Long-term survivals of immune checkpoint inhibitors as neoadjuvant and adjuvant therapy in dMMR/MSI-H colorectal and gastric cancers.

BACKGROUND: The long-term survival benefit of immune checkpoint inhibitors (ICIs) in neoadjuvant and adjuvant settings is unclear for colorectal cancers (CRC) and gastric cancers (GC) with deficiency of mismatch repair (dMMR) or microsatellite instability-high (MSI-H). METHODS: This retrospective study enrolled patients with dMMR/MSI-H CRC and GC who received at least one dose of neoadjuvant ICIs (neoadjuvant cohort, NAC) or adjuvant ICIs (adjuvant cohort, AC) at 17 centers in China. Patients with stage IV disease were also eligible if all tumor lesions were radically resectable. RESULTS: In NAC (n = 124), objective response rates were 75.7% and 55.4%, respectively, in CRC and GC, and pathological complete response rates were 73.4% and 47.7%, respectively. The 3-year disease-free survival (DFS) and overall survival (OS) rates were 96% (95%CI 90-100%) and 100% for CRC (median follow-up [mFU] 29.4 months), respectively, and were 84% (72-96%) and 93% (85-100%) for GC (mFU 33.0 months), respectively. In AC (n = 48), the 3-year DFS and OS rates were 94% (84-100%) and 100% for CRC (mFU 35.5 months), respectively, and were 92% (82-100%) and 96% (88-100%) for GC (mFU 40.4 months), respectively. Among the seven patients with distant relapse, four received dual blockade of PD1 and CTLA4 combined with or without chemo- and targeted drugs, with three partial response and one progressive disease. CONCLUSION: With a relatively long follow-up, this study demonstrated that neoadjuvant and adjuvant ICIs might be both associated with promising DFS and OS in dMMR/MSI-H CRC and GC, which should be confirmed in further randomized clinical trials.

Resveratrol Alleviates Liver Fibrosis Induced by Long-Term Inorganic Mercury Exposure through Activating the Sirt1/PGC-1α Signaling Pathway.

Liver disease has become an important risk factor for global health. Resveratrol (Res) is a natural polyphenol which is widely found in foods and has a variety of biological activities. This study investigated the role of the microbiota-gut-liver axis in the Res relieving the liver fibrosis induced by inorganic mercury exposure. Twenty-eight mice were divided into four groups (n = 7) and treated with mercuric chloride and/or Res for 24 weeks, respectively. The results showed that Res mitigated the ileum injury induced by inorganic mercury and restrained LPS and alcohol entering the body circulation. Network pharmacological and molecular analyses showed that Res alleviated oxidative stress, metabolism disorders, inflammation, and hepatic stellate cell activation in the liver. In conclusion, Res alleviates liver fibrosis induced by inorganic mercury via activating the Sirt1/PGC-1α signaling pathway and regulating the microbial-gut-liver axis, particularly, increasing the relative enrichment of Bifidobacterium in the intestinal tract.

Obesity is associated with lower levels of negative emotions in polycystic ovary syndrome in clinical and animal studies.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders in women of reproductive age. It is frequently comorbid with obesity and negative emotions. Currently, there are few reports on the relationship between obesity and negative emotions in patients with PCOS. Here we performed both basic and clinical studies to study the relationship between obesity and negative emotions in PCOS. METHODS: We performed a cross-sectional study including 608 patients with PCOS and 184 healthy participants to assess the mental health status of people with different body mass indices (BMI). Self-rated anxiety, depression, and perceived stress scales were used for subjective mood evaluations. Rat PCOS models fed 45 and 60% high-fat diets were used to confirm the results of the clinical study. Elevated plus maze and open field tests were used to assess anxiety- and depression-like behaviors in rats. RESULTS: We observed overweight/obesity, increased depression, anxiety, and perceived stress in women with PCOS, and found that anxiety and depression were negatively correlated with BMI in patients with severe obesity and PCOS. Similar results were confirmed in the animal study; the elevated plus maze test and open field test demonstrated that only 60% of high fat diet-induced obesity partly reversed anxiety- and depression-like behaviors in PCOS rats. A high-fat diet also modulated rat hypothalamic and hippocampal luteinizing hormone and testosterone levels. CONCLUSION: These results reveal a potential relationship between obesity and negative emotions in PCOS and prompt further investigation. The interactions between various symptoms of PCOS may be targeted to improve the overall well-being of patients.

Obesity was negatively correlated with negative emotions in patients with PCOS.Obesity may affect the downregulation of LH and testosterone and participate in the regulation of emotions.Increased BMI may be beneficial for patients with PCOS in terms of the psychological aspects.

Progress of nanoparticle drug delivery system for the treatment of glioma.

Gliomas are typical malignant brain tumours affecting a wide population worldwide. Operation, as the common treatment for gliomas, is always accompanied by postoperative drug chemotherapy, but cannot cure patients. The main challenges are chemotherapeutic drugs have low blood-brain barrier passage rate and a lot of serious adverse effects, meanwhile, they have difficulty targeting glioma issues. Nowadays, the emergence of nanoparticles (NPs) drug delivery systems (NDDS) has provided a new promising approach for the treatment of gliomas owing to their excellent biodegradability, high stability, good biocompatibility, low toxicity, and minimal adverse effects. Herein, we reviewed the types and delivery mechanisms of NPs currently used in gliomas, including passive and active brain targeting drug delivery. In particular, we primarily focused on various hopeful types of NPs (such as liposome, chitosan, ferritin, graphene oxide, silica nanoparticle, nanogel, neutrophil, and adeno-associated virus), and discussed their advantages, disadvantages, and progress in preclinical trials. Moreover, we outlined the clinical trials of NPs applied in gliomas. According to this review, we provide an outlook of the prospects of NDDS for treating gliomas and summarise some methods that can enhance the targeting specificity and safety of NPs, like surface modification and conjugating ligands and peptides. Although there are still some limitations of these NPs, NDDS will offer the potential for curing glioma patients.

Freeze Metal Halide Perovskite for Dramatic Laser Tuning: Direct Observation via In Situ Cryo-Electron Microscope.

A frozen-temperature (below -28 °C) laser tuning way is developed to optimize metal halide perovskite (MHP)'s stability and opto-electronic properties, for emitter, photovoltaic and detector applications. Here freezing can adjust the competitive laser irradiation effects between damaging and annealing/repairing. And the ligand shells on MHP surface, which are widely present for many MHP materials, can be frozen and act as transparent solid templates for MHP's re-crystallization/re-growth during the laser tuning. With model samples of different types of CsPbBr3 nanocube arrays,an attempt is made to turn the dominant exposure facet from low-energy [100] facet to high-energy [111], [-211], [113] and [210] ones respectively; selectively removing the surface impurities and defects of CsPbBr3 nanocubes to enhance the irradiation durability by 101 times; and quickly (tens of seconds) modifying a Ruddlesden-Popper (RP) boundary into another type of boundary like twinning, and so on. The laser tuning mechanism is revealed by an innovative in situ cryo-transmission electron microscope (cryo-TEM) exploration at atomic resolution.

Locally advanced breast cancer patients should be cautious about the immediate breast reconstruction after mastectomy: a pooling analysis of safety and efficacy.

BACKGROUND: The purpose of this study was to compare safety and efficacy outcomes between immediate breast reconstruction (IBR) and mastectomy alone in locally advanced breast cancer patients. METHODS: We conducted a comprehensive literature search of PUBMED, EMBASE, and Cochrane databases. The primary outcomes evaluated were overall survival, disease-free survival, and local recurrence. The secondary outcome was the incidence of surgical complications. All data were analyzed using Review Manager 5.3. RESULTS: Sixteen studies, involving 15,364 participants were included in this meta-analysis. Pooled data demonstrated that patients underwent IBR were more likely to experience surgical complications than those underwent mastectomy alone (HR: 3.96, 95%CI [1.07,14.67], p = 0.04). No significant difference was found in overall survival (HR: 0.94, 95%CI [0.73,1.20], p = 0.62), disease-free survival (HR: 1.03, 95%CI [0.83,1.27], p = 0.81), or breast cancer specific survival (HR: 0.93, 95%CI [0.71,1.21], p = 0.57) between IBR group and Non-IBR group. CONCLUSIONS: Our study demonstrates that IBR after mastectomy does not affect the overall survival and disease-free survival of locally advanced breast cancer patients. However, IBR brings with it a nonnegligible higher risk of complications and needs to be fully evaluated and carefully decided.

CircRNA_101491 regulated the radiation sensitivity of esophageal squamous cell carcinomas via sponging miR-125a-5p.

BACKGROUND: At present, it has been found that many patients have acquired resistance to radiotherapy, which greatly reduces the effect of radiotherapy and further affects the prognosis. CircRNAs is involved in the regulation of radiosensitivity of many kinds of tumor cells. Therefore, the main purpose of this study is to explore the regulatory effect of CircRNA_101491 on radiosensitivity of ESCC and its related mechanism. METHODS: We established ESCC radiation-resistant cell line (KYSE150R cell) by gradient dose method, and tested the difference of KYSE150 between KYSE150R cell and parent cell in vitro. Then, after knocking down the expression of CircRNA_101491, a series of in vitro experiments were conducted to verify the effects of CircRNA_101491 on the phenotype and radiosensitivity of KYSE150R cells, and further analyzed the related regulatory mechanism. In addition, we also used the model of transplanted tumor in nude mice to investigate the effect of CircRNA_101491 on the radiosensitivity of ESCC in vivo. RESULTS: According to a series of in vitro experiments, we confirmed that KYSE150R cells lost the epithelial phenotype and obtained interstitial cell-like phenotype, and found that CircRNA_101491 was highly expressed in KYSE150R cells. In addition, we found that knocking down the expression of CircRNA_101491 will lift the inhibition of miR-125a-5p, and then reverse the process of EMT, accelerate the process of apoptosis, thus play a role in radiosensitization. The in vivo experiment of transplanted tumor in nude mice also showed that knocking down the expression of CircRNA_101491 could enhance the radiosensitivity of ESCC. CONCLUSION: In conclusion, we confirmed that interfering with the expression of CircRNA_101491 can relieve the inhibition of miR-125a-5p, thus reverse the process of interstitial phenotype, accelerate the process of apoptosis, and enhance the radiosensitivity of ESCC.

The Roles of Cytoplasmic Polyadenylation Element Binding Protein 1 in Tumorigenesis.

BACKGROUND: CPEB1 is an alternative polyadenylation binding protein that promotes or suppresses the expression of related mRNAs and proteins by binding to a highly conserved Cytoplasmic Polyadenylation Element (CPE) in the mRNAs 3'UTR. It is found to express abnormally in multiple tumors and affect tumorigenesis through many pathways. This review summarizes the functions and mechanisms of CPEB1 in a variety of cancers and suggests new directions for future related treatments. METHODS: A total of 95 articles were eligible for inclusion based on the year, quality of the research, and the strength of association with CPEB1. In this review, current research about how CPEB1 affects the initiation and progression of glioblastoma, breast cancer, hepatocellular carcinoma, gastric cancer, colorectal cancer, non-small cell lung cancer, prostate cancer, and melanoma are dissected, and the biomedical functions and mechanisms are summarized. RESULTS: CPEB1 mostly presents as a tumor suppressor for breast cancer, endometrial carcinoma, hepatocellular carcinoma, non-small cell lung cancer, prostate cancer, and melanoma. However, glioblastoma, gastric cancer, and colorectal cancer it exhibit two opposing properties of tumorigenesis, either promoting or inhibiting it. CONCLUSION: CPEB1 is likely to serve as a target and dynamic detection index or prognostic indicator for its function of apoptosis, activity, proliferation, migration, invasion, stemness, drug resistance, and even ferroptosis in various cancers.

Sappanone A ameliorated imiquimod-induced psoriasis-like dermatitis in BALB/c mice via suppressing Mmp8 expression and IL-17 signaling pathway.

Psoriasis is a prevalent immune-mediated inflammatory skin disease characterized by excessive abnormal proliferation of keratinocytes and infiltration of immune cells, which have significant impact on the life quality of individuals. Although biological agents and small molecule targeted drugs have brought significant clinical benefits to psoriasis patients, adverse reactions and high prices remains key issues in clinical medication of psoriasis, while natural product monomers possess high efficiency, low toxicity, anti-inflammatory and immunomodulatory properties, and bring new hope for the clinical treatment of psoriasis. Sappanone A (SA), a small molecule compound isolated from Caesalpinia sappan L, exhibits significant anti-inflammatory properties in various models, such as kidney inflammation and LPS-induced mice inflammation. Among these effects, the anti-inflammatory property of SA has received significant attention. In our study, we found that SA exhibited anti-proliferation and anti-inflammatory effects in HaCaT cells, and significantly alleviated imiquimod-induced psoriasis-like skin lesions via the inhibition of the excessive proliferation of keratinocytes and the infiltration of lymphocytes. Furthermore, the combinational analysis of network pharmacology and transcriptome sequencing revealed that SA exerted anti-psoriasis effects by inhibiting the matrix metalloproteinase 8 (Mmp8) expression and IL-17 pathway activation. In summary, we have first demonstrated that SA can be used as a novel anti-psoriasis drug, which may provide a novel strategy for the clinical treatment of psoriasis.

Moss differentiating the fluxes and sources of nitrogen deposition between 1984 and 2021 in a mountain area of Northern China.

Anthropogenic reactive nitrogen (N) deposition has increased significantly since the industrial revolution. Northern China has become a global hotspot for N deposition. However, few studies have been conducted to quantify the historical changes of atmospheric N deposition fluxes and source contributions in Northern China. By investigating N contents and δ15N values of mosses at Mount Tai (Northern China) in 1984 and 2021, we reconstructed fluxes and source contributions of wet inorganic N deposition and evaluated their historical changes. Compared with 1984, moss N contents (from 1.7 ± 0.3% to 2.1 ± 0.4%) showed a significant increase in 2021, which was mainly attributed to a significant increase in nitrate N deposition fluxes at Mount Tai. Moss δ15N values (from -5.9 ± 0.9‰ to -5.2 ± 2.4‰) showed a slight increase from 1984 to 2021 at Mount Tai. The importance of combustion-related NH3 (including vehicle exhaust, coal combustion, and biomass burning) in 2021 (51.2%) were higher than those in 1984 (43.9%), while the importance of volatilization NH3 sources (including waste and fertilizers) in 2021 (48.8%) were lower than those in 1984 (56.1%). It was fossil-fuel NOx (from vehicle exhaust and coal combustion) (54.1%) rather than non-fossil fuel NOx (from biomass burning and microbial N cycles) (45.9%) dominated NOx emissions in both 1984 and 2021. Our results revealed significant contributions of combustion-related NH3 and fossil-fuel NOx sources emissions to the elevation of N deposition at Mount Tai in Northern China, which are beneficial for mitigating N emissions and conducting ecological benefit assessments in Northern China.

GARNL3 identified as a crucial target for overcoming temozolomide resistance in EGFRvIII-positive glioblastoma.

OBJECT: Amplification of the epidermal growth factor receptor (EGFR) and its active mutant type III (EGFRvIII), frequently occurr in glioblastoma (GBM), contributing to chemotherapy and radiation resistance in GBM. Elucidating the underlying molecular mechanism of temozolomide (TMZ) resistance in EGFRvIII GBM could offer valuable insights for cancer treatment. METHODS: To elucidate the molecular mechanisms underlying EGFRvIII-mediated resistance to TMZ in GBM, we conducted a comprehensive analysis using Gene Expression Omnibus and The cancer genome atlas (TCGA) databases. Initially, we identified common significantly differentially expressed genes (DEGs) and prioritized those correlating significantly with patient prognosis as potential downstream targets of EGFRvIII and candidates for drug resistance. Additionally, we analyzed transcription factor expression changes and their correlation with candidate genes to elucidate transcriptional regulatory mechanisms. Using estimate method and databases such as Tumor IMmune Estimation Resource (TIMER) and CellMarker, we assessed immune cell infiltration in TMZ-resistant GBM and its relationship with candidate gene expression. In this study, we examined the expression differences of candidate genes in GBM cell lines following EGFRvIII intervention and in TMZ-resistant GBM cell lines. This preliminary investigation aimed to verify the regulatory impact of EGFRvIII on candidate targets and its potential involvement in TMZ resistance in GBM. RESULTS: Notably, GTPase Activating Rap/RanGAP Domain Like 3 (GARNL3) emerged as a key DEG associated with TMZ resistance and poor prognosis, with reduced expression correlating with altered immune cell profiles. Transcription factor analysis suggested Epiregulin (EREG) as a putative upstream regulator of GARNL3, linking it to EGFRvIII-mediated TMZ resistance. In vitro experiments confirmed EGFRvIII-mediated downregulation of GARNL3 and decreased TMZ sensitivity in GBM cell lines, further supported by reduced GARNL3 levels in TMZ-resistant GBM cells. CONCLUSION: GARNL3 downregulation in EGFRvIII-positive and TMZ-resistant GBM implicates its role in TMZ resistance, suggesting modulation of EREG/GARNL3 signaling as a potential therapeutic strategy.

Sex and ethnic disparities in hepatitis B evaluation and treatment across the world.

BACKGROUND & AIMS: Oral antiviral therapy with nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB) is well-tolerated and lifesaving, but real-world data on utilization are limited. We examined rates of evaluation and treatment in patients from the REAL-B consortium. METHODS: This was a cross-sectional study nested within our retrospective multinational clinical consortium (2000-2021). We determined the proportions of patients receiving adequate evaluation, meeting AASLD treatment criteria, and initiating treatment at any time during the study period. We also identified factors associated with receiving adequate evaluation and treatment using multivariable logistic regression analyses. RESULTS: We analyzed 12,566 adult treatment-naïve patients with CHB from 25 centers in 9 countries (mean age 47.1 years, 41.7% female, 96.1% Asian, 49.6% Western region, 8.7% cirrhosis). Overall, 73.3% (9,206 patients) received adequate evaluation. Among the adequately evaluated, 32.6% (3,001 patients) were treatment eligible by AASLD criteria, 83.3% (2,500 patients) of whom were initiated on NAs, with consistent findings in analyses using EASL criteria. On multivariable logistic regression adjusting for age, sex, cirrhosis, and ethnicity plus region, female sex was associated with adequate evaluation (adjusted odds ratio [aOR] 1.13, p = 0.004), but female treatment-eligible patients were about 50% less likely to initiate NAs (aOR 0.54, p <0.001). Additionally, the lowest evaluation and treatment rates were among Asian patients from the West, but no difference was observed between non-Asian patients and Asian patients from the East. Asian patients from the West (vs. East) were about 40-50% less likely to undergo adequate evaluation (aOR 0.60) and initiate NAs (aOR 0.54) (both p <0.001). CONCLUSIONS: Evaluation and treatment rates were suboptimal for patients with CHB in both the East and West, with significant sex and ethnic disparities. Improved linkage to care with linguistically competent and culturally sensitive approaches is needed. IMPACT AND IMPLICATIONS: Significant sex and ethnic disparities exist in hepatitis B evaluation and treatment, with female treatment-eligible patients about 50% less likely to receive antiviral treatment and Asian patients from Western regions also about 50% less likely to receive adequate evaluation or treatment compared to Asians from the East (there was no significant difference between Asian patients from the East and non-Asian patients). Improved linkage to care with linguistically competent and culturally sensitive approaches is needed.

Effect of biochar-derived DOM on contrasting redistribution of chromate during Schwertmannite dissolution and recrystallization.

Biochar-derived dissolved organic matter (BDOM), is extensively involved in the recrystallization of minerals and the speciation alteration of associated toxic metals. This study investigates how BDOM extracted from tobacco petiole (TP) or tobacco stalk (TS) biochar influences the speciation repartitioning of Cr(VI) in environments impacted by acid mine drainage (AMD), focusing on interactions with secondary minerals during Schwertmannite (Sch) dissolution and recrystallization. TP-BDOM, rich in lignin-like substances, slowed down the Cr-Sch dissolution and Cr release under acidic conditions compared to TS-BDOM. TP-BDOM's higher O/C component exerts a delayed impact on Cr-Sch stability and Cr(VI) reduction. In-situ ATR-FTIR and 2D-COS analysis showed that carboxylic and aromatic N-OH groups in BDOM could interact with Cr-Sch surfaces, affecting sulfate and Cr(VI) release. It was also observed that slight recrystallization occurred from Cr-Sch to goethite, along with increased Cr incorporation into secondary minerals within TS-BDOM. This enhances our understanding of BDOM's role in Cr(VI) speciation changes in AMD-contaminated sites.

The influencing mechanism of scenic spot online attention and tourists' purchase behavior: an AISAS model based investigation.

Introduction: In the era of the Internet, online digital traces have become a new way to study the online attention of scenic spots and tourists' purchase behavior. The public's information search on major search platforms is a series of manifestations of potential tourists' attention and interest in scenic spots, but there are few studies on how attention, interest and information search affect potential tourists to generate real purchase behavior. Method: This paper selects four dimensions of short video platform, travel website, search engine and social media to comprehensively measure the online attention of high-quality scenic spots in Yunnan Province, and then establishes a gray association analytic hierarchy process based on the relevant variables of the AISAS model to empirically analyze the primary and secondary factors affecting tourists' purchase behavior. Results: (1) From the perspective of the online attention of scenic spots on different platforms, the intensity of the public's scenic spots online attention on the four types of media platforms is in the order of travel websites, search engines, short videos and social media (2) From the perspective of spatial distribution characteristics, the online attention of high-quality scenic spots in Yunnan Province is unevenly distributed, that is, there is a big difference between the attention of higher star scenic spots and their star rating and popularity, while the attention of low-star scenic spots is not much different from their star rating and popularity (3) From the perspective of spatial agglomeration characteristics, the comprehensive online attention of high-quality scenic spots in Yunnan Province presents the spatial agglomeration characteristics of "the multi-core linkage of high-density in the east and north, and sub-high-density in the south" (4) The factors influencing the purchase behavior of potential tourists are sharing experience, attracting attention, generating interest and searching information. Discussion: By exploring the formation mechanism of high-quality scenic spots online attention in Yunnan Province and the mechanism of its spatial differentiation, this study not only enriches the logical chain of "tourism information source → potential tourists → demand driven → tourism information search → travel preference → destination selection → purchase decision → travel experience → real tourists → feelings after traveling → focus on feedback → tourism information source," but also broadens the application scenarios and application boundaries of travel preference theory and AISAS behavior model to a certain extent.

Sludge reduction and hydrogen production in a microbial photoelectrochemical cell with a g-C3N4/CQDs/BiOBr composite photocathode.

Hydrogen (H2) remains a pivotal clean energy source, and the emergence of Solar-powered Microbial Photoelectrochemical Cells (MPECs) presents promising avenues for H2 production while concurrently aiding organic matter degradation. This study introduces an MPEC system employing a g-C3N4/CQDs/BiOBr photocathode and a bioanode, successfully achieving simultaneous H2 production and sludge reduction. The research highlights the effective formation of a Z-type heterojunction in the g-C3N4/CQDs/BiOBr photocathode, substantially enhancing the photocurrent response under light conditions. Operating at - 0.4 V versus RHE, it demonstrated a current density of - 3.25 mA·cm-2, surpassing that of g-C3N4/BiOBr (-2.25 mA·cm-2) by 1.4 times and g-C3N4 (-2.04 mA·cm-2) by 1.6 times. When subjected to visible light irradiation and a 0.8 V applied bias voltage, the MPEC system achieved a current density of 1.0 mA·cm-2. The cumulative H2 production of the MPEC system reached 8.9 mL, averaging a production rate of 0.13 mL·h-1. In the anode chamber, the degradation rates of total chemical oxygen demand (TCOD), soluble chemical oxygen demand (SCOD), total suspended solids (TSS), volatile suspended solids (VSS), proteins, polysaccharides, and volatile fatty acids (VFA) in the sludge were recorded at 57.18%, 82.64%, 64.98%, 86.39%, 42.81%, 67.34%, and 29.01%, respectively.

An end-to-end method for predicting compound-protein interactions based on simplified homogeneous graph convolutional network and pre-trained language model.

Identification of interactions between chemical compounds and proteins is crucial for various applications, including drug discovery, target identification, network pharmacology, and elucidation of protein functions. Deep neural network-based approaches are becoming increasingly popular in efficiently identifying compound-protein interactions with high-throughput capabilities, narrowing down the scope of candidates for traditional labor-intensive, time-consuming and expensive experimental techniques. In this study, we proposed an end-to-end approach termed SPVec-SGCN-CPI, which utilized simplified graph convolutional network (SGCN) model with low-dimensional and continuous features generated from our previously developed model SPVec and graph topology information to predict compound-protein interactions. The SGCN technique, dividing the local neighborhood aggregation and nonlinearity layer-wise propagation steps, effectively aggregates K-order neighbor information while avoiding neighbor explosion and expediting training. The performance of the SPVec-SGCN-CPI method was assessed across three datasets and compared against four machine learning- and deep learning-based methods, as well as six state-of-the-art methods. Experimental results revealed that SPVec-SGCN-CPI outperformed all these competing methods, particularly excelling in unbalanced data scenarios. By propagating node features and topological information to the feature space, SPVec-SGCN-CPI effectively incorporates interactions between compounds and proteins, enabling the fusion of heterogeneity. Furthermore, our method scored all unlabeled data in ChEMBL, confirming the top five ranked compound-protein interactions through molecular docking and existing evidence. These findings suggest that our model can reliably uncover compound-protein interactions within unlabeled compound-protein pairs, carrying substantial implications for drug re-profiling and discovery. In summary, SPVec-SGCN demonstrates its efficacy in accurately predicting compound-protein interactions, showcasing potential to enhance target identification and streamline drug discovery processes.Scientific contributionsThe methodology presented in this work not only enables the comparatively accurate prediction of compound-protein interactions but also, for the first time, take sample imbalance which is very common in real world and computation efficiency into consideration simultaneously, accelerating the target identification and drug discovery process.

Tunable superconductivity in electron- and hole-doped Bernal bilayer graphene.

Graphene-based, high-quality, two-dimensional electronic systems have emerged as a highly tunable platform for studying superconductivity1-21. Specifically, superconductivity has been observed in both electron- and hole-doped twisted graphene moiré systems1-17, whereas in crystalline graphene systems, superconductivity has so far been observed only in hole-doped rhombohedral trilayer graphene (RTG)18 and hole-doped Bernal bilayer graphene (BBG)19-21. Recently, enhanced superconductivity has been demonstrated20,21 in BBG because of the proximity to a monolayer WSe2. Here we report the observation of superconductivity and a series of flavour-symmetry-breaking phases in electron- and hole-doped BBG/WSe2 devices by electrostatic doping. The strength of the observed superconductivity is tunable by applied vertical electric fields. The maximum Berezinskii-Kosterlitz-Thouless transition temperature for the electron- and hole-doped superconductivity is about 210 mK and 400 mK, respectively. Superconductivities emerge only when the applied electric fields drive the BBG electron or hole wavefunctions towards the WSe2 layer, underscoring the importance of the WSe2 layer in the observed superconductivity. The hole-doped superconductivity violates the Pauli paramagnetic limit, consistent with an Ising-like superconductor. By contrast, the electron-doped superconductivity obeys the Pauli limit, although the proximity-induced Ising spin-orbit coupling is also notable in the conduction band. Our findings highlight the rich physics associated with the conduction band in BBG, paving the way for further studies into the superconducting mechanisms of crystalline graphene and the development of superconductor devices based on BBG.

Examining network structure of impulsivity and depression in adolescents and young adults: A two-sample study.

BACKGROUND: Depression ranks as one of the top five contributors to ill health in youth, the most formative period in life. Extensive research has highlighted the significant role of impulsivity in understanding depression. However, there has been limited exploration into how each dimension of impulsivity uniquely affect depressive symptoms, especially across crucial developmental stages like adolescence and young adulthood. METHODS: This study investigates the unique relationships between impulsivity (assessed by the short UPPS-P scale) and depression (assessed by the Patient Health Questionnaire-9) via network analysis. We analysed data from a total of 2296 participants, comprising 858 adolescents aged 14-17 years and 1438 young adults aged 18-25 years, to estimate both a combined network and age-group specific networks. Key features of the networks, including their structure, global connectivity, and bridge nodes, were compared. RESULTS: The results indicated that age differentially impacts individual depression symptoms, both directly and indirectly, via impulsivity dimensions. The comparison test revealed consistent network structures between the two age groups, with several robust pathways, such as lack of perseverance to concentration difficulties, sensation seeking to suicidal ideation, and negative urgency to feelings of worthlessness. Negative urgency and lack of perseverance were identified as bridge nodes across the two networks. LIMITATIONS: The study employed a cross-sectional design, which limits the ability to estimate causal or temporal relationships. CONCLUSIONS: The current findings highlight the significance of tailoring intervention strategies to individual symptom profiles and assessing negative urgency and lack of perseverance as potential early targets for depression among youth.

Population interaction network in representative gravitational search algorithms: Logistic distribution leads to worse performance.

In this paper, a novel study on the way inter-individual information interacts in meta-heuristic algorithms (MHAs) is carried out using a scheme known as population interaction networks (PIN). Specifically, three representative MHAs, including the differential evolutionary algorithm (DE), the particle swarm optimization algorithm (PSO), the gravitational search algorithm (GSA), and four classical variations of the gravitational search algorithm, are analyzed in terms of inter-individual information interactions and the differences in the performance of each of the algorithms on IEEE Congress on Evolutionary Computation 2017 benchmark functions. The cumulative distribution function (CDF) of the node degree obtained by the algorithm on the benchmark function is fitted to the seven distribution models by using PIN. The results show that among the seven compared algorithms, the more powerful DE is more skewed towards the Poisson distribution, and the weaker PSO, GSA, and GSA variants are more skewed towards the Logistic distribution. The more deviation from Logistic distribution GSA variants conform, the stronger their performance. From the point of view of the CDF, deviating from the Logistic distribution facilitates the improvement of the GSA. Our findings suggest that the population interaction network is a powerful tool for characterizing and comparing the performance of different MHAs in a more comprehensive and meaningful way.

Tailoring d-p Orbital Hybridization to Decipher the Essential Effects of Heteroatom Substitution on Redox Kinetics.

The heteroatom substitution is considered as a promising strategy for boosting the redox kinetics of transition metal compounds in hybrid supercapacitors (HSCs) although the dissimilar metal identification and essential mechanism that dominate the kinetics remain unclear. It is presented that d-p orbital hybridization between the metal and electrolyte ions can be utilized as a descriptor for understanding the redox kinetics. Herein, a series of Co, Fe and Cu heteroatoms are respectively introduced into Ni3Se4 cathodes, among them, only the moderate Co-substituted Ni3Se4 can hold the optimal d-p orbital hybridization resulted from the formed more unoccupied antibonding states π*. It inevitably enhances the interfacial charge transfer and ensures the balanced OH- adsorption-desorption to accelerate the redox kinetics validated by the lowest reaction barrier (0.59 eV, matching well with the theoretical calculations. Coupling with the lower OH- diffusion energy barrier, the prepared cathode delivers ultrahigh rate capability (~68.7% capacity retention even the current density increases by 200 times), and an assembled HSC also presents high energy/power density. This work establishes the principles for determining heteroatoms and deciphers the underlying effects of the heteroatom substitution on improving redox kinetics and the rate performance of battery-type electrodes from a novel perspective of orbital-scale manipulation.