Stability, Inheritance, Cross-Resistance, and Fitness Cost of Resistance to λ-Cyhalothrin in Cydia pomonella.

Insecticides are commonly utilized in agriculture and forestry for pest control, but their dispersal can pose hazards to humans and environment. Understanding resistance, inheritance patterns, and fitness costs can help manage resistance. A λ-cyhalothrin-resistant population (LCR) of Cydia pomonella, a global pest of pome fruits and walnuts, was obtained through selective insecticide breeding for 15 generations, showing stable moderate resistance (23.85-fold). This population was cross-resistant to deltamethrin (4.26-fold) but not to ß-cypermethrin, chlorantraniliprole, chlorpyrifos, and avermectin. Genetic analysis revealed the resistance was autosomal, incompletely dominant, and controlled by multiple genes. Increased activity of glutathione S-transferases and cytochrome P450 monooxygenases (P450s) played a primary role in resistance, with specific genes up-regulated in LCR, and exhibited significant expression in midgut. LCR also exhibited fitness costs, including delays in development, reduced fecundity, and slower population growth. These findings contribute to understanding λ-cyhalothrin resistance in C. pomonella and can guide resistance management strategies.

Colchicine prevents perioperative myocardial injury in cardiac surgery by inhibiting the formation of neutrophil extracellular traps: evidence from rat models.

OBJECTIVES: Colchicine, an anti-inflammatory agent, has been reported to improve myocardial infarction prognosis by inhibiting neutrophil extracellular traps release. However, its role in cardiac surgery and the mechanisms behind neutrophil extracellular traps suppression remain unclear. This study aimed to explore colchicine's cardioprotective effects against perioperative myocardial injury in cardiac surgery, focusing on neutrophil extracellular traps inhibition as a novel therapeutic strategy. METHODS: Male Sprague-Dawley rats were pre-treated with colchicine (0.1 mg/kg/day) or CI-amidine (10 mg/kg/day) for seven days before undergoing cardiopulmonary bypass and myocardial ischaemia/reperfusion injury. The model was created by subjecting the rats to cardiopulmonary bypass and myocardial ischaemia/reperfusion injury. Under 4.0% sevoflurane anaesthesia, cardiopulmonary bypass was initiated by cannulating the tail artery and right atrium, and perfusion was maintained for 4 hours. Immunofluorescence detected neutrophil extracellular traps, and Hematoxylin and Eosin staining assessed inflammatory cell. RESULTS: We found colchicine treatment significantly reduced perioperative myocardial injury in rats. Furthermore, we observed a notable elevation of neutrophil extracellular traps in the myocardial tissue of animal models. Moreover, suppressing peptidylarginine deiminase 4(PAD-4) was found to markedly diminish perioperative myocardial injury in rats. Additionally, colchicine can mitigate the release of neutrophil extracellular traps by inhibiting PAD-4. CONCLUSIONS: NETs were significantly elevated during the perioperative period of cardiac surgery. Colchicine significantly mitigated myocardial injury in cardiac surgery by inhibiting neutrophil extracellular traps formation, with PAD-4 inhibition being one of its mechanisms.

Surprising Dynamics Phenomena in the Diels-Alder Reaction of C60 Uncovered with AI.

We performed an extensive artificial intelligence-accelerated quasi-classical molecular dynamics investigation of the time-resolved mechanism of the Diels-Alder reaction of fullerene C60 with 2,3-dimethyl-1,3-butadiene. In a substantial fraction (10%) of reactive trajectories, the larger C60 noncovalently attracts the 2,3-dimethyl-1,3-butadiene long before the barrier so that the diene undergoes the series of complex motions including roaming, somersaults, twisting, and twisting somersaults around the fullerene until it aligns itself to pass over the barrier. These complicated processes could be easily missed in typically performed quantum chemical simulations with shorter and fewer trajectories. After the barrier is passed, the bonds take longer to form compared to the simplest prototypical Diels-Alder reaction of ethene with 1,3-butadiene despite high similarities in transition states and barrier widths evaluated with intrinsic reaction coordinate (IRC) calculations. C60 is mainly responsible for these differences as its reaction with 1,3-butadiene is similar to the reaction with 2,3-dimethyl-1,3-butadiene: the only substantial difference being that the extra methyl groups double the probability of the prolonged alignment phase in dynamics. These additional calculations of C60 with 1,3-butadiene could be performed via active learning more easily by reusing the data generated for the other two reactions, showing the potential for larger-scale exploration of the effects of different substrates in the same types of reactions.

Urinary heavy metals and overall survival of advanced high-grade serous ovarian cancer: A nested case-control study in China.

BACKGROUND: Environmental pollution has emerged as a significant determinant in ovarian cancer prognosis. However, limited evidence exists regarding the correlations between heavy metals and ovarian cancer prognosis. OBJECTIVE: To elucidate the relationship between urinary heavy metals and their mixtures with overall survival (OS) of advanced high-grade serous ovarian cancer (HGSOC). METHODS: Within the Ovarian Cancer Follow-Up Study, we conducted a nested case-control study. A sum of 159 deceased patients and an equal number of alive patients were included, matched by sample date, body mass index, and age at diagnosis. Urinary concentrations of five heavy metals were quantified: arsenic (As), cadmium (Cd), chromium (Cr), mercury (Hg), and lead (Pb). Conditional logistic regression models were employed to calculate odds ratios (ORs) and their 95 % confidence intervals (CIs). To elucidate joint effects, we utilized quantile g-computation and Bayesian kernel machine regression models. RESULTS: For the multivariable adjusted conditional logistic regression model, significant associations were found between high urinary levels of As (OR=1.99, 95 %CI: 1.05-3.79), Cd (OR=2.56, 95 %CI: 1.29-5.05), Hg (OR=2.24, 95 %CI: 1.09-4.62), and Pb (OR=3.80, 95 %CI: 1.75-8.27) and worse OS of HGSOC, comparing the highest tertile to the lowest. Analysis of joint effects showed that elevated concentrations of heavy metal mixtures were related to poor OS of HGSOC. Pb exhibited the highest contribution to the overall association within the metal mixtures. CONCLUSIONS: High urinary heavy metal concentrations were linked to worse OS of HGSOC. Future research is necessary to validate our findings.

Associations between peripheral whole blood cell counts derived indexes and cancer prognosis: An umbrella review of meta-analyses of cohort studies.

Meta-analyses have reported conflicting data on the whole blood cell count (WBCC) derived indexes (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], and lymphocyte-to-monocyte ratio [LMR]) and cancer prognosis. However, the strength and quality of this evidence has not been quantified in aggregate. To grade the evidence from published meta-analyses of cohort studies that investigated the associations between NLR, PLR, and LMR and cancer prognosis. A total of 694 associations from 224 articles were included. And 219 (97.8%) articles rated as moderate-to-high quality according to AMSTAR. There were four associations supported by convincing evidence. Meanwhile, 165 and 164 associations were supported by highly suggestive and suggestive evidence, respectively. In this umbrella review, we summarized the existing evidence on the WBCC-derived indexes and cancer prognosis. Due to the direction of effect sizes is not completely consistent between studies, further research is needed to assess causality and provide firm evidence.

A New Bacterial Strain Producing Both of the Surfactin and Fengycin Lipopeptide Biosurfactant with Strong Emulsifications on Crude Oil.

A new lipopeptide-producing strain Cytobacillus sp. R3-1 was isolated from the production water of the Daqing oilfield in China and identified based on 16S rRNA gene sequence analyses. The strain R3-1 is capable of simultaneously producing both of the surfactin and fengycin, the two major families of the lipopeptide biosurfactant. The chemical structures of the surfactin and fengycin were confirmed by a combination of the ESI-MS, FT-IR, and amino acid analyses, and the impact of various temperatures, pH, and NaCl concentrations on the emulsifying activity (E24) was investigated. The lipopeptide biosurfactant produced by the strain R3-1 exhibited strong emulsifying activity with E24 value over 60% on crude oil and different hydrocarbons, including the cyclohexane, hexadecane, benzene, toluene, kerosene, diesel oil, and liquid paraffin. Meanwhile, it showed excellent emulsifying activity across a broad range of conditions of the temperature up to 60 °C, NaCl tolerance up to 100 g/L, and pH values between 5 and 9, which suggests that the strain R3-1 is a valuable microbial candidate for the simultaneous production of the surfactin and fengycin lipopeptide biosurfactant with strong emulsifying properties and stability under diverse environmental conditions and is a potential application in environmental bioremediation and enhanced oil recovery.

Micro Reference Electrode with an Ultrathin Ionic Path.

Reference electrode (RE) plays the core role in accurate potential control in electrochemistry. However, nanoresolved electrochemical characterization techniques still suffer from unstable potential control of pseudo-REs, because the commercial RE is too large to be used in the tiny electrochemical cell, and thus only pseudo-RE can be used. Therefore, microsized RE with a stable potential is urgently required to push the nanoresolved electrochemical measurements to a new level of accuracy and precision, but it is quite challenging to reproducibly fabricate such a micro RE until now. Here, we revisited the working mechanism of the metal-junction RE and clearly revealed the role of the ionic path between the metal wire and the borosilicate glass capillary to maintain a stable potential of RE. Based on this understanding, we developed a method to fabricate micro ultrastable-RE, where a reproducible ultrathin ionic path can form by dissolving a sandwiched sacrificial layer between the Pt wire and the capillary for the ion transfer. The potential of this new micro RE was almost the same as that of the commercial Ag/AgCl electrode, while the size is much smaller. Different from commercial REs that must be stored in the inner electrolyte, the new RE could be directly stored in air for more than one year without potential drift. Eventually, we successfully applied the micro RE in the electrochemical tip-enhanced Raman spectroscopy (EC-TERS) measurement to precisely control the potential of the working electrode, which makes it possible to compare the results from different laboratories and techniques to better understand the electrochemical interface at the nanoscale.

Free-radical triggered formation of dioxins from 2-chlorophenol pyrolysis investigated by synchrotron radiation photoionization mass spectrometry.

Polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and polychlorinated naphthalenes (PCNs) are a category of highly toxic and environmentally persistent pollutants released particularly via thermal processes of chlorine-containing materials. However, the detailed reaction mechanism, especially the evolution of related radicals remains elusive for decades. Herein we have for the first time characterized the radicals and intermediates during pyrolysis of 2-chlorophenol resulting in PCDD/Fs and PCNs, using a flow tube reactor coupled with in-situ synchrotron radiation photoionization mass spectrometry (SR-PIMS). Transient species including 2-chlorophenoxy (C6H4ClO•), phenoxy (C6H5O•), chloro-cyclopentadienyl (•C5H4Cl), chloro-cyclopentadiene (C5H5Cl), fulvenone ketene (C6H4O) and o-benzyne (o-C6H4), were identified via m/z and photoionization efficiency profile. Potential energy surfaces of the early-stage mechanism and the associated rate constants and branching ratios were elucidated. Successively, the formation mechanisms of PCDD/Fs and PCNs from these transient intermediates at high temperatures were proposed which have experimentally validated and refined the previous mechanism. The results suggested that the combination of 2-chlorophenoxy radicals with another 2-chlorophenoxy, phenoxy, phenyl, or o-benzyne leads to the formation of PCDD/Fs, while PCNs are generated from the self-coupling of chloro-cyclopentadienyl.

Access to Alkenyl Cyclobutanols by Ni-Catalyzed Regio- and Enantio-selective syn-Hydrometalative 4-exo-trig Cyclization of Alkynones.

Enantioselective synthesis of (spiro)cyclobutane derivatives poses significant challenges yet holds promising applications for both synthetic and medicinal chemistry. We report here a nickel-catalyzed asymmetric syn-hydrometalative 4-exo-trig cyclization of alkynones to synthesize alkenyl cyclobutanols with a tetrasubstituted stereocenter. This strategy features a broad substrate scope, delivering a variety of trifluoromethyl-containing rigid (spiro)carbocycle skeletons in good yields and high enantioselectivities (up to 84% yield and 98.5:1.5 er). The synthetic utility is demonstrated through stereospecific transformations into fused spirocycles. Experimental and computational mechanistic studies indicate that the reaction is initiated by an active Ni-H species, with carbonyl-directed hydrometalation as the key for regioselective control. This catalytic method provides a general solution for regioselective hydrofunctionalization of alkynes and represents an efficient reaction pattern for assembling highly strained enantioenriched bioisosteres.

A novel fluorescent sensor for evaluating pH changes in organophosphorus pesticides-treated cells and C. elegans.

pH plays an important role in the evaluation of the healthy status in versatile circumstances. The fluctuation of pH could be affected by complex internal and external stimuli. Especially, the abnormal pH changes is a common characteristic of organophosphorus pesticides (OPs)-caused damage owing to the irreversible inhibition of acetylcholinesterase (AChE) activity. Therefore, the rapid and efficient detection of pH changes is of great significance for predicting the OPs poisoning in living system. However, quick and convenient detecting pH levels in living cells is still limited by the lack of effective chemical tools. Here, a novel fluorescent probe TH-1 based on ESIPT mechanism was synthesized, showing specific fluorescent effects in different pH solutions. Importantly, the AChE catalyzed the hydrolysis product of acetylthiocholine iodide (ATCh) and changed the pH of solution, which influence its fluorescent intensity. Moreover, the probe TH-1 was applied to detecting the pH levels in living cells and C. elegans, providing an efficient chemical sensor for revealing the potential mechanisms of OPs in physiological and pathological processes.

Current perspectives on postoperative cognitive dysfunction in geriatric patients: insights from clinical practice.

Postoperative cognitive dysfunction (POCD) is a common and serious postoperative complication in elderly patients, affecting cognitive function and quality of life. Its pathophysiology is complex, involving age-related cognitive decline, surgical and anesthetic factors, systemic and neuroinflammation, as well as genetic and environmental contributors. Comprehensive preoperative assessment and optimization, the selection of appropriate anesthetic agents, minimally invasive surgical techniques, and early postoperative rehabilitation and cognitive training are effective strategies to reduce the incidence of POCD. Recent research suggests that anti-inflammatory drugs and neuroprotective agents may be promising in preventing POCD. Additionally, non-pharmacological interventions, including cognitive and physical training, have shown positive effects. Future research directions should include large-scale clinical trials and mechanistic studies to further understand and manage POCD, along with integrating new findings into clinical practice. Continuous education and training for healthcare professionals are essential to ensure the effective application of the latest research findings in patient care. Through multidisciplinary collaboration and ongoing improvements, these efforts can significantly enhance the cognitive function and quality of life of elderly surgical patients.

Characteristics and Significance of Tertiary Lymphoid Structures Based on Molecular Subtypes in Endometrial Cancer.

The purpose of this study is to investigate the characteristics and significance of tertiary lymphoid structures (TLSs) in endometrial cancer (EC) based on molecular subtypes. A total of 220 patients with EC were retrospectively enrolled, including 20 with polymerase epsilon ultramutated (POLE-mut), 63 with mismatch repair deficient, 32 with p53 abnormal, and 105 with no specific molecular profile. The presence and maturity of TLSs were determined by immunohistochemical markers (CD3, CD20, CD21, and Bcl6). Disease-free survival served as the endpoint event. TLSs were found in 91 out of 220 patients (41.1%), with 68 located in peritumoral tissues and 37 exhibiting well-formed germinal center structures. The presence and different maturity of TLSs were closely associated with tumor-infiltrating lymphocytes and the programmed cell death ligand-1 expression. Moreover, TLSs displayed heterogeneity across different molecular subtypes. Notably, the TLSs, tumor-infiltrating lymphocytes, and expression of the programmed cell death ligand-1 were significantly enriched in POLE-mut EC. Multivariate logistic regression analysis showed the presence of TLSs (odds ratio: 3.483, 95% CI: 1.044-11.623, P = 0.042) as a potential predictor of POLE-mut EC. Kaplan-Meier survival curves revealed that molecular subtypes significantly stratified prognosis in patients with EC (P = 0.002), whereas TLSs did not. Multivariate Cox regression analysis indicated that The International Federation of Gynecology and Obstetrics stage and Ki-67 expression were independent prognostic factors affecting disease-free survival in patients with EC, and TLSs were not included. In conclusion, TLSs in EC exhibit heterogeneity based on molecular subtypes, necessitating further exploration to determine their clinical application value.

Reverse hierarchical DED assembly in the cFLIP-procaspase-8 and cFLIP-procaspase-8-FADD complexes.

cFLIP, a master anti-apoptotic regulator, targets the FADD-induced DED complexes of procaspase-8 in death receptor and ripoptosome signaling pathways. Several tumor cells maintain relatively high levels of cFLIP in achieving their immortality. However, understanding the three-dimensional regulatory mechanism initiated or mediated by elevated levels of cFLIP has been limited by the absence of the atomic coordinates for cFLIP-induced DED complexes. Here we report the crystal plus cryo-EM structures to uncover an unconventional mechanism where cFLIP and procaspase-8 autonomously form a binary tandem DED complex, independent of FADD. This complex gains the ability to recruit FADD, thereby allosterically modulating cFLIP assembly and partially activating caspase-8 for RIPK1 cleavage. Our structure-guided mutagenesis experiments provide critical insights into these regulatory mechanisms, elucidating the resistance to apoptosis and necroptosis in achieving immortality. Finally, this research offers a unified model for the intricate bidirectional hierarchy-based processes using multiprotein helical assembly to govern cell fate decisions.

Prognostic value of three clinical nutrition scoring system (NRI, PNI, and CONUT) in elderly patients with prostate cancer.

Background: Most of patients with prostate cancer (PCa) are elderly and have a long course of disease. Preoperative assessment of the patient's clinical nutritional status facilitates early intervention and improves patient prognosis. Methods: We assessed the nutritional status of PCa patients utilizing the Nutritional Risk Index (NRI), Prognostic Nutritional Index (PNI), and Controlling Nutritional Status (CONUT) scoring systems. Survival comparisons between groups were conducted using Kaplan-Meier curve analysis and log-rank tests, while Cox proportional hazards regression analysis was employed to identify independent prognostic factors. Furthermore, we implemented bootstrap-based optimism correction methods to validate the scoring systems and applied decision curve analysis to evaluate the non-inferiority of these three clinical nutrition scoring systems relative to the conventional American Joint Committee on Cancer (AJCC) staging. Results: In this study, malnutrition was diagnosed in 31.51% of the patients using the NRI, 13.02% using the PNI, and 88.28% using the CONUT score. After adjusting for confounders, normal nutritional status as defined by NRI and PNI emerged as an independent prognostic factor for prostate-specific antigen progression-free survival (PSA-PFS). However, nutritional status assessed by CONUT inaccurately predicted PSA-PFS. Normal nutritional status, as determined by all three scoring systems, was found to be an independent prognostic factor for progression-free survival (PFS). Following adjustments for optimistic estimates, the C-index for NRI in predicting both PSA-PFS and PFS remained the highest among the three scoring systems. The results of the DCA indicated that the C-index of all three scoring systems was higher than that of AJCC stage. Conclusions: NRI, PNI, and CONUT are convenient and clinically applicable scoring systems. A clinical malnutrition intervention may improve the prognosis of prostate cancer patients.

Comparison of the short- and long-term effects of zinc ions on the anaerobic mesophilic co-digestion of food waste and waste activated sludge: Digester performance, antibiotic resistance gene reduction and the microbial community.

Heavy metals contained in waste activated sludge (WAS), especially zinc ions, have an inhibitory effect on the anaerobic digestion. However, the effects of zinc ions on digester performance, antibiotic resistance genes (ARGs) reduction, and the microbial community involved in the anaerobic mesophilic co-digestion (AcoD) of WAS and food waste (FW) have not been fully characterized. Therefore, batch trials and continuous stirred tank reactors were used under different zinc-ion concentrations. Findings showed that the AcoD system can tolerate a maximum zinc ion of 540 mg/L in a short-term batch and 470 mg/L in a long-term AcoD system, promoting methane production of approximately 1.0-17.0 %. Metagenomic analysis revealed that syntrophic H2 transfer occurred between Syntrophomonas and Methanoculleus and the aceticlastic and hydrogenotrophic methanogenic pathways were both enhanced by 1.18- and 1.16 times, respectively. Moreover, the relative abundance of Methanosarcina increased from 58.4 % to 72.5 % at 470 mg/L to adapt to the high zinc ion concentration during long-term continuous operation. These results revealed that AcoD with a low zinc ion concentration can effectively increase the removal percentage of ARGs. The results provide guidance for biogas recovery and use of mesophilic AcoD with FW and WAS containing high zinc ion concentrations without pretreatment process.

Post­recovery symptoms of infected cases after Omicron pandemic: a quick online cross-sectional study based on C19-YRSm in China.

BACKGROUND: The post COVID-19 health condition of Chinese residents infected with Omicron is not clear after the change of epidemic prevention policies. This study aimed to clarify the epidemiology and associated factors about health status of rehabilitation patients. METHODS: A quick questionnaire study based on C19-YRSm was conducted in mainland China through internet from May 1, 2023, to May 7, 2023. Chinese native speakers infected with Omicron variant agreed to participate were included. Persisting symptom and living habits were simultaneously inquired. Logistic regression analysis was used to identify the associated factors. RESULTS: In this study 753 individuals were included. Of whom 57.90% were males, 89.38% did not seek medical service, 99.47% recovered within less than 120 days. Breathlessness (47.68%), cognitive impairment (44.89%), Anxiety/mood changes (33.20%), pain/discomfort (32.94%), fatigue or tiredness not improved by rest (32.27%) and post-exertional malaise (30.01%) were the top reported key symptoms. Less than 10% respondents reported functional limitations. The prevalence of fever was reported greater than that of other symptoms, with dry eyes at 14.87%, appetite change at 14.34%, and hair loss at 12.22%. Middle age (OR: 2.353, 95%CI: 1.171 ~ 4.729), underlying diseases (OR: 2.293, 95%CI: 1.216 ~ 4.324), severe key symptom (OR: 6.168, 95%CI: 1.376 ~ 27.642) and at least one other symptom (OR: 1.847, 95%CI: 1.225 ~ 2.718)during the recovery were the risk factors of poor overall health after infection (current overall health score <8; 74.10%), while daily exercise in recovery period (OR: 0.457, 95%CI: 0.229 ~ 0.913), a low-fat diet (OR: 0.600, 95%CI: 0.401 ~ 0.898) and the recovery time from 2 to 4 months (OR: 0.639, 95%CI: 0.445 ~ 0.918) were the protective factors. CONCLUSION: This is the first time to use the C19-YRSm scale to evaluate the health status in China. The study revealed prevalence of persistent symptoms within 120 days after Omicron onset.

Draft genome sequence data of Pythium cedri Chen 4, the causal pathogen of deodar cedar root rot.

Pythium species are distributed globally, with certain members playing significant roles as plant and animal pathogens. Pythium cedri Chen 4 has been identified as a pathogenic isolate responsible for causing root rot on Cedrus deodara. Here, a comprehensive genome-wide sequence of P. cedri strain Chen 4 utilizing the Illumina NovaSeq sequencing platform and a Pacific Biosciences Sequel sequencing platform is presented. The genome of P. cedri strain Chen 4 was assembled into 150 contigs containing a combined size of 41.25 Mb, N50 value of 1,717,859 bp and N90 value of 431,829 bp. Genome annotation revealed 14,077 protein-encoding genes and 364 of the 1016 predicted proteins were putative effectors. The present work enriches the genetic resources of P. cedri for studying its evolution and can contribute to a better understanding of P. cedri-host interaction.

The role of epigenetics in women's reproductive health: the impact of environmental factors.

This paper explores the significant role of epigenetics in women's reproductive health, focusing on the impact of environmental factors. It highlights the crucial link between epigenetic modifications-such as DNA methylation and histones post-translational modifications-and reproductive health issues, including infertility and pregnancy complications. The paper reviews the influence of pollutants like PM2.5, heavy metals, and endocrine disruptors on gene expression through epigenetic mechanisms, emphasizing the need for understanding how dietary, lifestyle choices, and exposure to chemicals affect gene expression and reproductive health. Future research directions include deeper investigation into epigenetics in female reproductive health and leveraging gene editing to mitigate epigenetic changes for improving IVF success rates and managing reproductive disorders.

Efficacy of antimicrobial peptide P113 oral health care products on the reduction of oral bacteria number and dental plaque formation in a randomized clinical assessment.

Background/purpose: Dental plaque is the main cause leading to the dental caries and periodontal diseases. The main purpose of this study was to test the efficacy of oral spray containing the antimicrobial peptide P-113 on the reduction of oral bacteria number and dental plaque formation in a randomized clinical assessment. Materials and methods: This study was divided into two parts. In Part A, we investigated the user experiences with the P-113 containing oral spray. In part B, 14 subjects in the experimental group used the P-113-containing oral spray, while 14 subjects in the control group used a placebo without the P-113 in a 4-week clinical trial. Participants were asked to use the P-113-containing oral spray or placebo 3 times per day and 5 times per use. Moreover, 3 check-ups and 2 washouts were carried out to evaluate the DMFT score, dental plaque weight, dental plaque index, and gingival index. Results: In part A, up to 91.8% of the subjects in the experimental group were satisfied with the use of the P-113-containing oral spray. In part B, based on our PacBio SMRT sequencing platform and DADA2 analysis, the numbers of Streptococcus and Porphyromonas in the experimental group were lower than those in the control group. In addition, decreased dental plaque weight, dental plaque index, and gingival index were all observed in the experimental group. Conclusion: The P-113-containing oral spray has the potential to reduce the dental caries and periodontal disease-related bacteria and to control the dental plaque formation.

Cardiovascular adaptations and pathological changes induced by spaceflight: from cellular mechanisms to organ-level impacts.

The advancement in extraterrestrial exploration has highlighted the crucial need for studying how the human cardiovascular system adapts to space conditions. Human development occurs under the influence of gravity, shielded from space radiation by Earth's magnetic field, and within an environment characterized by 24-hour day-night cycles resulting from Earth's rotation, thus deviating from these conditions necessitates adaptive responses for survival. With upcoming manned lunar and Martian missions approaching rapidly, it is essential to understand the impact of various stressors induced by outer-space environments on cardiovascular health. This comprehensive review integrates insights from both actual space missions and simulated experiments on Earth, to analyze how microgravity, space radiation, and disrupted circadian affect cardiovascular well-being. Prolonged exposure to microgravity induces myocardial atrophy and endothelial dysfunction, which may be exacerbated by space radiation. Mitochondrial dysfunction and oxidative stress emerge as key underlying mechanisms along with disturbances in ion channel perturbations, cytoskeletal damage, and myofibril changes. Disruptions in circadian rhythms caused by factors such as microgravity, light exposure, and irregular work schedules, could further exacerbate cardiovascular issues. However, current research tends to predominantly focus on disruptions in the core clock gene, overlooking the multifactorial nature of circadian rhythm disturbances in space. Future space missions should prioritize targeted prevention strategies and early detection methods for identifying cardiovascular risks, to preserve astronaut health and ensure mission success.