The role and future prospects of artificial intelligence algorithms in peptide drug development.

Peptide medications have been more well-known in recent years due to their many benefits, including low side effects, high biological activity, specificity, effectiveness, and so on. Over 100 peptide medications have been introduced to the market to treat a variety of illnesses. Most of these peptide medications are developed on the basis of endogenous peptides or natural peptides, which frequently required expensive, time-consuming, and extensive tests to confirm. As artificial intelligence advances quickly, it is now possible to build machine learning or deep learning models that screen a large number of candidate sequences for therapeutic peptides. Therapeutic peptides, such as those with antibacterial or anticancer properties, have been developed by the application of artificial intelligence algorithms.The process of finding and developing peptide drugs is outlined in this review, along with a few related cases that were helped by AI and conventional methods. These resources will open up new avenues for peptide drug development and discovery, helping to meet the pressing needs of clinical patients for disease treatment. Although peptide drugs are a new class of biopharmaceuticals that distinguish them from chemical and small molecule drugs, their clinical purpose and value cannot be ignored. However, the traditional peptide drug research and development has a long development cycle and high investment, and the creation of peptide medications will be substantially hastened by the AI-assisted (AI+) mode, offering a new boost for combating diseases.

Extension of Japan's Prefectural Emission Accounting and Enrichment of Socioeconomic Data from 1990 to 2020.

With the continuous increase in carbon dioxide emissions due to human activities and the resulting severe climate issues, there is global concern about energy conservation and emission reduction. However, detailed data on energy consumption and emissions at a fine-grained scale, particularly regarding spatial dimensions and sector-specific emissions, remains insufficient and in need of refinement and timely updates. In Japan, following the Fukushima nuclear disaster, there has been a significant shift from nuclear power generation to reliance on fossil fuels across various sectors, highlighting disparities in emissions data across different regions and industries. Our work extends the emissions time series for Japan's 47 prefectures, incorporating their socioeconomic characteristics over a broader time frame and with a more detailed sectoral classification. The emissions inventory, covering the period from 1990 to 2020, is based on the consumption of the three main fossil fuels across 32 sectors, with emissions carefully allocated for regional power generation. This dataset, presented in a unified format, is expanded to include longer time scales and more detailed socioeconomic data. It is anticipated to offer crucial insights for establishing regional emission reduction targets and identifying sectoral priorities for decarbonization.

Identification of particle distribution pattern in vertical profile via unmanned aerial vehicles observation.

Below the boundary layer, the air pollutants have been confirmed to present the decreasing trend with the height in most situaitons. However, the disperiosn rate of air pollutants in the vertical profile is rarely investigated in detail, especially through in-situ measurement. With this consideration, we employed an unmanned aerial vehicle equipped with portable monitoring equipments to scrutinize the vertical distribution of PM2.5. Based on the original data, we found that PM2.5 concentration decreases gradually with altitude below the boundary layer and demonstrated an obvious linear correlation. Therefore, the vertical distribution of PM2.5 was quantified by representing the distribution of PM2.5 with the slope of PM2.5 vertical distribution. We used backward trajectories to reveal the causes of outliers (PM2.5 increasing with altitude), and found that PM2.5 in the high altitude came from the southwest. Besides, the relationship between the vertical distribution of PM2.5 and various meteorological factors was investigated using stepwise regression analysis. The results show that the four meteorological factors most strongly correlated with the slope values are: (a) the difference in relative humidity between the ground and the air; (b) the difference in temperature between the ground and the air; (c) the height of the boundary layer; and (d) the wind speed. The slope values increase with increasing the difference in relative humidity between ground and air and the difference in temperature between the ground and the air, and decrease with increasing boundary layer height and wind speed. According to the Random Forest calculations, the ground-to-air relative humidity difference is the most important at 0.718; the wind speed is the least important at 0.053; and the ground-to-air temperature difference and boundary layer height are 0.140 and 0.088, respectively.

Should non-invasive prenatal testing be recommended for patients who achieve pregnancy with PGT?

OBJECTIVE: To determine whether non-invasive prenatal testing is an alternative testing option to preimplantation genetic testing (PGT) in pregnant patients. METHODS: This was a retrospective study of the clinical outcomes of patients who underwent PGT and invasive or non-invasive pregnancy testing after euploid blastocyst transfer at our IVF centre between January 2017 and December 2022. RESULTS: In total, 321 patients were enrolled in this study, 138 (43.0%) received invasive pregnancy testing, and 183 (57.0%) patients underwent non-invasive testing. The mean age of the patients in Group 2 was higher than that of the patients in Group 1 (35.64 ± 4.74 vs. 31.04 ± 4.15 years, P < 0.001). The basal LH and AMH levels were higher in Group 1 than in Group 2 (4.30 ± 2.68 vs. 3.40 ± 1.88, P = 0.003; 5.55 ± 11.22 vs. 4.09 ± 3.55, P = 0.012), but the clinical outcomes were not significantly different. Furthermore, the clinical outcomes of patients undergoing invasive testing were similar to those of patients undergoing non-invasive testing with the same PGT indication. CONCLUSION: Our results suggest that non-invasive pregnancy testing is a suitable alternative option for detecting the foetal chromosomal status in a PGT cycle. However, the usefulness of non-invasive testing in PGT-M patients is still limited.

ADSC-Exos enhance functional recovery after spinal cord injury by inhibiting ferroptosis and promoting the survival and function of endothelial cells through the NRF2/SLC7A11/GPX4 pathway.

BACKGROUND: Spinal cord injury (SCI) is a devastating disease that causes major motor, sensory and autonomic dysfunctions. Currently, there is a lack of effective treatment. In this study, we aimed to investigate the potential mechanisms of Exosomes from adipose-derived stem cells (ADSC-Exos) in reducing ferroptosis and promoting angiogenesis after spinal cord injury. METHODS: We isolated ADSC-Exos, the characteristics of which were confirmed. In vitro, we tested the potential of ADSC-Exos to promote the survival and function of human brain microvascular endothelial cells (HBMECs) and analyzed the ferroptosis of HBMECs. In vivo, we established rat models of SCI and locally injected ADSC-Exos to verify their efficacy. RESULTS: ADSC-Exos can reduce reactive oxygen species (ROS) accumulation and cell damage induced by an excessive inflammatory response in HBMECs. ADSC-Exos inhibit ferroptosis induced by excessive inflammation and upregulate the expression of glutathione peroxidase 4(GPX4) in HBMECs. It can also effectively promote proliferation, migration, and vessel-like structure formation. In vitro, ADSC-Exos improved behavioral function after SCI and increased the number and density of blood vessels around the damaged spinal cord. Moreover, we found that ADSC-Exos could increase nuclear factor erythroid-2-related factor 2(NRF2) expression and nuclear translocation, thereby affecting the expression of solute carrier family 7 member 11(SLC7A11) and GPX4, and the NRF2 inhibitor ML385 could reverse the above changes. CONCLUSION: Our results suggest that ADSC-Exos may inhibit ferroptosis and promote the recovery of vascular and neural functions after SCI through the NRF2/SLC7A11/GPX4 pathway. This may be a potential therapeutic mechanism for spinal cord injury.

Association between dietary diversity, sedentary time outside of work and depressive symptoms among knowledge workers: a multi-center cross-sectional study.

BACKGROUND: Low-diversity diets and sedentary status are risk factors for depressive symptoms, while knowledge workers were ignored before. The purpose of this current study was to examine the relationship between dietary diversity, sedentary time spent outside of work, and depressive symptoms among knowledge workers. STUDY DESIGN AND METHODS: This was a multicenter and cross-sectional design that included 118,723 knowledge workers. Participants self-reported online between January 2018 and December 2020. Demographic information, the Dietary Diversity Scale, the Patient Health Questionnaire-9, dietary habits (which included eating three meals on time, midnight snacking, overeating, social engagement, coffee consumption, sugary drink consumption, smoking and alcohol use), sedentary time spent outside of work and physical activity were investigated. RESULTS: The relationships between demographic information, dietary habits and dietary diversity, and depressive symptoms were estimated. Compared with the first and second levels of dietary diversity, the third level of dietary diversity (OR: 0.91; 95% CI: 0.84-0.98) reduced the risk of depressive symptoms. Knowledge workers with different degrees of sedentary status (2-4 h (OR: 1.11; 95% CI: 1.07-1.14), 4-6 h (OR: 1.21; 95% CI: 1.17-1.26), and > 6 h (OR: 1.49; 95% CI: 1.43-1.56), presented a progressively higher risk of depressive symptoms. CONCLUSION: High amounts of sedentary time spent after work and low levels of dietary diversity are risk factors for depressive symptoms. In addition, an irregular diet and overeating are also major risk factors for knowledge workers.

Transforaminal endoscopic lumbar discectomy using a 45° puncture angle and foraminotomy versus traditional THESYS for L5/S1 lumbar disc herniation: a prospective randomized controlled trial.

PURPOSE: Prospective comparison of the efficacy and safety of transforaminal endoscopic lumbar discectomy (TELD) with a 45° puncture angle versus traditional Thomas Hoogland endoscopy spine systems (THESYS) for the surgical treatment of L5/S1 lumbar disc herniation (LDH). METHODS: Consecutive patients with L5/S1 LDH who underwent TELD were randomized (1:1) assigned to the 45° TELD group and the THESYS group. Clinical outcomes were assessed at pre-operation, 1-day and 3/6-months post-operation till final follow-up. Surgical-related parameters, visual analogue scale (VAS) score, oswestry disability index (ODI), and modified MacNab criteria, and surgical complications were recorded and analysed. RESULTS: All patients were followed up for at least 24 months. Compared to the THESYS group, the 45° TELD group had a shorter operative time (P < 0.001) and intraoperative radiation time (P < 0.001) and a smaller VAS score for back pain (P < 0.001) and leg pain intraoperatively (P < 0.001). The VAS and ODI in the 45° TELD group were significantly better than those in the THESYS group within 3 months postoperatively. However, from 3 months on, both groups showed comparable VAS and ODI. There was no significant difference between the two groups of modified MacNab criteria. There were two cases of residual disc and two cases of recurrence that required reoperation in the THESYS group. CONCLUSION: For L5/S1 LDH, the 45° TELD technique was superior to traditional THESYS in terms of surgery-related parameters and faster improvement of VAS and ODI, with a lower complication rate.

Carbon footprint and embodied nutrition evaluation of 388 recipes.

Food consumption, which delivers fundamental energy and essential nutrients to human beings, is crucial for achieving a series of sustainable goals. Alongside rising population growth and living standards, there has been a significant increase in food cultivation demands, supply chain complexities, and waste management. Therefore, to protect human health and the environment, promoting sustainable food systems and the uptake of sustainable dietary habits are vital. Yet, information on the environmental and health impact of dietary choices remains inconsistent across multiple evaluation methods, which fail to deliver essential ideas to consumers. In this study, we formulate an integrated approach using Environmentally Extended Input-Output analysis, covering the food supply chain from production to the distribution phase, complemented with a hybrid Life Cycle Assessment for cooking and disposal processes, to quantify the carbon footprint of specific recipes. Our dataset also includes the distinct nutritional values of each recipe. This dataset not only informs the food industry and recipe platforms, enabling more sustainable choices, but also helps individuals balance nutritional value with environmental impact, leading to more informed and sustainable dietary decisions.

From basic to clinical: Anatomy of Denonvilliers' fascia and its application in laparoscopic radical resection of rectal cancer.

The total mesorectal excision (TME) approach has been established as the gold standard for the surgical treatment of middle and lower rectal cancer. This approach is widely accepted to minimize the risk of local recurrence and increase the long-term survival rate of patients undergoing surgery. However, standardized TME causes urogenital dysfunction in more than half of patients, thus lowering the quality of life of patients. Of note, pelvic autonomic nerve damage during TME is the most pivotal cause of postoperative urogenital dysfunction. The anatomy of the Denonvilliers' fascia (DVF) and its application in surgery have been investigated both nationally and internationally. Nevertheless, controversy exists regarding the basic to clinical anatomy of DVF and its application in surgery. Currently, it is a hotspot of concern and research to improve the postoperative quality of life of patients with rectal cancer through the protection of their urinary and reproductive functions after radical resection. Herein, this study systematically describes the anatomy of DVF and its application in surgery, thus providing a reference for the selection of surgical treatment modalities and the enhancement of postoperative quality of life in patients with middle and low rectal cancer.

Research landscape and frontiers of non-alcoholic steatohepatitis-associated hepatocellular carcinoma: a bibliometric and visual analysis.

Background: Due to the widespread prevalence of caloric excess and sedentary behavior on a global scale, there is a growing body of epidemiological evidence indicating that non-alcoholic steatohepatitis (NASH) has rapidly become a leading aetiology underlying of hepatocellular carcinoma (HCC). In light of the escalating incidence of NASH-associated HCC (NASH-HCC), it is imperative to mitigate the impending burden. While there has been an increase in global awareness regarding this issue, it has yet to be examined from a bibliometric standpoint. Therefore, this study seeks to provide a comprehensive bibliometric analysis to characterize the evolution of this field. Method: The present study utilized the Web of Science Core Collection (WoSCC) to identify publications pertaining to NASH-HCC over the past 2 decades. Employing Vosviewer 1.6.19, CiteSpace 6.2.R2, and the Analysis Platform of Bibliometrics, the study conducted an analysis of various dimensions including the quantity of publications, countries, institutions, journals, authors, co-references, keywords, and trend topics in this field. Results: A comprehensive analysis of 3,679 publications pertaining to NASH-HCC, published between 1 January 2002 and 1 April 2023, was conducted. The field in question experienced a rapid increase in publications, with the United States serving as the central hub. Collaboration between institutions was more extensive than that between countries. Notably, HEPATOLOGY (n = 30,168) emerged as the most impactful journal, and Zobair M. Younossi (n = 10,025) as the most frequently cited author in co-citations. The most commonly cited references were KLEINER DE, 2005, HEPATOLOGY (n = 630), followed by YOUNOSSI ZM, 2016, HEPATOLOGY (n = 493). The author keywords were categorized into three distinct clusters, namely, Cluster 1 (Mechanism), Cluster 2 (Factors), and Cluster 3 (Diagnosis). Analysis of high-frequency co-occurring keywords and topical trends revealed emphasis on molecular mechanisms in current research. "macrophages" and "tumor microenvironment" were active research hotspots at present in this field. Conclusion: A bibliometric analysis was performed for the first time on publications pertaining to non-alcoholic steatohepatitis-hepatocellular carcinoma, uncovering co-research networks, developmental trends, and current research hotspots. The emerging frontiers of this field focused on the macrophages and tumor microenvironment, especially the tumor-associated macrophages, offering a fresh perspective for future research directions.

Cry1Δ11 mutation induces ADHD-like symptoms through hyperactive dopamine D1 receptor signaling.

Attention-deficit hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder that affects approximately 5.3% of children and approximately 2.5% of adults. There is an intimate relationship between ADHD and sleep disturbance. Specifically, individuals carry a mutation in the core circadian gene CRY1 (c. 1657 + 3A > C), which results in the deletion of exon 11 expression in the CRY1 protein (CRY1Δ11), causing them to exhibit typical ADHD symptoms. However, the underlying mechanism is still elusive. In this study, we demonstrate that Cry1Δ11 (c. 1717 + 3A > C) mice showed ADHD-like symptoms, including hyperactivity, impulsivity, and deficits in learning and memory. A hyperactive cAMP signaling pathway was found in the nucleus accumbens (NAc) of Cry1Δ11 mice. We further demonstrated that upregulated c-Fos was mainly localized in dopamine D1 receptor-expressing medium spiny neurons (DRD1-MSNs) in the NAc. Neuronal excitability of DRD1-MSNs in the NAc of Cry1Δ11 mice was significantly higher than that of WT controls. Mechanistically, the CRY1Δ11 protein, in contrast to the WT CRY1 protein, failed to interact with the Gαs protein and inhibit DRD1 signaling. Finally, the DRD1 antagonist SCH23390 normalized most ADHD-like symptoms in Cry1Δ11 mice. Thus, our results reveal hyperactive DRD1 signaling as an underlying mechanism and therapeutic target for ADHD induced by the highly prevalent CRY1Δ11 mutation.

Extension and update of multiscale monthly household carbon footprint in Japan from 2011 to 2022.

Household consumption significantly contributes to greenhouse gas emissions as it is the largest component of final demand in the national accounting system. Nevertheless, there is an apparent lack of comprehensive and consistent datasets detailing emissions from household consumption. Here, we expand and update Japan's multiscale monthly household carbon footprint from January 2011 to September 2022, combining data from government statistics and surveys. We constructed a dataset comprising 37,692 direct and 4,852,845 indirect emission records, covering households at the national, regional, and prefectural city levels. The dataset provides critical spatiotemporal information that allows for revealing carbon emission patterns, pinpointing primary sources of emissions, and discerning regional variances. Moreover, the inclusion of micro-scale carbon footprint data enables the identification of specific consumption habits, thereby regulating individual consumption behavior to achieve a low-carbon society.

Circ_0000419 acts as a tumor suppressor in gastric cancer development via regulating miR-300/RGMB axis.

OBJECTIVE: Dysregulated circular RNAs (circRNAs) have been verified to function in the development of gastric cancer (GC). The current study was designed to investigate the role of circ_0000419 in GC progression, and the potential mechanistic pathway. METHODS: Relative expression of circ_0000419, microRNA-300 (miR-300) and Repulsive Guidance Molecule B (RGMB) was analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay. Cell metastasis, including migration and invasion, was assessed by wound healing and Transwell assays. Glucose consumption and lactate production were examined using kits. The association between miR-300 and circ_0000419 or RGMB was validated by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assays. Role of circ_0000419 in vivo was determined by xenograft experiment. RESULTS: Circ_0000419 and RGMB were downregulated, while miR-300 was upregulated in GC tissues and cells. Gain of circ_0000419 inhibited migration, invasion and glycolysis in GC cells, which was attenuated by introduction of miR-300 or silencing of RGMB. Circ_0000419 sponged miR-300, and RGMB was direct target of miR-300. Circ_0000419 overexpression could block GC tumor growth in vivo. CONCLUSION: Circ_0000419 inhibited GC cell migration, invasion and glycolysis through regulation of miR-300/RGMB axis, at least in part, affording a molecular target for GC treatment.

Impact of urinary sodium excretion on the prevalence and incidence of metabolic syndrome: a population-based study.

OBJECTIVE: To evaluate the association of metabolic syndrome (MetS) risk with 24-hour urinary sodium excretion (24hUNaE) estimated from spot urine samples. DESIGN: Serial cross-sectional studies were conducted, and those with multiple repeated examinations were used to assess the MetS incidence risk. SETTING AND PARTICIPANTS: A health check-up programme was conducted between 2018 and 2021 and enrolled 59 292 participants to evaluate the relationship between MetS risk and 24hUNaE in the Third Xiangya Hospital, Changsha, China. Among these participants, 9550 had at least two physical examinations during this period, which were used to evaluate the association of a new occurrence of MetS with 24hUNaE. OUTCOMES: Guidelines for the prevention and treatment of dyslipidaemia in Chinese adults (revised in 2016) were used to define prevalent and incident MetS. RESULTS: The prevalence of MetS was 19.3% at the first check-up; among individuals aged ≤55 years, the risk was higher in men than women, while among older individuals, a similar prevalence was observed in both sexes. A significant increase in MetS prevalence was observed per unit increase in 24hUNaE (adjusted OR (AOR) 1.11; 95% CI 1.09 to 1.13), especially for the prevalence of central obesity and elevated blood pressure. Additionally, 27.4% of the participants among the 7842 participants without MetS at the first check-up (male vs female: 37.3% vs 12.9%) were found to have a new occurrence of MetS at the second, third and/or fourth check-ups. A 25% increase in MetS incidence was observed per unit increase in 24hUNaE (95% CI 1.19 to 1.32), which was more prominent in the participants with a new occurrence of central obesity and elevated fasting blood glucose. CONCLUSIONS: Although the prevalence of MetS seemed stable, new occurrences of MetS remained high, which might result in MetS recurrence. The influence of sodium intake on MetS development is probably attributed to the increase in blood pressure and central obesity, but a new occurrence of MetS may develop through elevated blood glucose and central obesity.

Gastrodiabawanglingensis (Orchidaceae, Epidendroideae), a new species from Hainan Island, China.

Gastrodiabawanglingensis, a new species of Orchidaceae from Hainan Island, China, is described and illustrated. It is morphologically similar to G.theana, G.albidoides and G.albida with dwarf habits, scarcely opening flowers, elongated fruit stems, curved and fleshy perianth tubes and similar columns and lips, but can be easily distinguished from them by having a pair of lateral wings bent outwards at the apex of the column and lateral wings with acuminate tips lower than the anther. According to the IUCN Red List Categories and Criteria, the new species is assessed as Endangered (EN). The plastome of G.bawanglingensis is greatly reduced and reconfigured with approximately 30876 bp in size and 25.36% in GC content. Morphological characteristics and molecular phylogenetic results based on chloroplast gene sequences support the recognition of G.bawanglingensis as a new species within Gastrodia.

Association of long-term ambient fine particulate matter (PM2.5) and incident non-alcoholic fatty liver disease in Chinese adults.

Air pollution is increasingly recognized as an important environmental risk factor for non-alcoholic fatty liver disease (NAFLD). However, epidemiologic evidence on long-term exposure to high air pollution concentrations with incident NAFLD is still very limited. Here, we constructed a population-based dynamic cohort involving 17,106 subjects who were enrolled between 2005 and 2013 and subsequently followed until 2017, combined with a high-resolution ambient fine particulate matter ≤2.5 µm (PM2.5) dataset, to investigate the association of long-term PM2.5 exposure (cumulative annual average levels ranged from 36.67 to 111.16 µg/m3) with NAFLD incidence (N = 4,640). We estimated the adjusted hazard ratio (HR) for incident NAFLD among those exposed to the highest quartile of PM2.5 was 2.04 [95% confidence interval (CI), 1.80-2.30] compared with individuals exposed to the lowest quartile of PM2.5. The dose-response relationships for PM2.5 are non-linear for NAFLD across the exposure distribution. Further stratified analyses revealed that lean (<23 kg/m2), younger (<40-year-old), and women individuals appeared more vulnerable to the harmful effects of PM2.5 exposure. Our study suggests a greater long-term high ambient PM2.5 exposure is associated with an increased risk of NAFLD in Chinese adults, particularly in specific groups, including lean, women, and younger people.

Has_circ_0071803 promotes colorectal cancer progression by regulating miR-330-5p/MAPK signaling pathway.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. A lack of effective targeted therapies against CRC makes the treatment challenging. Here, we report a circular RNA (circRNA), has_circ_0071803, functioning as an oncogene in CRC. Circ_0071803 was upregulated in CRC tissues and cell lines, and its expression levels were inversely correlated with the prognosis and survival rate of patients with CRC. Circ_0071803 knockdown suppressed cell proliferation, migration, and invasion in CRC. Moreover, we found that circ_0071803 sponged miR-330-5p, thereby upregulating mitogen-activated protein kinase 1 (MAPK1) in CRC cells. The suppression of cell activities by circ_0071803 knockdown were rescued by miR-330-5p inhibition or MAPK1 overexpression. Collectively, our findings elucidate that circ_0071803 promotes CRC progression by regulating the miR-330-5p/MAPK1 pathway, providing potential therapeutic targets for designing effective targeted treatments.