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Pescadillo ribosomal biogenesis factor 1 (PES1), a nucleolar protein initially identified in zebrafish, plays an important role in embryonic development and ribosomal biogenesis. Notably, PES1 has been found to be overexpressed in a number of cancer types, where it contributes to tumorigenesis and cancer progression by promoting cell proliferation, suppressing cellular senescence, modulating the tumor microenvironment (TME) and promoting drug resistance in cancer cells. Moreover, recent emerging evidence suggests that PES1 expression is significantly elevated in the livers of Type 2 diabetes mellitus (T2DM) and obese patients, indicating its involvement in the pathogenesis of metabolic diseases through lipid metabolism regulation. In this review, we present the structural characteristics and biological functions of PES1, as well as complexes in which PES1 participates. Furthermore, we comprehensively summarize the multifaceted role of PES1 in various diseases and the latest insights into its underlying molecular mechanisms. Finally, we discuss the potential clinical translational perspectives of targeting PES1, highlighting its promising as a therapeutic intervention and treatment target.

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OBJECTIVE: Excessive weight gain, obesity, or insufficient weight gain during pregnancy can adversely affect both the mother and her offspring. This study aims to investigate the relationship between pregnant women's self-perception and beliefs and their body weight management during pregnancy. METHODS: A cross-sectional survey involving 350 pregnant women in Changsha City was conducted from July to September 2023. Instruments included a sociodemographic data sheet, protective motivation questionnaire for pregnancy body quality management, and scales measuring body image, anxiety, self-efficacy, and social support. Univariate analysis and multiple linear regression were employed to identify factors influencing protective motivation for body quality management during pregnancy. RESULTS: The average score of the protective motivation questionnaire was 124 (SD = 13.07), suggesting a need for enhanced weight management. Key factors influencing protective motivation included household income, cooperation with healthcare workers, sources of pregnancy information, midnight snacking habits, prepregnancy exercise, body image, and self-efficacy (P < 0.05). CONCLUSION: The study highlights significant factors influencing pregnant women's motivation for body quality management. These include economic status, healthcare collaboration, information accessibility, lifestyle habits, and psychological factors. The findings underscore the need for healthcare professionals to integrate these factors into pregnancy care programs to improve body quality management.

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BACKGROUD: Left bundle branch pacing (LBBP) is a novel physiological pacing modality. However, whether it delivers comparable efficacy with different capture sites in heart failure (HF) patients remains unclear. OBJECTIVE: This study aims to assess the association between different pacing sites and the response of LBBP . METHODS: Forty-three consecutive HF patients , referred for successful LBBP implantation, were prospectively recruited in this study. Patients were assigned to 3 subgroups according to the paced QRS complex morphology (left bundle branch trunk pacing (LBTP), left posterior fascicular pacing (LPFP) or left anterior fascicular pacing (LAFP) groups). Echocardiograms, electrocardiograms were recorded and analyzed at baseline and 6-month follow-up. RESULTS: The response rate was 95.0%, 88.2%, 83.3% in LBTP, LPFP and LAFP groups, respectively. All subgroups were efficient in narrowing QRS complex(ΔQRS: 62.4±10.4 ms, 54.7±14.2ms, 58.2±14.5ms) and improving cardiac function (ΔLVEF: 25.7±8.1%, 15.3±8.1%, 18.8±4.4%). Compared with left fascicle pacing(LFP), LBTP resulted in longer LVAT (76.5±10.2ms vs 82.3±6.5ms; P=0.037) , shorter QRSid (128.0±6.0ms vs 113.3±5.2ms; P＜0.0001),along with better improvement in septal systolic longitudinal strain(P=0.007) and lateral-septal myocardial loading inhomogeneity (P=0.036). Linear regression analysis further revealed LBB capture sites was strongly associated with the improvement of peak strain dispersion (PSD) (model R2 = 0.586, P =0.042) and LVEF (model R2 = 0.425, P <0.0001). CONCLUSIONS: Different LBB capture sites led to subtle difference in mechanical synchrony , which may in-turn affect LVEF improvement in HF patients.

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This review examines the role of model-informed drug development (MIDD) in advancing antibacterial and antiviral drug development, with an emphasis on the inclusion of host system dynamics into modeling efforts. Amidst the growing challenges of multidrug resistance and diminishing market returns, innovative methodologies are crucial for continuous drug discovery and development. The MIDD approach, with its robust capacity to integrate diverse data types, offers a promising solution. In particular, the utilization of appropriate modeling and simulation techniques for better characterization and early assessment of drug resistance are discussed. The evolution of MIDD practices across different infectious disease fields is also summarized, and compared to advancements achieved in oncology. Moving forward, the application of MIDD should expand into host system dynamics as these considerations are critical for the development of "live drugs" (e.g. chimeric antigen receptor T cells or bacteriophages) to address issues like antibiotic resistance or latent viral infections.

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Osteoarthritis (OA) is a highly incident total joint degenerative disease with cartilage degeneration as the primary pathogenesis. The cartilage matrix is mainly composed of collagen, a matrix protein with a hallmark triple-helix structure, which unfolds with collagen degradation on the cartilage surface. A collagen hybridizing peptide (CHP) is a synthetic peptide that binds the denatured collagen triple helix, conferring a potential disease-targeting possibility for early-stage OA. Here, we constructed an albumin nanoparticle (An) conjugated with CHP, loaded with a chondrogenesis-promoting small molecule drug, kartogenin (KGN). The CHP-KGN-An particle exhibited sustained release of KGN in vitro and prolonged in vivo retention selectively within the degenerated cartilage in the knee joints of model mice with early-stage OA. Compared to treatment with KGN alone, CHP-KGN-An robustly attenuated cartilage degradation, synovitis, osteophyte formation, and subchondral bone sclerosis in OA model mice and exhibited a more prominent effect on physical activity improvement and pain alleviation. Our study showcases that targeting the degenerated cartilage by collagen hybridization can remarkably promote the efficacy of small molecule drugs and may provide a novel delivery strategy for early-stage OA therapeutics.

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BACKGROUND: Long-term exposure to UVB induces DNA damage, inflammatory response, mitochondrial dysfunction, and apoptosis in skin cells, thus causing skin photodamage. Research has demonstrated the noteworthy antioxidant, anti-inflammatory, DNA repair, and mitochondrial protective properties of keratinocyte growth factor-2 (KGF-2). METHODS: To examine the impact of KGF-2 on UVB-triggered skin photodamage in mice, hair-removed mice were initially exposed under UVB radiation and subsequently treated with KGF-2 hydrogel and repeated for 6 days. On day 7, the assessment of histopathological alterations, inflammation, DNA damage, mitochondrial function, and apoptosis in mouse skin was assessed. RESULTS: It was found that KGF-2 could effectively relieve cutaneous photodamage symptoms and inhibit epidermal proliferation in mice. Meanwhile, KGF-2 was found to significantly reduce DNA damage, attenuate the inflammatory response, and inhibit the mitochondria-mediated intrinsic apoptotic pathway in the UVB-exposed mouse skin photodamage model. CONCLUSION: To summarize, our results indicated that KGF-2 reduces the severity of mouse skin photodamage caused by UVB rays by attenuating DNA damage and the inflammatory response, besides inhibiting the mitochondria-mediated intrinsic apoptosis pathway.

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Epidemiological studies have shown that coke oven emissions (COEs) affect the deterioration of asthma, but has not been proven by experimental results. In this study, we found for the first time that COEs exacerbate allergen house dust mite (HDM)-induced allergic asthma in the mouse model. The findings reveal that airway inflammation, airway remodeling and allergic reaction were aggravated in the COE + HDM combined exposure group compared with the individual exposure group. Mechanism studies indicated higher levels of iron and MDA in the COE + HDM combined exposure group, along with increased expression of Ptgs2 and reduced GPX4 expression. Iron chelator deferoxamine (DFO) effectively inhibited ferroptosis induced by COE synergistically with HDM in vitro. Further studies highlighted the role of ferritinophagy in the COE + HDM-induced ferroptosis. 3-methyladenine (3-MA) could inhibit ferroptosis in the COE + HDM exposure group. Interestingly, we injected DFO intraperitoneally into mice in the combined exposure group and found DFO could significantly inhibit the COE-exacerbated ferroptosis and allergic asthma. Our findings link ferroptosis with COE-exacerbated allergic asthma, implying that ferroptosis may have important therapeutic potential for asthma in patients with occupational exposure of COE.

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Community-Acquired Respiratory Distress Syndrome Toxin (CARDS TX) is a unique exotoxin produced by Mycoplasma pneumoniae (MP) and has been confirmed to possess ADP-ribosyltransferase (ART) and vacuolating activities. CARDS TX binds to receptors on the surfaces of mammalian cells followed by entry into the cells through clathrin-mediated endocytosis, and exerts cytotoxic effects by undergoing retrograde transport and finally cleavage on endosomes and cellular organelles. In addition, CARDS TX can trigger severe inflammatory reactions resulting in airway dysfunction, producing allergic inflammation and asthma-like conditions. As a newly discovered virulence factor of MP, CARDS TX has been extensively studied in recent years. As resistance to macrolide drugs has increased significantly in recent years and there is no vaccine against MP, the development of a vaccine targeting CARDS TX is considered a potential preventive measure. This review focuses on recent studies and insights into this toxin, providing directions for a better understanding of MP pathogenesis and treatment. IMPORTANCE: A serious hazard to worldwide public health in recent years, Mycoplasma pneumoniae (MP) is a prominent bacterium that causes community-acquired pneumonia (CAP) in hospitalized children. Due to their high prevalence and fatality rates, MP infections often cause both respiratory illnesses and extensive extrapulmonary symptoms. It has recently been shown that MP produces a distinct exotoxin known as Community-Acquired Respiratory Distress Syndrome Toxin (CARDS TX). Mycoplasma pneumoniae pneumonia (MPP)-like tissue injury is caused by this toxin because it has both ADP-ribosyltransferase and vacuolating properties. A better knowledge of MP etiology and therapy is provided by this review, which focuses on latest research and insights into this toxin.

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BACKGROUND: Cardiovascular disease originates in early life. We aimed to investigate the association between breastfeeding in infancy and cardiovascular disease in adult life. METHODS: We followed 364,240 participants from UK Biobank aged 40-73 years from 2006 - 2010 to 2021. Information on breastfeeding in infancy was self-reported by questionnaire. Cox proportional hazard regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the association between breastfeeding and cardiovascular disease in middle-aged and older adulthood. The multivariable Cox models were used by adjusting for the age (used as the time scale), sex, ethnicity, assessment centre, birth weight, multiple birth status, maternal smoking during pregnancy, Townsend deprivation index, smoking status, alcohol drinker status, physical activity, and menopausal status for women. Binary and multinomial multivariable logistic regression models were used to explore the associations of breastfeeding in infancy with cardiovascular disease risk factors including obesity, body composition, metabolic and inflammatory disorders. RESULTS: During a median of 12.6 years of follow-up, we documented 29,796 new cases of cardiovascular disease, including 24,797 coronary heart disease and 6229 stroke. The multivariable adjusted HRs for breastfed versus non-breastfed were 0.94 (95% CI: 0.91, 0.96) for cardiovascular disease, 0.94 (95% CI: 0.91, 0.96) for coronary heart disease, and 0.95 (95% CI: 0.89, 1.01) for stroke. Furthermore, the strength of observed association between breastfeeding and cardiovascular disease seems to decrease with age (P for interaction <0.001), and increase with polygenic risk for cardiovascular disease (P for interaction <0.001). Consistently, breastfeeding in infancy was associated with cardiovascular disease risk factors including lower body mass index 0.92 (95% CI: 0.89, 0.95), body fat percentage 0.85 (95% CI: 0.83, 0.87), android to gynoid fat ratio 0.89 (95% CI: 0.83, 0.96), visceral adipose tissue 0.92 (95% CI: 0.84, 1.01), as well as lower C-reactive protein level 0.95 (95% CI: 0.94, 0.97) and a lower risk of metabolic syndrome 0.89 (95% CI: 0.85, 0.92). CONCLUSIONS: Breastfeeding in infancy was associated with a lower risk of cardiovascular disease in middle-aged and older adulthood. Promoting breastfeeding is vital not only for promoting child health, but also for halting the increasing trend of cardiovascular disease in adults.

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The global incidence of non-tuberculous mycobacteria (NTM) infections is on the rise. This study systematically searched several databases, including PubMed, Web of Science, Google Scholar, and two Chinese libraries (Chinese National Knowledge Infrastructure and Wanfang) to identify relevant published between 2013 and 2023 related to the isolation of NTM in clinical specimens from various countries and provinces of China. Furthermore, a comprehensive literature review was conducted in PubMed and Google Scholar to identify randomized clinical trials, meta-analyses, systematic reviews, and observational studies that evaluated the diagnostic accuracy and impact of laboratory detection methods on clinical outcomes. This review presented the most recent epidemiological data and species distributions of NTM isolates in several countries and provinces of China. Moreover, it provided insights into laboratory bacteriological detection, including the identified strains, advantages and disadvantages, recent advancements, and the commercial Mycobacterium identification kits available for clinical use. This review aimed to aid healthcare workers in understanding this aspect, enhance the standards of clinical diagnosis and treatment, and enlighten them on the existing gaps and future research priorities.

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BACKGROUND: As a medicinal and food homologous plant, Rosa damascena is not only highly ornamental, but also rich in a variety of active ingredients such as polyphenols and flavonoids. It is widely used in cosmetics, food and pharmaceutical industries. OBJECTIVE: To study the in vitro efficacy of Rosa damascena solid state fermentation liquid (RDF) and water extract (RDE). METHODS: Firstly, the effect of RDF and RDE on the proliferation rate of B16F10 cells was detected by CCK-8 method, and the melanin content was measured by sodium hydroxide lysis method to evaluate the whitening effect of them. Finally, the antioxidant, anti-wrinkling and soothing effects of RDF and RDE were evaluated by biochemical methods in vitro. RESULTS: RDF and RDE within a certain concentration range (0.05%-0.5%) had no effect on the proliferation of B16F10 cells. Compared with Rosa damascena extract (RDE), RDF showed significant effects on bleaching, antioxidant, anti-wrinkling and soothing, among which 0.5% RDF showed the best effect. CONCLUSION: Both RDF and RDE at a certain concentration have effect on skin care in vitro, but the effect of RDF is more significant than that of RDE.

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Singerocybe alboinfundibuliformis (Seok et al.) Yang, Qin & Takah 2014 is an edible mushroom distributed in several East or Southeast Asian countries. Herein, we report the mitochondrial genome of S. alboinfundibuliformis based on Illumina sequencing data. The overall length of the mitochondrial genome is 64,279 bp, with a GC content of 29.0%. It contains 14 typical protein-coding genes, 27 tRNA genes, two rRNA genes, and 13 intergenic ORFs. Most of these genes (39 out of 56) are transcribed at the forward strand, and few (17 out of 56) are transcribed at the reverse strand. Among these genes, only the rnl gene is invaded by an intron, and all other genes are intron-free. Phylogenetic analysis based on mitochondrial amino acid sequences supports the phylogenetic position of S. alboinfundibuliformis in Clitocybaceae, being close to Lepista sordida (Schumach.) Singer 1951. This study serves as a springboard for future investigation on fungal evolution in Clitocybaceae.

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The environmental concern posed by toxic heavy metal pollution in soil and water has grown. Ca-based layered double hydroxides (LDHs) have shown exceptional efficacy in eliminating heavy metal cations through the formation of super-stable mineralization structures (SSMS). Nevertheless, it is still unclear how the intricate coordination environment of Ca2+ in Ca-based LDH materials affects the mineralization performance, which hinders the development and application of Ca-based LDH materials as efficient mineralizers. Herein, we discover that, in comparison to a standard LDH, the mineralization efficiency for Cd2+ ions may be significantly enhanced in the pentacoordinated structure of defect-containing Ca-5-LDH utilizing both density functional theory (DFT) and ab initio molecular dynamics (AIMD) simulations. Furthermore, the calcination-reconstruction technique can be utilized to successfully produce pentacoordinated Ca-5-LDH. Subsequent investigations verified that Ca-5-LDH exhibited double the mineralization performance (421.5 mg g-1) in comparison to the corresponding pristine seven coordinated Ca-7OH/H2O-LDH (191.2 mg g-1). The coordination-relative mineralization mechanism of Ca-based LDH was confirmed by both theoretical calculations and experimental results. The understanding of LDH materials and their possible use in environmental remediation are advanced by this research.

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BACKGROUND: The emergence of the Nerve Growth Factor (NGF) has promoted the development of neuroprotective therapy; however, it has little effect on cerebral ischemia because of its poor Blood-Brain Barrier (BBB) permeability. Specific Mode Electroacupuncture Stimulation (SMES) can open BBB safely and effectively; however, it has shown inconclusive clinical effects and indirect clinical evidence in the recovery phase. Hence, the authors conducted a multicentre, randomized, placebo-controlled, assessor-blinded clinical trial to assess the effectiveness and safety of SMES combined with NGF treatment used during ischaemic stroke recovery. METHODS: A total of 288 stroke patients from three hospitals will be recruited and randomly allocated to four groups: acupuncture + placebo, acupuncture + NGF, SMES + placebo, and SMES + NGF, in a 1:1:1:1 ratio. Assessment data will be collected at baseline, 2-weeks, and 4-weeks during the treatment period, as well as at the 4-week and 8-week follow-up after treatment completion. The primary outcome measure will be the basic cure rate. The secondary outcome measures include the simplified Modified Barthel Index, Timed Up and Go Test, Fugl-Meyer Assessment of Motor Function Score, Tinetti Performance Oriented Mobility Assessment, Montreal Cognitive Assessment, and Loewenstein Occupational Therapy Cognitive Assessment. Moreover, resting-state functional magnetic resonance imaging and Functional near-infrared spectroscopy can detect changes in cerebral blood flow and brain function and investigate the relationship between the clinical efficacy and mechanism of the prescribed interventions. CONCLUSION: This study will provide clinical evidence for the efficacy and safety of SMES combined with NGF in the treatment of stroke patients.

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Unraveling biodiversity patterns and their driving processes is paramount in ecology and biogeography. However, there remains a limited understanding regarding the underlying mechanisms of community assembly, particularly in alpine streams where significant elevation gradients and habitat heterogeneity exist. We investigated the patterns and drivers of beta diversity, explicitly focusing on taxonomic and functional diversity, in the three parallel rivers region in China. We employed a beta diversity partitioning approach to examine the turnover and nestedness components of beta diversity and further deconstructed the diatom community into attached and unattached groups. Our results revealed distinct diversity patterns and drivers for taxonomic and functional beta diversity. Specifically, taxonomic beta diversity was mainly driven by the turnover component affected by spatial processes, whereas functional beta diversity was dominated by the nestedness component affected by environmental processes. Furthermore, our analysis of the division of the whole communities demonstrated that the varying responses of benthic diatoms with different attached abilities to environmental filtering, dispersal limitation, and directional flow were the essential reasons for shaping the biodiversity patterns of species turnover and functional nestedness in the alpine stream. Our findings suggested that partitioning beta diversity and dividing the entire community can more deeply infer underlying community assembly processes, thereby providing valuable insights into understanding biodiversity patterns, drivers, and conservation strategies.

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Coronavirus infectious disease 2019 (COVID-19), caused by severe acute respiratory virus type 2 (SARS-CoV-2), has caused a global public health crisis. As an RNA virus, the high gene mutability of SARS-CoV-2 poses significant challenges to the development of broad-spectrum vaccines and antiviral therapeutics. There remains a lack of specific therapeutics directly targeting SARS-CoV-2. With the ability to efficiently inhibit the expression of target genes in a sequence-specific way, small interfering RNA (siRNA) therapy has exhibited significant potential in antiviral and other disease treatments. In this work, we presented a highly effective self-assembled siRNA nanoparticle targeting multiple highly conserved regions of SARS-CoV-2. The siRNA sequences targeting viral conserved regions were first screened and evaluated by their thermodynamic features, off-target effects, and secondary structure toxicities. RNA motifs including siRNA sequences were then designed and self-assembled into siRNA nanoparticles. These siRNA nanoparticles demonstrated remarkable uniformity and stability and efficiently entered cells directly through cellular endocytic pathways. Moreover, these nanoparticles effectively inhibited the replication of SARS-CoV-2, exhibiting a superior inhibitory effect compared to free siRNA. These results demonstrated that these self-assembled siRNA nanoparticles targeting highly conserved regions of SARS-CoV-2 represent highly effective antiviral candidates for the treatment of infections, and are promisingly effective against current and future viral variants.

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OBJECTIVE: To review the current approaches to the diagnosis of Post-Thrombotic Syndrome (PTS) and to evaluate the potential need for a diagnostic tool. METHOD: Medical specialists were invited to participate in an online survey of their current approaches to the diagnosis and management of PTS, including the use of scoring systems, diagnostic imaging techniques and the extent the practitioner reviews the patient's venous history. RESULTS: 502 participants completed the survey. Over 80% obtained imaging reports to confirm a history of deep vein thrombosis (DVT). 72% of participants always obtained an up-to-date duplex ultrasound for PTS diagnosis. Over 50% did not use a scoring system for either PTS diagnosis or management. 65% of the participants agreed that a new system for PTS diagnosis should be devised. CONCLUSION: Heterogeneity was observed in methods of diagnosing PTS by medical practitioners with frequent use of medical imaging studies and moderate use of scoring systems. Development of a new diagnostic tool for PTS should be considered for future studies.

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BACKGROUND: Caspofungin is an echinocandin antifungal agent commonly used as the first-line therapy for invasive candidiasis, salvage therapy for invasive aspergillosis, and empirical therapy for presumed fungal infections. Pharmacokinetic (PK) variabilities and suboptimal exposure have been reported for caspofungin, increasing the risk of insufficient efficacy. OBJECTIVE: This work aimed to develop a caspofungin population pharmacokinetic (popPK) library and demonstrate its utility by assessing the probability of target attainment across diverse settings. METHODS: We established a caspofungin popPK model library following a rigorous literature review, re-implementing selected models in R with rxode2. Quality control procedures included a comparison of different studies and assessing covariate impacts. Model libraries were primarily used to perform Monte Carlo simulations to estimate target attainment and guide personalized dosing in Candida infections. RESULTS: A total of 13 models, one- or two-compartment models, were included. The most significant covariates were body size (weight and body surface area), liver function, and albumin level. The results show that children and adults showed considerable differences in pharmacokinetics. For C. albicans and C. parapsilosis, none of the populations achieved a PTA of ≥90% at their respective susceptible MIC values. In contrast, for C. glabrata, 70% of the adult studies reached a PTA of ≥90%, while all pediatric studies achieved the same PTA level. CONCLUSION: At the recommended dosage, adult patients showed notably lower exposure to caspofungin compared to pediatric patients. Considering body size, liver function, and serum albumin is crucial when determining caspofungin dosage regimens. Furthermore, further research is required to comprehensively understand the pharmacokinetics of caspofungin in pediatric patients.

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The protection of plants in mountainous and hilly areas differs from that in plain areas due to the complex terrain, which divides the work plot into many narrow plots. When designing the path planning method for plant protection UAVs, it is important to consider the generality in different working environments. To address issues such as poor path optimization, long operation time, and excessive iterations required by traditional swarm intelligence algorithms, this paper proposes a bionic three-dimensional path planning algorithm for plant protection UAVs. This algorithm aims to plan safe and optimal flight paths between work plots obstructed by multiple obstacle areas. Inspired by krill group behavior and based on group intelligence algorithm theory, the bionic three-dimensional path planning algorithm consists of three states: "foraging behavior", "avoiding enemy behavior", and "cruising behavior". The current position information of the UAV in the working environment is used to switch between these states, and the optimal path is found after several iterations, which realizes the adaptive global and local convergence of the track planning, and improves the convergence speed and accuracy of the algorithm. The optimal flight path is obtained by smoothing using a third-order B-spline curve. Three sets of comparative simulation experiments are designed to verify the performance of this proposed algorithm. The results show that the bionic swarm intelligence algorithm based on krill swarm behavior reduces the path length by 1.1~17.5%, the operation time by 27.56~75.15%, the path energy consumption by 13.91~27.35%, and the number of iterations by 46~75% compared with the existing algorithms. The proposed algorithm can shorten the distance of the planned path more effectively, improve the real-time performance, and reduce the energy consumption.