Trends in cancer-related suicide in the United States: a population-based epidemiology study spanning 40 years of data.

Large cohort studies examining trends in cancer-related suicide are lacking. We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database, encompassing a total of 4,870,410 patients diagnosed with cancer from 1975 to 2017 in the United States. Joinpoint regression was used to estimate the annual percent change (APC) and average annual percentage change (AAPC) of age-adjusted rates of suicide. In the past 40 years, we revealed a gradual increase in cancer-related suicide rates from 1975 to 1989, followed by a gradual decrease from 1989 to 2013, and a marked decrease from 2013 to 2017. These trends suggested the potential impact of advancements in psychosocial care for patients with cancer in contributing to the observed decrease in suicide rates.

Retrosynthesis Zero: Self-Improving Global Synthesis Planning Using Reinforcement Learning.

The field of computer-aided synthesis planning (CASP) has witnessed significant growth in recent years. Still, many CASP programs rely on large data sets to train neural networks, resulting in limitations due to the data quality and prior knowledge from chemists. In response, we propose Retrosynthesis Zero (ReSynZ), a reaction template-based method that combines Monte Carlo Tree Search with reinforcement learning inspired by AlphaGo Zero. Unlike other single-step reaction template-based CASP methods, ReSynZ takes complete synthesis paths for complex molecules, determined by reaction rules, as input for training the neural network. ReSynZ enables neural networks trained with relatively small reaction data sets (tens of thousands of data) to generate multiple synthesis pathways for a target molecule and suggest possible reaction conditions. On multiple data sets of molecular retrosynthesis, ReSynZ demonstrates excellent predictive performance compared to existing algorithms. The advantages, such as self-improving model features, flexible reward settings, the potential to surpass human limitations in chemical synthesis route planning, and others, make ReSynZ a valuable tool in chemical synthesis design.

Sign language recognition based on dual-path background erasure convolutional neural network.

Sign language is an important way to provide expression information to people with hearing and speaking disabilities. Therefore, sign language recognition has always been a very important research topic. However, many sign language recognition systems currently require complex deep models and rely on expensive sensors, which limits the application scenarios of sign language recognition. To address this issue, based on computer vision, this study proposed a lightweight, dual-path background erasing deep convolutional neural network (DPCNN) model for sign language recognition. The DPCNN consists of two paths. One path is used to learn the overall features, while the other path learns the background features. The background features are gradually subtracted from the overall features to obtain an effective representation of hand features. Then, these features are flatten into a one-dimensional layer, and pass through a fully connected layer with an output unit of 128. Finally, use a fully connected layer with an output unit of 24 as the output layer. Based on the ASL Finger Spelling dataset, the total accuracy and Macro-F1 scores of the proposed method is 99.52% and 0.997, respectively. More importantly, the proposed method can be applied to small terminals, thereby improving the application scenarios of sign language recognition. Through experimental comparison, the dual path background erasure network model proposed in this paper has better generalization ability.

Large-Area Near-Infrared Emission Enhancement on Single Upconversion Nanoparticles by Metal Nanohole Array.

Single lanthanide (Ln) ion doped upconversion nanoparticles (UCNPs) exhibit great potential for biomolecule sensing and counting. Plasmonic structures can improve the emission efficiency of single UCNPs by modulating the energy transferring process. Yet, achieving robust and large-area single UCNP emission modulation remains a challenge, which obstructs investigation and application of single UCNPs. Here, we present a strategy using metal nanohole arrays (NHAs) to achieve energy-transfer modulation on single UCNPs simultaneously within large-area plasmonic structures. By coupling surface plasmon polaritons (SPPs) with higher-intermediate state (1D2 → 3F3, 1D2 → 3H4) transitions, we achieved a remarkable up to 10-fold enhancement in 800 nm emission, surpassing the conventional approach of coupling SPPs with an intermediate ground state (3H4 → 3H6). We numerically simulate the electrical field distribution and reveal that luminescent enhancement is robust and insensitive to the exact location of particles. It is anticipated that the strategy provides a platform for widely exploring applications in single-particle quantitative biosensing.

Computation-Driven Rational Design of Self-Assembled Short Peptides for Catalytic Hydrogen Production.

Self-assembling peptides represent a captivating area of study in nanotechnology and biomaterials. This interest is largely driven by their unique properties and the vast application potential across various fields such as catalytic functions. However, design complexities, including high-dimensional sequence space and structural diversity, pose significant challenges in the study of such systems. In this work, we explored the possibility of self-assembled peptides to catalyze the hydrolysis of hydrosilane for hydrogen production using ab initio calculations and carried out wet-lab experiments to confirm the feasibility of these catalytic reactions under ambient conditions. Further, we delved into the nuanced interplay between sequence, structural conformation, and catalytic activity by combining modeling with experimental techniques such as transmission electron microscopy and nuclear magnetic resonance and proposed a dual mode of the microstructure of the catalytic center. Our results reveal that although research in this area is still at an early stage, the development of self-assembled peptide catalysts for hydrogen production has the potential to provide a more sustainable and efficient alternative to conventional hydrogen production methods. In addition, this work also demonstrates that a computation-driven rational design supplemented by experimental validation is an effective protocol for conducting research on functional self-assembled peptides.

A Radiological-Radiomics model for differentiation between minimally invasive adenocarcinoma and invasive adenocarcinoma less than or equal to 3 cm: A two-center retrospective study.

OBJECTIVE: To develop a Radiological-Radiomics (R-R) combined model for differentiation between minimal invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IA) of lung adenocarcinoma (LUAD) and evaluate its predictive performance. METHODS: The clinical, pathological, and imaging data of a total of 509 patients (522 lesions) with LUAD diagnosed by surgical pathology from 2 medical centres were retrospectively collected, with 392 patients (402 lesions) from center 1 trained and validated using a five-fold cross-validation method, and 117 patients (120 lesions) from center 2 serving as an independent external test set. The least absolute shrinkage and selection operator (LASSO) method was utilized to filter features. Logistic regression was used to construct three models for predicting IA, namely, Radiological model, Radiomics model, and R-R model. Also, receiver operating curve curves (ROCs) were plotted, generating corresponding area under the curve (AUC), sensitivity, specificity, and accuracy. RESULTS: The R-R model for IA prediction achieved an AUC of 0.918 (95 % CI: 0.889-0.947), a sensitivity of 80.3 %, a specificity of 88.2 %, and an accuracy of 82.1 % in the training set. In the validation set, this model exhibited an AUC of 0.906 (95 % CI: 0.842-0.970), a sensitivity of 79.9 %, a specificity of 88.1 %, and an accuracy of 81.8 %. In the external test set, the AUC was 0.894 (95 % CI: 0.824-0.964), a sensitivity of 84.8 %, a specificity of 78.6 %, and an accuracy of 83.3 %. CONCLUSION: The R-R model showed excellent diagnostic performance in differentiating MIA and IA, which can provide a certain reference for clinical diagnosis and surgical treatment plans.

A frontier exploration of ancient craftsmanship: Effects of various tea products in traditional Chinese cuisine "tea flavored beef".

Modern science often overlooks to reveal the scientific essence of traditional crafts to promote their inheritance and development. In this work, five different types of tea products were prepared using the same variety of tea leaves referring to traditional methods. The analysis of their components and activities indicated that the processing reduced total catechin contents (from 172.8 mg/g to 48.2 mg/g) and promoted the synthesis of theaflavins (from 17.9 mg/g to 43.4 mg/g), reducing antioxidant and antimicrobial abilities of the resulting tea products. On this basis, the tea products were applied to "tea flavored beef" to reveal long-term effects. Within 15 days of storage, tea treatment showed remarkable antimicrobial and antioxidant activities on the beef. Also, the declines of sensory scores and texture of the treated beef were significantly suppressed. Meanwhile, protein degradation in the beef was inhibited, limiting the contents of various biogenic amines within relatively low levels.

Simulating chemical reactions promoted by self-assembled peptides with catalytic properties.

Peptides that self-assemble exhibit distinct three-dimensional structures and attributes, positioning them as promising candidates for biocatalysts. Exploring their catalytic processes enhances our comprehension of the catalytic actions inherent to self-assembling peptides, laying a theoretical foundation for creating novel biocatalysts. The investigation into the intricate reaction mechanisms of these entities is rendered challenging due to the vast variability in peptide sequences, their aggregated formations, supportive elements, structures of active sites, types of catalytic reactions, and the interplay between these variables. This complexity hampers the elucidation of the linkage between sequence, structure, and catalytic efficiency in self-assembling peptide catalysts. This chapter delves into the latest progress in understanding the mechanisms behind peptide self-assembly, serving as a catalyst in hydrolysis and oxidation reactions, and employing computational analyses. It discusses the establishment of models, selection of computational strategies, and analysis of computational procedures, emphasizing the application of modeling techniques in probing the catalytic mechanisms of peptide self-assemblies. It also looks ahead to the potential future trajectories within this research domain. Despite facing numerous obstacles, a thorough investigation into the structural and catalytic mechanisms of peptide self-assemblies, combined with the ongoing advancement in computational simulations and experimental methodologies, is set to offer valuable theoretical insights for the development of new biocatalysts, thereby significantly advancing the biocatalysis field.

Recent advances in potential therapeutic targets of ferroptosis­associated pathways for the treatment of stroke (Review).

Stroke is a severe neurological disease that is associated with high rates of morbidity and mortality, and the underlying pathological processes are complex. Ferroptosis fulfills a significant role in the progression and treatment of stroke. It is well established that ferroptosis is a type of programmed cell death that is distinct from other forms or types of cell death. The process of ferroptosis involves multiple signaling pathways and regulatory mechanisms that interact with mechanisms inherent to stroke development. Inducers and inhibitors of ferroptosis have been shown to exert a role in the onset of this cell death process. Furthermore, it has been shown that interfering with ferroptosis affects the occurrence of stroke, indicating that targeting ferroptosis may offer a promising therapeutic approach for treating patients of stroke. Hence, the present review aimed to summarize the latest progress that has been made in terms of using therapeutic interventions for ferroptosis as treatment targets in cases of stroke. It provides an overview of the relevant pathways and molecular mechanisms that have been investigated in recent years, highlighting the roles of inducers and inhibitors of ferroptosis in stroke. Additionally, the intervention potential of various types of Traditional Chinese Medicine is also summarized. In conclusion, the present review provides a comprehensive overview of the potential therapeutic targets afforded by ferroptosis­associated pathways in stroke, offering new insights into how ferroptosis may be exploited in the treatment of stroke.

Intermittent hyperglycaemia induces macrophage dysfunction by extracellular regulated protein kinase-dependent PKM2 translocation in periodontitis.

Early fluctuations in blood glucose levels increased susceptibility to macrophage dysfunction. However, the underlying pathological mechanisms linking glucose variations and macrophage dysregulation remains elusive. In current study, we established an animal model of transient intermittent hyperglycaemia (TIH) to simulate early fluctuations in blood glucose levels. Our findings revealed that both TIH and diabetic group exhibited more severe periodontal lesions and increased secretion of pro-inflammatory cytokines compared to healthy controls. In immortalized bone marrow-derived macrophages (iBMDMs), phagocytosis and chemotaxis were impaired with transient and lasting hyperglycaemia, accompanied by enhanced glycolysis. We also found that TIH activated pyruvate kinase M2 (PKM2) through the phosphorylation of extracellular regulated protein kinase (ERK) in vivo, particularly at dimeric levels. In macrophage cultured with TIH, PKM2 translocated into the nucleus and involved in the regulating inflammatory genes, including TNF-α, IL-6 and IL-1ß. PKM2 translocation and secretion of inflammatory cytokines were attenuated by PD98059, while PKM2 tetramer activator TEPP-46 prevented the formation of dimeric PKM2 in macrophages. Moreover, inhibition of glycolysis alleviated the TIH-induced pro-inflammatory cytokines. In conclusion, our manuscript provides a rationale for understanding how TIH modulates metabolic rewiring and dysfunction in macrophages via ERK-dependent PKM2 nuclear translocation.

Unraveling the relationships between processing conditions and PhIP formation in chemical model system and roast pork patty via principal component analysis.

2-amino-1-methyl-6-phenylimidazole [4,5-b] pyridine (PhIP) is one of the higher levels of HAAs produced in protein foods during heating. The effects of heating temperature, time, and concentration of precursors on PhIP and related substances in the chemical model system and roast pork patty were studied using HPLC-Q-Orbitrap-HRMS and GC-MS. Results showed that the heating temperature, time, and concentration of four precursors significantly affected PhIP and its related substances (P < 0.05) in the chemical model system. Among them, PhIP production was greatest when heating at 200 min with 220 °C, and the concentrations of phenylalanine, creatinine, glucose, and creatine added were 10, 20, 20, and 20 mmol/L, respectively. Moreover, as the fat proportion of roast pork patties increased, PhIP and its intermediate-phenylacetaldehyde concentrations increased substantially (P < 0.05). PCA results showed that the samples of PhIP and related substances gradually dispersed as the temperature and time increased, and there were obvious effects among them.

Chemical Constituents from the deep-sea-derived Fungus Aureobasidium melanogenum LUO5.

Three new C10 and C12 aliphatic δ-lactones (1-3), three new fatty acid methyl esters (4-6), and eight known compounds (7-14) were isolated from the marine Aureobasidium sp. LUO5. Their structures were established by detailed analyses of the NMR, HRESIMS, optical rotation, and ECD data. All isolates were tested for their inhibitory effects on nitric oxide production in LPS-induced BV-2 cells. Notably, compound 4 displayed the strongest inhibitory effect with the IC50 value of 120.3 nM.

Neuroprotective effects of intermittent fasting in the aging brain.

BACKGROUND: A major risk factor for neurodegenerative disorders is old age. Nutritional interventions that delay aging, such as calorie restriction (CR) and intermittent fasting (IF), as well as pharmaceuticals that affect the pathways linking nutrition and aging processes, have been developed in recent decades and have been shown to alleviate the effects of aging on the brain. SUMMARY: CR is accomplished by alternating periods of ad libitum feeding and fasting. In animal models, IF has been shown to increase lifespan and slow the progression and severity of age-related pathologies such as cardiovascular and neurodegenerative diseases and cancer. According to recent research, dietary changes can help older people with dementia retain brain function. However, the mechanisms underlying the neuroprotective effect of IF on the aging brain and related questions in this area of study (i.e., the potential of IF to treat neurodegenerative disorders) remain to be examined. KEY MESSAGES: This review addresses the hypothesis that IF may have translational potential in protecting the aged brain while summarizing the research supporting the putative neuroprotective mechanisms of IF in animal models. Additionally, given the emerging understanding of the connection between aging and dementia, our investigations may offer a fresh perspective on the use of dietary interventions for enhancing brain function and preventing dementia in elderly individuals. Finally, the absence of guidelines regarding the application of IF in patients hampers its broad utilization in clinical practice, and further studies are needed to improve our knowledge of the long-term effects of IF on dementia before it can be widely prescribed. In conclusion, IF may be an ancillary intervention for preserving memory and cognition in elderly individuals.

Unraveling the Contribution of MulSOS2 in Conferring Salinity Tolerance in Mulberry (Morus atropurpurea Roxb).

Salinity is one of the most serious threats to sustainable agriculture. The Salt Overly Sensitive (SOS) signaling pathway plays an important role in salinity tolerance in plants, and the SOS2 gene plays a critical role in this pathway. Mulberry not only has important economic value but also is an important ecological tree species; however, the roles of the SOS2 gene associated with salt stress have not been reported in mulberry. To gain insight into the response of mulberry to salt stress, SOS2 (designated MulSOS2) was cloned from mulberry (Morus atropurpurea Roxb), and sequence analysis of the amino acids of MulSOS2 showed that it shares some conserved domains with its homologs from other plant species. Our data showed that the MulSOS2 gene was expressed at different levels in different tissues of mulberry, and its expression was induced substantially not only by NaCl but also by ABA. In addition, MulSOS2 was exogenously expressed in Arabidopsis, and the results showed that under salt stress, transgenic MulSOS2 plants accumulated more proline and less malondialdehyde than the wild-type plants and exhibited increased tolerance to salt stress. Moreover, the MulSOS2 gene was transiently overexpressed in mulberry leaves and stably overexpressed in the hairy roots, and similar results were obtained for resistance to salt stress in transgenic mulberry plants. Taken together, the results of this study are helpful to further explore the function of the MulSOS2 gene, which provides a valuable gene for the genetic breeding of salt tolerance in mulberry.

TMEM9 promotes lung adenocarcinoma progression via activating the MEK/ERK/STAT3 pathway to induce VEGF expression.

Abnormal Transmembrane protein 9 (TMEM9) expression has been identified in various human tumors. However, the prognostic potential and mechanistic role of TMEM9 in lung adenocarcinoma (LUAD) remain unclear. Here, we first found a significant upregulation of TMEM9 in LUAD tissues, and TMEM9 expression was positively correlated with microvessel density (MVD), T stage, and clinical stage. Survival analysis demonstrated TMEM9 was an independent indicator of poor prognosis in LUAD patients. In addition, downregulation of TMEM9 suppressed tumor growth and metastasis in vitro and in vivo models, and reduced HUVEC proliferation, migration, and tube formation in a cancer cell/HUVEC coculture model. Furthermore, TMEM9 upregulated VEGF expression, and VEGF-neutralizing antibodies reversed HUVEC angiogenesis and cancer cell migration ability caused by overexpression of TMEM9. In contrast, recombinant VEGF (rVEGF) abolished the inhibitory effect of TMEM9-knockdown LUAD cells on HUVEC angiogenesis and tumor cell migration. Moreover, we showed that TMEM9 upregulated VEGF expression by activating the mitogen-activated protein kinase/extracellular signal-regulated kinase/STAT3 (MEK/ERK/STAT3) pathway. Together, our study provides mechanistic insights into the role of TMEM9 in LUAD and highlights the potential of targeting the TMEM9/MEK/ERK/STAT3/VEGF pathway as a novel therapy for preventing LUAD progression.

Fertility preservation in males with cancer of trends, region development, and efficacy in mainland China from 16 regions Chinese sperm banks.

PURPOSE: Male cancer survivors experience confusion about fertility following cancer treatment. The aims of this study were to evaluate survivors' semen quality in different tumor type groups in China and to analyze the current situation and challenges of male cancer patients with sperm cryopreservation. METHODS: This was a multicenter retrospective study of male patients with cancer who underwent sperm cryopreservation in 16 regions of the national sperm banks over an 11-year period from 2010 to 2020. RESULTS: The number of male cancer patients with sperm cryopreservation showed an overall upward trend. The development of male cancer fertility preservation (FP) in the eastern, central, and western regions of Chinese displayed imbalance. There are seven tumor types for sperm preservation in the top incidence ten tumor types, including lymphoma, leukemia, nasopharyngeal carcinoma, sarcoma, thyroid cancer, and brain tumor. Moreover, nasopharyngeal carcinoma is a high incidence rate in China, which is related to high sperm preservation rate, different from other countries. The most percentage of males receiving sperm cryopreservation in the testicular cancers (15-39 years old) of China in 2020 was 5.55%, 1.29% in the lymphoma, and 0.39% in the leukemia. According to the type of cancer, a statistically significant lower pre-sperm density, total sperm output, and post-sperm density was observed in testicular cancers. It is worth noting that the prevalence of azoospermia 22.2% in leukemia patients attribute to urgent treatment before sperm cryopreservation. Disposition of cryopreserved sperm categories included continued storage (47.2%), discarded (9%), death (0.9%), and use (3.7%). CONCLUSION: This study provides the first comprehensive national statistical census and review of fertility preservation in male cancer patients with respect to trends, prevalence, and cancer types. The development of male cancer fertility preservation in China is imbalanced and percentage of males receiving sperm cryopreservation in the adolescent and young adult cancers was low. Sixteen human sperm banks from China analyze current problems and challenges, and then prioritize steps toward the achievement of the FP strategy framework for Healthy China 2030.

N6022 attenuates cerebral ischemia/reperfusion injury-induced microglia ferroptosis by promoting Nrf2 nuclear translocation and inhibiting the GSNOR/GSTP1 axis.

Stroke poses a significant risk of mortality, particularly among the elderly population. The pathophysiological process of ischemic stroke is complex, and it is crucial to elucidate its molecular mechanisms and explore potential protective drugs. Ferroptosis, a newly recognized form of programmed cell death distinct from necrosis, apoptosis, and autophagy, is closely associated with the pathophysiology of ischemic stroke. N6022, a selective inhibitor of S-nitrosoglutathione reductase (GSNOR), is a "first-in-class" drug for asthma with potential therapeutic applications. However, it remains unclear whether N6022 exerts protective effects in ischemic stroke, and the precise mechanisms of its action are unknown. This study aimed to investigate whether N6022 mitigates cerebral ischemia/reperfusion (I/R) injury by reducing ferroptosis and to elucidate the underlying mechanisms. Accordingly, we established an oxygen-glucose deprivation/reperfusion (OGD/R) cell model and a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to mimic cerebral I/R injury. Our data, both in vitro and in vivo, demonstrated that N6022 effectively protected against I/R-induced brain damage and neurological deficits in mice, as well as OGD/R-induced BV2 cell damage. Mechanistically, N6022 promoted Nrf2 nuclear translocation, enhancing intracellular antioxidant capacity of SLC7A11-GPX4 system. Furthermore, N6022 interfered with the interaction of GSNOR with GSTP1, thereby boosting the antioxidant capacity of GSTP1 and attenuating ferroptosis. These findings provide novel insights, showing that N6022 attenuates microglial ferroptosis induced by cerebral I/R injury through the promotion of Nrf2 nuclear translocation and inhibition of the GSNOR/GSTP1 axis.

Peri-articular elbow fracture fixations with magnesium implants and a review of current literature: A case series.

BACKGROUND: In recent years, the use of Magnesium alloy implants have gained renewed popularity, especially after the first commercially available Conformité Européenne approved Magnesium implant became available (MAGNEZIX® CS, Syntellix) in 2013. AIM: To document our clinical and radiographical outcomes using magnesium implants in treating peri-articular elbow fractures. METHODS: Our paper was based on a retrospective case series design. Intra-operatively, a standardized surgical technique was utilized for insertion of the magnesium implants. Post - operatively, clinic visits were standardized and physical exam findings, functional scores, and radiographs were obtained at each visit. All complications were recorded. RESULTS: Five patients with 6 fractures were recruited (2 coronoid, 3 radial head and 1 capitellum). The mean patient age and length of follow up was 54.6 years and 11 months respectively. All fractures healed, and none exhibited loss of reduction or complications requiring revision surgery. No patient developed synovitis of the elbow joint or suffered electrolytic reactions when titanium implants were used concurrently. CONCLUSION: Although there is still a paucity of literature available on the subject and further studies are required, magnesium implants appear to be a feasible tool for fixation of peri-articular elbow fractures with promising results in our series.

Protective effect of higher free thyroxine levels within the reference range on biliary tract cancer risk: a multivariable mendelian randomization and mediation analysis.

Background: Hepatobiliary cancer (HBC), including hepatocellular carcinoma (HCC) and biliary tract cancer (BTC), is currently one of the malignant tumors that mainly cause human death. Many HBCs are diagnosed in the late stage, which increases the disease burden, indicating that effective prevention strategies and identification of risk factors are urgent. Many studies have reported the role of thyroid hormones on HBC. Our research aims to assess the causal effects and investigate the mediation effects between thyroid function and HBC. Methods: Utilizing the Mendelian randomization (MR) approach, the study employs single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) to explore causal links between thyroid function [free thyroxine (FT4), thyroid stimulating hormone (TSH), hyperthyroidism and hypothyroidism] and HBC. Data were sourced from the ThyroidOmic consortium and FinnGen consortium. The analysis included univariable and multivariable MR analysis, followed by mediation analysis. Results: The study found a significant causal association between high FT4 levels and the reduced risk of BTC, but not HCC. However, TSH, hyperthyroidism and hypothyroidism had no causal associations with the risk of HBC. Notably, we also demonstrated that only higher FT4 levels with the reference range (FT4-RR) could reduce the risk of BTC because this protective effect no longer existed under the conditions of hyperthyroidism or hypothyroidism. Finally, we found that the protective effect of FT4-RR on BTC was mediated partially by decreasing the risk of metabolic syndrome (MetS) and reducing the waist circumference (WC). Conclusion: The findings suggest that higher FT4-RR may have a protective effect against BTC, which is partially mediated by decreased risk of MetS and a reduction in WC. This study highlights the potential role of FT4 in the pathogenesis of BTC and underscores that MetS and WC may play mediation effects as two mediators in this process.