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.

Objective To investigate the role of Toll-like receptor 4(TLR4)in the regulation of homocys-teine(Hcy)-induced ferroptosis in macrophages.Methods Mouse macrophage cells RAW264.7 were cultured and divided into control group,Hcy intervention group(Hcy group),and Hcy plus ferroptosis inhibitor group(Hcy+Fer-1 group).After transfection with interference fragments,macrophages were treated with Hcy,and then divided into control group,Hcy intervention group(Hcy group),TLR4 interference negative control plus Hcy intervention group(si-NC+Hcy group),and TLR4 interference plus Hcy intervention group(si-TLR4+Hcy group).Macrophages were transfected with overexpression lentivirus and treated with Hcy,then were divided into control group,Hcy intervention group(Hcy group),a TLR4 overexpression negative control plus Hcy intervention group(OE-NC+Hcy group),and a TLR4 overexpression plus Hcy intervention group(OE-TLR4+Hcy group).After 48 hours of intervention,real-time fluorescent quantitative PCR and western blot were used to detect the expression levels of TLR4 in macrophages treated with Hcy;western blot was used to detect the expression levels of ferroptosis-related proteins ACSL4,GPX4,and FTH1 in macrophages,and ferrous ion assay kit to detect the concentration of Fe2+in macrophages;reactive oxygen species(ROS)assay kit and laser confocal microscopy were used to detect the content of intracellular reactive oxygen species.Results Compared with those in the control group,the expression level of the pro-ferroptosis protein ACSL4 was increased in the Hcy group(P<0.05),while the expression levels of anti-ferroptosis proteins GPX4 and FTH1 were decreased(P<0.05);the concentration of Fe2+was increased(P<0.05),and the content of ROS was increased.Meanwhile,the protein and mRNA expres-sion levels of TLR4 were both increased in the Hcy group(P<0.05).After macrophages were transfected with TLR4 interference fragments,compared with those in the si-NC+Hcy group,the expression levels of GPX4 and FTH1 were increased(P<0.05);the expression level of ACSL4 was decreased(P<0.05);the concentration of Fe2+was decreased(P<0.05),and the content of ROS was reduced in the si-TLR4+Hcy group.After macro-phages were transfected with TLR4 overexpression lentivirus,compared with those in the OE-NC+Hcy group,the expression levels of GPX4 and FTH1 were decreased(P<0.05),and the expression level of ACSL4 was increased(P<0.05)in the OE-TLR4+Hcy group.Conclusion Hcy induces the occurrence of ferroptosis in macrophages,and Toll-like receptor 4 has a positive feedback regulatory effect on ferroptosis in macrophages.

Objective To investigate the role of Toll-like receptor 4(TLR4)in the regulation of homocys-teine(Hcy)-induced ferroptosis in macrophages.Methods Mouse macrophage cells RAW264.7 were cultured and divided into control group,Hcy intervention group(Hcy group),and Hcy plus ferroptosis inhibitor group(Hcy+Fer-1 group).After transfection with interference fragments,macrophages were treated with Hcy,and then divided into control group,Hcy intervention group(Hcy group),TLR4 interference negative control plus Hcy intervention group(si-NC+Hcy group),and TLR4 interference plus Hcy intervention group(si-TLR4+Hcy group).Macrophages were transfected with overexpression lentivirus and treated with Hcy,then were divided into control group,Hcy intervention group(Hcy group),a TLR4 overexpression negative control plus Hcy intervention group(OE-NC+Hcy group),and a TLR4 overexpression plus Hcy intervention group(OE-TLR4+Hcy group).After 48 hours of intervention,real-time fluorescent quantitative PCR and western blot were used to detect the expression levels of TLR4 in macrophages treated with Hcy;western blot was used to detect the expression levels of ferroptosis-related proteins ACSL4,GPX4,and FTH1 in macrophages,and ferrous ion assay kit to detect the concentration of Fe2+in macrophages;reactive oxygen species(ROS)assay kit and laser confocal microscopy were used to detect the content of intracellular reactive oxygen species.Results Compared with those in the control group,the expression level of the pro-ferroptosis protein ACSL4 was increased in the Hcy group(P<0.05),while the expression levels of anti-ferroptosis proteins GPX4 and FTH1 were decreased(P<0.05);the concentration of Fe2+was increased(P<0.05),and the content of ROS was increased.Meanwhile,the protein and mRNA expres-sion levels of TLR4 were both increased in the Hcy group(P<0.05).After macrophages were transfected with TLR4 interference fragments,compared with those in the si-NC+Hcy group,the expression levels of GPX4 and FTH1 were increased(P<0.05);the expression level of ACSL4 was decreased(P<0.05);the concentration of Fe2+was decreased(P<0.05),and the content of ROS was reduced in the si-TLR4+Hcy group.After macro-phages were transfected with TLR4 overexpression lentivirus,compared with those in the OE-NC+Hcy group,the expression levels of GPX4 and FTH1 were decreased(P<0.05),and the expression level of ACSL4 was increased(P<0.05)in the OE-TLR4+Hcy group.Conclusion Hcy induces the occurrence of ferroptosis in macrophages,and Toll-like receptor 4 has a positive feedback regulatory effect on ferroptosis in macrophages.

Objective To investigate the frequency of staging behaviors involved in intimate partner homicide cases,as well as their correlation with the nature of death,medico-legal characteristics,and their correspondence with real causes of death.In order to improve the forensic understanding of staging behaviors in intimate partner homicide cases.Methods Using 100 investigated intimate homicides,forensic elements were statistically analyzed.The Chi square test was used to analyze the correlation between staging behavior and intimate partners,cause of death,injury weapons,time of death,degree of injury,resistance injury,postmortem intervals,and other specific elements and the occurrence of staging behavior.The corresponding partner between staging cause of death and real cause of death was clarified.Results Among the 100 intimate partner homicides,22 involved staging behaviors.Out of 10 cases of"staging"suicide,6 cases(60%)were attributed to staged causes of death.Among the 12"accidental"cases,there were 10 cases(83.33%)of staged causes of death.Staging manner of death appeared in 3 cases(30%)of"suicide"cases,and there was only one in"accidental"case(8.3%).The proportion of staged causes of death in strangulation cases was relatively high(35.71%,10/28).In cases with mild damage,the proportion of staging causes of death is higher(15/46).In cases without defense injuries,the proportion of staged causes of death was 23.19%(16/69).Among the true causes of death,strangulation in homicide was most commonly staged.Conclusion Different relationships of intimate partners did not affect the occurrence and distribution of staging behaviors.In cases involving staging behavior,the number of cases with staging as"accidental"nature of death is higher than that of"suicide"cases.The deaths with minor surface injuries such as strangulation and poisoning can be easily staging as suicide or accident.

Objective To investigate the frequency of staging behaviors involved in intimate partner homicide cases,as well as their correlation with the nature of death,medico-legal characteristics,and their correspondence with real causes of death.In order to improve the forensic understanding of staging behaviors in intimate partner homicide cases.Methods Using 100 investigated intimate homicides,forensic elements were statistically analyzed.The Chi square test was used to analyze the correlation between staging behavior and intimate partners,cause of death,injury weapons,time of death,degree of injury,resistance injury,postmortem intervals,and other specific elements and the occurrence of staging behavior.The corresponding partner between staging cause of death and real cause of death was clarified.Results Among the 100 intimate partner homicides,22 involved staging behaviors.Out of 10 cases of"staging"suicide,6 cases(60%)were attributed to staged causes of death.Among the 12"accidental"cases,there were 10 cases(83.33%)of staged causes of death.Staging manner of death appeared in 3 cases(30%)of"suicide"cases,and there was only one in"accidental"case(8.3%).The proportion of staged causes of death in strangulation cases was relatively high(35.71%,10/28).In cases with mild damage,the proportion of staging causes of death is higher(15/46).In cases without defense injuries,the proportion of staged causes of death was 23.19%(16/69).Among the true causes of death,strangulation in homicide was most commonly staged.Conclusion Different relationships of intimate partners did not affect the occurrence and distribution of staging behaviors.In cases involving staging behavior,the number of cases with staging as"accidental"nature of death is higher than that of"suicide"cases.The deaths with minor surface injuries such as strangulation and poisoning can be easily staging as suicide or accident.

Objective:To investigate the application value of cystic plate approach (CPA) for extrahepatic right hepatic pedicle dissection in minimally invasive anatomical hepatectomy (MIALR).Methods:The retrospective cohort study was conducted. The clinicopathological data of 42 patients with primary liver cancer who underwent laparoscopic right hemi-hepatectomy in Nanfang Hospital of Southern Medical University from August 2020 to August 2022 were collected. There were 36 males and 6 females, aged (55±13)years. Of the 42 patients, 25 cases undergoing CPA for extrahepatic right hepatic pedicle dissection were divided into the CPA group, and 17 cases undergoing traditional approach for extrahepatic right hepatic pedicle dissection were divided into the traditional approach group. Observation indicators: (1) surgical situations; (2) postoperative situations. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( IQR), and comparison between groups was conducted using the Mann?Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi?square test or Fisher exact probability. Comparison of ordinal data was conducted using the non‐parameter rank sum test. Results:(1) Surgical situations. All patients in the two groups underwent laparoscopic right hemi-hepatectomy successfully, with the surgical margin as negative. The operative time, volume of intraoperative blood loss, time of dissection of the targeted hepatic pedicle, cases undergoing dissection of the trunk of right anterior hepatic pedicle and its operation time, cases undergoing dissection of the trunk of right posterior hepatic pedicle and its operation time, cases with hepatic pedicle injury, cases with hepatic tissue injury, cases with dissection space as large and small were 150.00(130.00)minutes, 100.00(100.00)mL, 472.00(201.00)seconds, 10 and 366.00(94.75)seconds, 9 and 564.00(138.50)seconds, 2, 2, 25, 0 in patients of the CPA group, versus 140.00(113.00)minutes, 100.00(125.00)mL, 670.00(107.00)seconds, 8 and 663.00(136.00)seconds, 7 and 783.00(189.00)seconds, 8, 5, 2, 19 in patients of the traditional approach group. There were significant differences in the time of dissection of the targeted hepatic pedicle, time of dissection of the trunk of right anterior hepatic pedicle, time of dissection of the trunk of right posterior hepatic pedicle, hepatic tissue injury, dissection space between the two groups ( Z=-4.809, -3.254, -3.188, χ2=6.493, 34.314, P<0.05) and there was no significant difference in the operation time, volume of intraoperative blood loss, dissection of the trunk of right anterior hepatic pedicle, dissection of the trunk of right posterior hepatic pedicle, hepatic tissue injury between the two groups ( Z=-0.282, -0.412, χ2=0.095, 0.002, 1.976, P>0.05). (2) Postoperative situations. There was no patient undergoing postoperative hemorrhage in both of the two groups. The alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBil) and prothrombin time (PT) at postoperative day 3, cases with postoperative biliary fistula, pathological type of tumor (hepatocellular carcinoma, intrahepatic cholangiocarcinoma) were 68.00(48.50)U/L, 52.00(35.50)U/L, 28.30(12.35)mmol/L, 12.40(2.40)seconds, 2, 21, 4 in patients of the CPA group. The above indicators were 58.00(25.00)U/L, 41.00(19.50)U/L, 26.80(14.25)mmol/L, 12.50(2.95)seconds, 5, 15, 2 in patients of the traditional approach group. There was no significant difference in the ALT, AST, TBil, PT at postoperative day 3, cases with postoperative biliary fistula between the two groups ( Z=-1.218, -1.488, -0.205, -0.320, χ2=1.976, P>0.05), and there was no significant difference in the pathological type of tumor between the two groups ( P>0.05). Conclusion:Application of CPA for extrahepatic right hepatic pedicle dissection in MIALR is safe and feasible.

Objective:To investigate the application value of cystic plate approach (CPA) for extrahepatic right hepatic pedicle dissection in minimally invasive anatomical hepatectomy (MIALR).Methods:The retrospective cohort study was conducted. The clinicopathological data of 42 patients with primary liver cancer who underwent laparoscopic right hemi-hepatectomy in Nanfang Hospital of Southern Medical University from August 2020 to August 2022 were collected. There were 36 males and 6 females, aged (55±13)years. Of the 42 patients, 25 cases undergoing CPA for extrahepatic right hepatic pedicle dissection were divided into the CPA group, and 17 cases undergoing traditional approach for extrahepatic right hepatic pedicle dissection were divided into the traditional approach group. Observation indicators: (1) surgical situations; (2) postoperative situations. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( IQR), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the non‐parameter rank sum test. Results:(1) Surgical situations. All patients in the two groups underwent laparos-copic right hemi-hepatectomy successfully, with the surgical margin as negative. The operation time, volume of intraoperative blood loss, time of dissection of the targeted hepatic pedicle, cases under-going dissection of the trunk of right anterior hepatic pedicle and its operation time, cases under-going dissection of the trunk of right posterior hepatic pedicle and its operation time, cases with hepatic pedicle injury, cases with hepatic tissue injury, cases with dissection space as large and small were 150.00(130.00)minutes, 100.00(100.00)mL, 472.00(201.00)seconds, 10 and 366.00(94.75)seconds, 9 and 564.00(138.50)seconds, 2, 2, 25, 0 in patients of the CPA group, versus 140.00(113.00)minutes, 100.00(125.00)mL, 670.00(107.00)seconds, 8 and 663.00(136.00)seconds, 7 and 783.00(189.00)seconds, 8, 5, 2, 19 in patients of the traditional approach group. There were significant differences in the time of dissection of the targeted hepatic pedicle, time of dissection of the trunk of right anterior hepatic pedicle, time of dissection of the trunk of right posterior hepatic pedicle, hepatic pedicle injury, dissection space between the two groups ( Z=-4.809, -3.254, -3.188, χ2=6.493, 34.314, P<0.05) and there was no significant difference in the operation time, volume of intraoperative blood loss, dissection of the trunk of right anterior hepatic pedicle, dissection of the trunk of right posterior hepatic pedicle, hepatic tissue injury between the two groups ( Z=-0.282, -0.412, χ2=0.095, 0.002, 1.976, P>0.05). (2) Postoperative situations. There was no patient under-going postoperative hemorrhage in both of the two groups. The alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBil) and prothrombin time (PT) at postoperative day 3, cases with postoperative biliary fistula, pathological type of tumor (hepatocellular carcinoma, intrahepatic cholangiocarcinoma) were 68.00(48.50)U/L, 52.00(35.50)U/L, 28.30(12.35)mmol/L, 12.40(2.40)seconds, 2, 21, 4 in patients of the CPA group. The above indicators were 58.00(25.00)U/L, 41.00(19.50)U/L, 26.80(14.25)mmol/L, 12.50(2.95)seconds, 5, 15, 2 in patients of the traditional approach group. There was no significant difference in the ALT, AST, TBil, PT at postoperative day 3, postoperative biliary fistula between the two groups ( Z=-1.218, -1.488, -0.205, -0.320, χ2=1.976, P>0.05), and there was no significant difference in the pathological type of tumor between the two groups ( P>0.05). Conclusion:Application of CPA for extrahepatic right hepatic pedicle dissection in MIALR is safe and feasible.

Background Most of the studies on grading and classification of occupational health compre-hensive risks for specific employers still remain in the establishment and description of methodology, and practical application studies are rarely reported. Objective To explore the application of an occupational disease hazards comprehensive risk assessment method issued by the National Disease Control and Prevention Bureau in conjunction with the National Health Commission and a self-developed occupational health grading and classification method in petroleum refining enterprises, and to provide practical experience for the implementation of differentiated law enforcement by relevant regulatory authorities. Methods Two occupational health grading and classification methods were practiced in three petroleum refining enterprises in Guangdong Province. The occupational hazards comprehensive risk assessment method was provided by the Notice on Carrying out Pilot Work of Occupational Health Classification Supervision and Law Enforcement of the National Disease Control and Prevention Bureau and the National Health Commission. The principle was to derive the occupational health risk level according to nature of occupational hazards, exposure level, and number of workers exposed to them in an employer, and then to classify them into Class A, Class B, and Class C by combining with local occupational health management status level. The occupational health grading and classification method was self-developed according to available domestic and foreign occupational health risk assessment methods. Its principle was to calculate the risk level of each workstation in an employer based on published carcinogenicity classification or LD₅₀/LC₅₀ of chemical toxicants, level of noise, exposure parameters such as exposure level and exposure frequency, estimate the comprehensive risk R_o of the target employer by the Romanian comprehensive risk calculation method, and then calculate a comprehensive risk R_o' weighted by the occupational health management index of the target employer and classify it into class A, class B, and class C. Finally, assessment results, scope of application, inquired indicators, advantages,disadvantages and professional competence requirements of the two grading and classification methods were compared. Results The occupational hazards that were evaluated in three enterprises in this study were benzene, toluene, xylene, gasoline, hydrogen sulfide, and noise. The exposure levels of benzene, toluene, xylene, and gasoline were all below 10% OEL (occupational exposure limit), and hydrogen sulfide and noise were disqualified. Occupational hazards such as benzene and hydrogen sulfide were serious occupational hazards in the three enterprises, and the number of workers exposed was 461, 912, and 224, respectively; the HRs (hazard ratings) of benzene, toluene, xylene, gasoline, hydrogen sulfide, and noise were level 5, 3, 2, 3, 5, and 3 respectively. The occupational health management status of the three enterprises was graded as B, A, and B, respectively by the occupational disease hazards comprehensive risk assessment method. The occupational health management index of the three enterprises was graded as B, A, and A, respectively by the occupational health grading and classification method. The comprehensive risk assessment results showed that two enterprises classified into as the highest class C and one into class B by the occupational disease hazards comprehensive risk assessment method, while all three enterprises were classified into class B by the occupational health grading and classification method. Conclusion The two grading and classification methods are not consistent in the evaluation results of petroleum refining enterprises, and there are differences in the evaluation scope, indicators to be collected, and professionalism. It is recommended that occupational health regulators should fully consider the advantages and disadvantages of the two methods and choose the appropriate assessment method according to the actual regulatory purpose.

Magnetic ferrite nanoparticles (MFNPs) have great application potential in biomedical fields such as magnetic resonance imaging, targeted drugs, magnetothermal therapy and gene delivery. MFNPs can migrate under the action of a magnetic field and target specific cells or tissues. However, to apply MFNPs to organisms, further modifications on the surface of MFNPs are required. In this paper, the common modification methods of MFNPs are reviewed, their applications in medical fields such as bioimaging, medical detection, and biotherapy are summarized, and the future application directions of MFNPs are further prospected.
Ferric Compounds ; Magnetic Resonance Imaging/methods* ; Magnetics ; Magnetite Nanoparticles/therapeutic use* ; Nanoparticles

Objective To establish a SYBR Green real-time PCR detection method with tissue-specific miRNAs and explore a novel approach for forensic body fluid identification. Methods The frequently reported 6 standard miRNAs were synthesized to establish a SYBR Green method, and verify with body fluid. The relative expression data for the 6 miRNAs were obtained using SYBR Green real-time PCR method in peripheral blood, menstrual blood, saliva and semen. Results The assays showed that miRNA205 permitted the unequivocal identification among different fluids. miRNA451 and miRNA144 could be used to distinguish blood from non-blood. Menstrual blood or peripheral blood could be identified through miRNA214. miRNA888 and miRNA891 was highly expressed in semen. Conclusion The results of this study indicate that miRNA SYBR Green profiling may provide a feasible and effective approach to body fluid identification for forensic casework.