The unique characteristics of the deep space environment, microgravity, cosmic radiation, and extreme temperature fluctuations, are emerging as major driving forces for pharmaceutical innovation. These factors provide new avenues for optimizing drug formulations, improving crystal structure quality, and accelerating the discovery of therapeutic targets. Advances in deep space research not only help overcome critical bottlenecks in terrestrial drug development but also promote progress in structure-based drug design and deepen understanding of cellular stress-response mechanisms. Current progress in space-based pharmaceutical research primarily includes the study of disease mechanisms under microgravity, protein crystallization in microgravity, and drug development utilizing deep space radiation and resources. However, the operational complexity, high costs, and limited data reproducibility of space experiments remain key challenges hindering widespread application. Looking ahead, with the integration of automation, artificial intelligence analysis, and on-orbit manufacturing, deep space drug development is expected to achieve greater scalability and precision, opening a new frontier in biopharmaceutical science.
Drug Design ; Drug Development/methods* ; Humans ; Weightlessness ; Space Flight ; Artificial Intelligence ; Extraterrestrial Environment

The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Premature ejaculation refers to a sexual dysfunction in which men experience a short intravaginal ejaculation latency and a lack of control over ejaculation during sexual activity. The onset of this condition is often accompanied by anxiety and depression, which can seriously affect the quality of the patient′s sexual life and the relationship between partners. Based on the "integration of body and spirit" theory in traditional Chinese medicine, our team believes that this condition is a comorbidity of physical and spiritual factors. We propose that the core pathogenesis of this disease lies in the "loss of form and essence, impairment of spirit, and depression of the mind, "while the primary treatment principle involves "nourishing form and regulating spirit." As a result, a new diagnosis and treatment approach of "four-dimensional integration" is summarized in this study. The disease is treated through the four dimensions of shape, body, spirit, and emotion. Traditional Chinese medicine is used to adjust the shape in cases where the physical form is damaged. For individuals with depression of heart and liver qi, the treatment focuses on soothing the heart and smoothing liver qi, and the modified Wangyou Powder and Xuanzhi Decoction is used. In cases where the heart and kidney function are compromised, the treatment involves nourishing both the heart and kidney while restoring interaction between the heart and the kidney, and modified Jihuo Yansi Elixir is used. To reduce the sensitivity of the glans penis, the patient′s body is washed with a traditional Chinese medicine formula, and a delicate fumigation formula is decocted for external washing. For those who are not in tune with their god, psychological counseling can be used to regulate their spirit and advocate "self-partner" and psychotherapy. If there are issues with intimacy, partners should focus on cooperating during foreplay, sexual intercourse, and post-coital interactions. Overall, the treatment aims to harmonize the body and spirit, addressing both physical and psychological factors through a comprehensive, multi-dimensional approach. This method provides new perspectives and ideas for the clinical diagnosis and treatment of this condition.

The liver is one of the essential hubs for maintaining the homeostasis of the organism.Liver aging not only heightens its susceptibility to acute injuries and chronic liver diseases, but also triggers a " chain reaction" of multi-organ aging and dysfunction.With the continuous deepening of the aging population in China, how to prevent, monitor, and evaluate the occurrence, development, and prognosis of liver aging has become an important issue in the field of geriatrics research.Thus, the identification and widespread application of liver aging biomarkers is the key to solving this problem.Therefore, this article reviews the research progress of liver aging-related biomarkers, aiming to provide a basis for the precise prevention and targeted intervention of liver diseases related to aging.

Objective:To analyze the correlation between respiratory event duration and nocturnal oxygen saturation (SpO 2) in adults with obstructive sleep apnea (OSA), and to explore its significance in assessing nocturnal hypoxemia and OSA severity. Methods:A prospective study was conducted on adult OSA patients diagnosed via overnight standard polysomnography (PSG) at the Department of Otolaryngology, First Affiliated Hospital of Sun Yat-sen University from June 2019 to December 2023. Data collected included demographic information, PSG reports, scale scores, and comorbidities. Patients were first stratified by apnea-hypopnea index (AHI) severity. Relationships between respiratory event duration parameters,including total apnea-hypopnea time (TAHT), percentage of total sleep time with apnea-hypopnea (AHT%), total apnea time (TAT), total hypopnea time (THT), and mean apnea-hypopnea time (MAHT), and nocturnal SpO? parameters, including average SpO? (aSpO?), minimal SpO? (mSpO?), mean oxygen desaturation (MOD), and percentage of total sleep time with SpO?<90% (CT90), were analyzed. Patients were then divided into two groups based on the median MAHT (27.6 s) for SpO? comparison. Finally, severe OSA patients were further subclassified using an AHI inflection point (50 events/h) identified via scatter plot analysis to compare nocturnal SpO?. Statistical analysis was performed using SPSS 27.0.Results:Among the 250 study subjects, there were 201 males and 49 females, with ages ranging from 18 to 76 years (mean age: 41.6 ± 11.9 years).TAHT, AHT%, and TAT in OSA patients demonstrated significant negative correlations with aSpO?( r=-0.698, -0.718, -0.646)and mSpO?( r=-0.746, -0.746, -0.748), while showing positive correlations with MOD ( r=0.783, 0.791, 0.823)and CT90 ( r=0.868, 0.866, 0.852), P<0.05. When stratified by MAHT median ( M=27.6 s), the "long-event" subgroup ( n=125) displayed significantly lower mSpO 2 and higher MOD and CT90 compared to the "short-event" subgroup ( n=125), Z=-3.319, 3.288, 2.242; P<0.05. No significant difference in aSpO 2 was observed ( P>0.05). Subgrouping severe OSA patients at AHI=50 events/hour revealed significant differences in aSpO 2, mSpO 2, MOD, and CT90 between groups ( Z=-5.011, -4.787, 5.142, 6.117, P<0.05). Conclusions:TAHT, AHT%, and TAT significantly correlate with nocturnal SpO? parameters in OSA patients and can supplement AHI in assessing OSA severity. MAHT independently reflects nocturnal oxygenation status beyond AHI.

Objective Analysing the risk factors for the occurrence of pre-frailty or frailty of the community elderly in Chengdu and constructing a risk prediction model.Methods The general information questionnaire,MNA-SF scale,Changsha version of the MoCA scale,PSQI scale,FRAIL scale,and Traditional Chinese Medicine Constitution Scale for the elderly were used in the cross-sectional survey.A total of 400 elderly people who completed community physical examinations in Chengdu from April 2022 to April 2023 were selected as the research objects.Based on multivariate Logistic regression analysis,the independent influencing factors were determined,and RStudio software was used to construct a risk prediction model nomogram.The physical examination data of 200 elderly people collected in Deyang City from June 2023 to October 2023 were used for external verification.The area under the ROC curve,Hosmer-Lemeshow test and calibration curve,and decision curve were used to evaluate the discrimination,calibration,and clinical practicability of the model.Results Age,abdominal circumference,number of chronic diseases,PSQI score,allergy history,and balanced constitution were independent influencing factors for pre-frailty/frailty in the elderly in the community(P<0.05),and the regression equation was as follows:Logit(P)=0.063×age+0.025×abdominal circumference-1.006×allergy history+0.300×number of chronic diseases+0.082×PSQI-1.013×balanced constitution-8.269.The area under the ROC curve of the modeling group was 0.779(95%CI:0.733-0.825),the sensitivity was 67.1%,the specificity was 76.3%,and the maximum Youden index was 0.434.The area under the ROC curve of the external validation group was 0.783(95%CI:0.709-0.856),the sensitivity was 62.0%,the specificity was 95.0%,and the maximum Youden index was 0.570.The Hosmer-Lemeshow goodness of fit test results of the two groups were χ2=3.285,P=0.915 and χ2=8.376,P=0.398,and the calibration curve fit was good.DCA showed that the threshold probability of clinical benefit was 5%-99%and 21%-98%.Conclusions The pre-frailty/frailty risk prediction model established in this study has good predictive efficacy for the elderly in the community,and the use of this model for screening and early intervention of high-risk populations can be clinically beneficial.

AIM:To investigate the median effec-tive dose of ciprofol combined with sufentanil to in-hibit tracheal intubation reaction in patients under-going intracranial aneurysm embolization.METH-ODS:Forty-five patients who underwent emboliza-tion for intracranial aneurysms were divided into two groups according to age:non-elderly group(aged 18-64 years)and elderly group(aged＞65 years).Patients in the two groups were first given intravenous ciprofol,of which the initial dose of cip-rofol was 0.4 mg/kg and sufentanil 0.3 μg/kg and rocuronium 0.6 mg/kg were respectively injected according to BIS value and modified observer's as-sessment of alertness and sedation(MOAA/S)score.Then,endotracheal intubation was defined as 3 minutes after the induction of the study drug.Dixon sequential method was adopted,and the dose of ciprofol for the next patient was deter-mined according to whether the tracheal intuba-tion reaction was positive(Positive reaction of tra-cheal intubation was defined as the patient's kino-motor reaction such as coughing during tracheal in-tubation or the increase of MAP or HR within 2 minutes after intubation was greater than 20％of the basic value).When the tracheal intubation indi-cated a positive response,the next patient was raised by one gradient,otherwise,it was lowered by one gradient until the study ended at 7 crosses.The common dose ratio of adjacent patients was 1∶1.1.The Probit probability method was used to cal-culate the 50％effective dose(ED50),95％effective dose(ED95)and the corresponding 95％confidence interval(CI)of ciprofol.Perioperative adverse reac-tions were recorded in both groups.RESULTS:In the non-elderly group,the ED50 of ciprofol inhibit-ing positive tracheal intubation reaction was 0.472 mg/kg(95％CI 0.419-0.565 mg/kg),and the ED95 was 0.567 mg/kg(95％CI 0.513-1.293 mg/kg).In the elderly group,the ED50 of ciprofol inhibiting tra-cheal intubation reaction was 0.409 mg/kg(95％CI 0.383-0.434 mg/kg)and the ED95 was 0.452 mg/kg(95％CI 0.430-0.591 mg/kg).CONCLUSION:The ED50 of ciprofol combined with sufentanil inhibiting positive tracheal intubation reaction was 0.472 mg/kg in non-elderly patients and 0.409 mg/kg in elder-ly patients.

Objective:To investigate the effects of apical periodontitis of mandibular primary molars on the development of mandibu-lar permanent premolars in children in Guangzhou.Methods:335 children aged 4-9 years with apical periodontitis of mandibular pri-molar at one side and normal healthy homologous tooth at another side were included and divided into 2 groups:Group A(n=200)in-cluded the first mandibular premolars and group B(n=135)included the second mandibular premolars.Subgroup A1 and B1 were the apical periodontitis groups,subgroup A2 and B2 were the normal healthy groups.The degree of root destruction of primary teeth,the degree of destruction and development of the dental follicle of permanent teeth,the mesial and distal direction changes,and the eruption height were observed and measured on the panoramic raidiographs,data were statistically analyzed.Results:In the 7-year-old children of A1 and the 6-year-old of B1 groups,the development degree of successor permanent teeth was lower than that of group A2 and group B2 of the same age children respectively(P＜0.05).In the 6-7-year-old children of group A1,the permanent teeth development of boys was slower than that of the girls(P＜0.05).There was no gender difference in dental follicle destruction and malposition of the perma-nent teeth in both A1 and B1 groups(P＞0.05).The proportion of malposition of the successor permanent teeth in group A1 increased with the primary teeth damage degree increace(P＜0.05),while the proportion of malposition of the successor permanent teeth in group B1 showed no significant difference(P＞0.05).Positive correlation between the damage degree of primary teeth and dental follicle of per-manent teeth was observed(rA1=0.41,rB1=0.21,P＜0.05).In boys aged 7-8 years,the succesor permanent teeth eruption in group A1 was higher than that in group A2(P＜0.05),and there was no significant difference between group B1 and group B2(P＞0.05).Conclusion:In the later stages of root stabilization of primary molars,periapical inflammation of primary teeth may cause developmen-tal delay of the succesor permanent teeth,and the delay degree is higher in boys than in girls.With the deterioration of the periapical tissue of primary teeth,the destruction of the dental follicle of permanent teeth may deepen,and the mandibular first premolar is more likely to have abnormal eruption.

Game-based psychological assessment utilizes game mechanisms and elements to enhance partic-ipants'motivation and improve measurement accuracy,but similar to traditional methods,it mainly focuses on static results.By integrating game-based psychological assessment with artificial intelligence technology,this paper propo-ses the paradigm of intelligent psychological assessment based on interactive environment.With analyzing dynamic process data within the game,this paradigm can accurately depict the participants'actions and results in the interac-tive context,more effectively representing individual psychological states and behavioral characteristics.This new paradigm demonstrates advancements and significant potential for development in terms of demand,data collection,and analysis techniques.