had lower concentrations of n-3 full cis 4,7,10,13,16,19-docosahexaenoic acid (DHA). Total lipid yields varied from 3.2491 % to 12.3175 %, with major fatty acids constituting 17.9717 %-74.6962 % of total lipids. In conclusion, this study provides essential insights into the fatty acid and amino acid composition of seahorses, supporting their potential as valuable dietary supplements. The differences between genders in specific fatty acids suggest a nuanced nutritional profile that could be exploited for targeted dietary applications. Further research is needed to explore the seasonal and environmental variations affecting seahorse biochemical composition.

Toward better understanding and management of chemobrain: the potential utilities of the MemTrax memory test.

OBJECTIVE: To study the effects of chemotherapy on cognitive function in breast cancer patients, and to investigate the relationship of MemTrax test of memory and related functions to the FACT-Cog functional self-assessment for the evaluation and management of chemobrain. METHODS: In this prospective cohort study, clinical information of pathologically confirmed female breast cancer patients who decided to receive chemotherapy were collected in a questionnaire which was developed for this study and provided as a supplementary file. The FACT-Cog self-assessment and MemTrax test were administered before and after the chemotherapy treatments. Patients with chemobrain were identified using published criteria based on FACT-Cog scores, and MemTrax scores from chemobrain patients were analyzed. RESULTS: Fifty-six patients participated in this study, of which 41 participants completed 4 or more cycles of chemotherapy and were included in the final analyses here. Using the reported high end of minimal clinical differences (10.6 points) of FACT-Cog before and after chemotherapy, 18 patients suffered from chemobrain in this study. In these 18 chemobrain patients, no cognitive impairments were detected by MemTrax, which paradoxically demonstrated an improvement in the normal cognitive range. CONCLUSION: The cognitive impairment induced by chemotherapy in breast cancer patients is detectable by the FACT-Cog in a Chinese cohort but is not detected by the MemTrax memory test. The fact that the more objective MemTrax could not detect the impairment could alleviate patients' concerns which in turn would be beneficial for patients' mental health.

Fundamental Studies on Fluids-Independent Regenerative Nanocomposite Hydrogels for Fracture Treatments of Conformance Control.

Traditional granular hydrogels showed excellent injectivity, thermal integrity, and efficient remediation of heterogeneous reservoirs. However, granular hydrogels have demonstrated their inability to adapt to fractures due to the lack of sufficient interactions. Herein, we present new nanocomposite hydrogels consisting of cationic nanogelators and anionic granular hydrogels that can chemically in situ reform bulk hydrogels in the fractures. Interestingly, our granular hydrogels showed recross-linking independence on carrying fluids, contrary to prior reported fluid-dependent recross-linking granular hydrogels. The recross-linking of nanogelators and granular hydrogels can be accomplished from room temperature to 130 °C. The nanocomposite hydrogels displayed increased shear elastic moduli compared to pristine anionic granular hydrogels, probably due to the increased covalent cross-links formed by the homogeneous regenerative approach. We found that the granular hydrogels had high salinity tolerance even in the presence of 1000 ppm divalent ions of calcium (Ca2+) since Ca2+ ions often act as the cross-linker for partially hydrolyzed acrylamide-based hydrogels. Overall, we obtained new regenerative nanocomposite hydrogels based on cationic nanogelators and anionic granular hydrogels for fracture treatments.

Comparison efficacy and safety of total laparoscopic gastrectomy and laparoscopically assisted total gastrectomy in treatment of gastric cancer.

BACKGROUND: The development of laparoscopic technology has provided a new choice for surgery of gastric cancer (GC), but the advantages and disadvantages of laparoscopic total gastrectomy (LTG) and laparoscopic-assisted total gastrectomy (LATG) in treatment effect and safety are still controversial. The purpose of this study is to compare the efficacy and safety of the two methods in the treatment of GC, and to provide a basis for clinical decision-making. AIM: To compare the efficacy of totally LTG (TLTG) and LATG in the context of radical gastrectomy for GC. Additionally, we investigated the safety and feasibility of the total laparoscopic esophagojejunostomy technique. METHODS: Literature on comparative studies of the above two surgical methods for GC (TLTG group and LATG group) published before September 2022 were searched in the PubMed, Web of Science, Wanfang Database, CNKI, and other Chinese and English databases. In addition, the following search keywords were used: Gastric cancer, total gastrectomy, total laparoscopy, laparoscopy-assisted, esophagojejunal anastomosis, gastric/stomach cancer, total gastrectomy, totally/completely laparoscopic, laparoscopic assisted/laparoscopy assisted/laparoscopically assisted, and esophagojejunostomy/esophagojejunal anastomosis. Review Manager 5.3 software was used for the meta-analysis after two researchers independently screened the literature, extracted the data, and evaluated the risk of bias in the included studies. RESULTS: After layer-by-layer screening, 258 pieces of literature were recovered, and 11 of those pieces were eventually included. This resulted in a sample size of 2421 instances, with 1115 cases falling into the TLTG group and 1306 cases into the LATG group. Age or sex differences between the two groups were not statistically significant, according to the meta-analysis, however the average body mass index of the TLTG group was considerably higher than that of the LATG group (P = 0.01). Compared with those in the LATG group, the incision length in the TLTG group was significantly shorter (P < 0.001), the amount of intraoperative blood loss was significantly lower (P = 0.003), the number of lymph nodes removed was significantly greater (P = 0.04), and the time of first postoperative feeding and postoperative hospitalization were also significantly shorter (P = 0.03 and 0.02, respectively). There were no significant differences in tumor size, length of proximal incisal margin, total operation time, anastomotic time, postoperative pain score, postoperative anal exhaust time, postoperative anastomosis-related complications (including anastomotic fistula, anastomotic stenosis, and anastomotic hemorrhage), or overall postoperative complication rate (P > 0.05). CONCLUSION: TLTG and esophagojejunostomy are safe and feasible. Compared with LATG, TLTG has the advantages of less trauma, less bleeding, easier access to lymph nodes, and faster postoperative recovery, and TLTG is also suitable for obese patients.

Analysis of lymph node metastasis and survival prognosis in early gastric cancer patients: A retrospective study.

BACKGROUND: Early gastric cancer (EGC) is a common malignant tumor of the digestive system, and its lymph node metastasis and survival prognosis have been concerning. By retrospectively analyzing the clinical data of EGC patients, we can better understand the status of lymph node metastasis and its impact on survival and prognosis. AIM: To evaluate the prognosis of EGC patients and the factors that affect lymph node metastasis. METHODS: The clinicopathological data of 1011 patients with EGC admitted to our hospital between January 2015 and December 2023 were collected in a retrospective cohort study. There were 561 males and 450 females. The mean age was 58 ± 11 years. The patient underwent radical gastrectomy. The status of lymph node metastasis in each group was determined according to the pathological examination results of surgical specimens. The outcomes were as follows: (1) Lymph node metastasis in EGC patients; (2) Analysis of influencing factors of lymph node metastasis in EGC; and (3) Analysis of prognostic factors in patients with EGC. Normally distributed measurement data are expressed as mean ± SD, and a t test was used for comparisons between groups. The data are expressed as absolute numbers or percentages, and the chi-square test was used for comparisons between groups. Rank data were compared using a nonparametric rank sum test. A log-rank test and a logistic regression model were used for univariate analysis. A logistic stepwise regression model and a Cox stepwise regression model were used for multivariate analysis. The Kaplan-Meier method was used to calculate the survival rate and construct survival curves. A log-rank test was used for survival analysis. RESULTS: Analysis of influencing factors of lymph node metastasis in EGC. The results of the multifactor analysis showed that tumor length and diameter, tumor site, tumor invasion depth, vascular thrombus, and tumor differentiation degree were independent influencing factors for lymph node metastasis in patients with EGC (odds ratios = 1.80, 1.49, 2.65, 5.76, and 0.60; 95%CI: 1.29-2.50, 1.11-2.00, 1.81-3.88, 3.87-8.59, and 0.48-0.76, respectively; P < 0.05). Analysis of prognostic factors in patients with EGC. All 1011 patients with EGC were followed up for 43 (0-13) months. The 3-year overall survival rate was 97.32%. Multivariate analysis revealed that age > 60 years and lymph node metastasis were independent risk factors for prognosis in patients with EGC (hazard ratio = 9.50, 2.20; 95%CI: 3.31-27.29, 1.00-4.87; P < 0.05). Further analysis revealed that the 3-year overall survival rates of gastric cancer patients aged > 60 years and ≤ 60 years were 99.37% and 94.66%, respectively, and the difference was statistically significant (P < 0.05). The 3-year overall survival rates of patients with and without lymph node metastasis were 95.42% and 97.92%, respectively, and the difference was statistically significant (P < 0.05). CONCLUSION: The lymph node metastasis rate of EGC patients was 23.64%. Tumor length, tumor site, tumor infiltration depth, vascular cancer thrombin, and tumor differentiation degree were found to be independent factors affecting lymph node metastasis in EGC patients. Age > 60 years and lymph node metastasis are independent risk factors for EGC prognosis.

A targeting nanoplatform for chemo-photothermal synergistic therapy of small-cell lung cancer.

The precise delivery of drugs to tumor sites and the thermoresistance of tumors remain major challenges in photothermal therapy (PTT). Somatostatin receptor 2 (SSTR2) is proposed as an ideal target for the precise treatment of SCLC. We developed a targeting nano-drug delivery system comprising anti-SSTR2 monoclonal antibody (MAb) surface-modified nanoparticles co-encapsulating Cypate and gambogic acid (GA). The formed SGCPNs demonstrated excellent monodispersity, physiological stability, preferable biocompatibility, and resultant efficient photothermal conversion efficacy. SGCPNs were quickly internalized by SSTR2-overexpressing SCLC cells, triggering the release of GA under acidic and near-infrared (NIR) laser irradiation environments, leading to their escape from lysosomes to the cytosol and then diffusion into the nucleus. SGCPNs can not only decrease the cell survival rate but also inhibit the activity of heat shock protein 90 (HSP90). SGCPNs can be precisely delivered to xenograft tumors of SSTR2-positive SCLC in vivo. Upon NIR laser irradiation, therapy of SGCPNs showed significant tumor regression. In conclusion, SGCPNs provide a new chemo-photothermal synergistic treatment strategy for targeting SCLC.

Copper-Catalyzed Enantioselective Synthesis of Spirohydroindoles by Ethoxyformylmethylene Oxindole and Iminoester 1,3-Dipole Cycloaddition: An Examination of Associated Biological Activities.

A highly enantioselective 1,3-dipolar cycloaddition of ethoxyformylmethylene oxindole with iminoesters has been achieved using the Cu(I)-(S,Sp)-Ph Phosferrox catalytic system, generating a series of chiral spiro[pyrrolidin-3,3'-oxindole] compounds with four consecutive stereocenters, including a spirocycle quaternary center (71%-99% yield, up to >20:1 dr and 95:5 er). The compounds exhibited good inhibitory activity against Valsa mali (V.m.), Fusarium oxysporium (F.o.), and Alternaria brassicae (A.b.).

Aluminum scandium nitride on 8-inch Si wafers: material characterization and photonic device demonstration.

The anisotropic optical properties of aluminum scandium nitride (Al1-xScxN) thin films for both ordinary and extraordinary light are investigated. A quantitative analysis of the band structures of the wurtzite Al1-xScxN is carried out. In addition, Al1-xScxN photonic waveguides and bends are fabricated on 8-inch Si substrates. With x = 0.087 and 0.181, the light propagation losses are 5.98 ± 0.11 dB/cm and 8.23 ± 0.39 dB/cm, and the 90° bending losses are 0.05 dB/turn and 0.08 dB/turn at 1550 nm wavelength, respectively.

All-silicon metalens for broadband achromatic polarization multiplexing in long-wave infrared wavelengths.

Traditional long-wave infrared polarimetry usually relies on complex optical setups, making it challenging to meet the increasing demand for system miniaturization. To address this problem, we design an all-silicon broadband achromatic polarization-multiplexing metalens (BAPM) operating at the wavelength range of 9-12 µm. A machine-learning-based design method is developed to replace the tedious and computationally intensive simulation of a large number of meta-atoms. The results indicate that the coefficients of variation in focal length of the BAPM are 3.95% and 3.71%, and the average focusing efficiencies are 41.3% and 40.5% under broadband light incidence with x- and y-polarizations, respectively.

The impact of family factors and communication on recreational sedentary screen time among primary school-aged children: a cross-sectional study.

BACKGROUND: Childhood obesity is increasingly recognized as a major public health challenge worldwide, and excessive sedentary screen time is emerging as a key risk factor. This study aimed to assess the recreational screen sedentary time of Chinese primary school-aged children and investigate the relationship between screen-related family factors and the outcome variable. METHODS: Our study used data from a cross-sectional survey collected from fifth-grade students and their parents in Beijing, China, from April to May 2018 (n = 2,373). The questions included basic demographic information, family socioeconomic status, students' and parents' sedentary and exercising habits, within-family communicational factors, and health belief patterns. The recreational screen sedentary time of the children was compared across demographic groups. The study employed multivariate linear regression models to examine associations between children's screen time and various family factors, as well as the moderating effect of overall family communication. RESULTS: Our findings revealed an average daily recreational screen sedentary time of 2.4 h among participants. Screen time significantly varied across demographic categories, including children's sex, age, residence, parents' education, household income, family size, and primary family member. After adjustment, the proportion of child-owned digital devices (p < 0.01), child's personal room (p < 0.05), family screen-viewing together (p < 0.01), and parental screen time (p < 0.01) were positively related to children's recreational sedentary screen time. Parental restrictions on screen time (p < 0.001) and attitudes toward reducing sitting time (p < 0.01) were correlated with a decrease in children's screen time. The overall family communication environment significantly moderated the effects of parental practice of restricting children's screen time (p < 0.001), positive reinforcement by parents (p < 0.05), and parents' recreational sedentary screen time (p < 0.001). CONCLUSIONS: Our findings underscored the significance of family dynamics, parental practices, and communication in shaping children's screen time behaviors, providing valuable insights for tailored interventions and strategies to reduce childhood obesity.

Association of podocyte ultrastructural changes with proteinuria and pathological classification in type 2 diabetic nephropathy.

AIMS: Podocyte injury plays an essential role in the progression of diabetic nephropathy (DN). The associations between the ultrastructural changes of podocyte with proteinuria and the pathological classification of DN proposed by Renal Pathology Society (RPS) have not been clarified in patients with type 2 diabetic nephropathy (T2DN). METHODS: We collected 110 patients with kidney biopsy-confirmed T2DN at Peking University First Hospital from 2017 to 2022. The morphometric analysis on the podocyte foot process width (FPW) and podocyte detachment (PD) as markers of podocyte injury was performed, and the correlations between the ultrastructural changes of podocytes with severity of proteinuria and the RPS pathological classification of DN were analyzed. RESULTS: Mean FPW was significantly broader in the group of T2DN patients with nephrotic proteinuria (565.1 nm) than those with microalbuminuria (437.4 nm) or overt proteinuria (494.6 nm). The cut-off value of FPW (> 506 nm) could differentiate nephrotic proteinuria from non-nephrotic proteinuria with a sensitivity of 75.3% and a specificity of 75.8%. Percentage of PD was significantly higher in group of nephrotic proteinuria (3.2%) than that in microalbuminuria (0%) or overt proteinuria (0.2%). FPW and PD significantly correlated with proteinuria in T2DN (r = 0.473, p < 0.001 and r = 0.656, P < 0.001). FPW and PD correlated with RPS pathological classification of T2DN (r = 0.179, P = 0.014 and r = 0.250, P = 0.001). FPW value was increased significantly with more severe DN classification (P for trend =0.007). The percentage of PD tended to increase with more severe DN classification (P for trend = 0.017). CONCLUSIONS: Podocyte injury, characterized by FPW broadening and PD, was associated with the severity of proteinuria and the pathological classification of DN.