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.

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 explore the CT and MRI manifestation of salivary gland mucosa-associated lymphoid tissue(MALT)lymphoma.Methods The preoperative CT and MRI images of 89 patients with salivary gland MALT lymphoma who were confirmed by surgical pathology were analyzed retrospectively.Results Salivary gland MALT lymphoma were mainly located in the parotid gland(64 cases,71.9％).The ratio of male to female was 1 ≤ 5.Sixty-nine cases(77.5％)showed concomitant Sjogren's syndrome(SS).Typical imaging findings were round or lobulated well-marginated solid masses with moderate to severe enhancement.Atypical imaging findings were all from parotid gland MALT lymphoma,including cyst-solid mixed masses(34 cases,38.2％),poorly marginated boundaries(9 cases,10.1％),and punctuate calcification(5 cases,5.6％).The average apparent diffusion coefficient(ADC)value of lesions was(0.59±0.09)× 10-3 mm2/s and the time-signal intensity curve(TIC)type was mainly type Ⅱ(66.7％).Conclusion Salivary gland MALT lymphoma exhibits certain clinical and imaging characteristics.But when occur in parotid gland,some lesions may present atypically,which require diagnosis with the aid of functional MRI.

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 explore the CT and MRI manifestation of salivary gland mucosa-associated lymphoid tissue(MALT)lymphoma.Methods The preoperative CT and MRI images of 89 patients with salivary gland MALT lymphoma who were confirmed by surgical pathology were analyzed retrospectively.Results Salivary gland MALT lymphoma were mainly located in the parotid gland(64 cases,71.9％).The ratio of male to female was 1 ≤ 5.Sixty-nine cases(77.5％)showed concomitant Sjogren's syndrome(SS).Typical imaging findings were round or lobulated well-marginated solid masses with moderate to severe enhancement.Atypical imaging findings were all from parotid gland MALT lymphoma,including cyst-solid mixed masses(34 cases,38.2％),poorly marginated boundaries(9 cases,10.1％),and punctuate calcification(5 cases,5.6％).The average apparent diffusion coefficient(ADC)value of lesions was(0.59±0.09)× 10-3 mm2/s and the time-signal intensity curve(TIC)type was mainly type Ⅱ(66.7％).Conclusion Salivary gland MALT lymphoma exhibits certain clinical and imaging characteristics.But when occur in parotid gland,some lesions may present atypically,which require diagnosis with the aid of functional MRI.

Osteocytes are the most abundant and long-lived cells in bone,serving as primary regulators of bone remodeling.Besides playing critical roles in endocrine regulation and calcium-phosphate metabolism,osteocytes are primary responders to mechanical stimuli,perceiving and responding to these stimuli directly and indirectly.The process of mechanotransduction in osteocytes is a complex and finely tuned regulation involving interactions between the cell and its surrounding environment,neighboring cells,and various mechanosensors within the cells with distinct functions.The known major mechanosensors in osteocytes include primary cilia,Piezo ion channels,integrins,extracellular matrix,and connexin-based intercellular junctions.These mechanosensors play crucial roles in osteocytes,perceiving and transducing mechanical signals to regulate bone homeostasis.This review aims to provide a systematic introduction to these five mechanosensors,offering new perspectives and insights into understanding how osteocytes respond to mechanical stimuli and maintain bone tissue homeostasis.

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 safety of minimally invasive liver resection for resectable hepatocellular carcinoma (HCC) complicated with portal hypertension.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 807 patients with resectable HCC who underwent minimally invasive liver resection in 8 medical centers, including Sir Run Run Shaw Hospital, Affiliated with the Zhejiang University School of Medicine et al, from June 2011 to November 2022 were collected. There were 670 males and 137 females, aged 58(50,66)years. Of the 807 patients, 173 cases with portal hypertension were divided into the portal hypertension group, and 634 cases without portal hypertension were divided into the non-portal hypertension group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) intraoperative and post-operative situations; (3) subgroup analysis. Propensity score matching was done by the 1:1 nearest neighbor matching method, with the caliper setting as 0.001. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum 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 constructed using the non-parameter rank sun test. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of the 807 patients, 268 cases were successfully matched, including 134 cases in the portal hypertension group and 134 cases in the non-portal hypertension group. The elimination of the tumor diameter and robot-assisted surgery confounding bias ensured comparability between the two groups after propensity score matching. (2) Intraoperative and postoperative situations. The occlusion time of porta hepatis, cases with intraoperative blood transfusion, cases with postoperative complication, cases with complication >Ⅱ grade of Clavien-Dindo classification, cases of Clavien-Dindo classification as Ⅰ grade, Ⅱ grade, Ⅲ grade, Ⅳ grade, cases with liver related complication were 27.0(15.0,43.0)minutes, 33, 55, 15, 13, 29, 14, 1, 37 in the portal hypertension group, versus 35.0(22.0,60.0)minutes, 17, 25, 5, 14, 9, 4, 1, 13 in the non-portal hypertension group, showing significant differences in the above indicators between the two groups ( Z=-2.15, χ2=6.30, 16.39, 4.38, 20.72, 14.16, P<0.05). (3) Subgroup analysis. Results of subgroups analysis showed that in cases with major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 243.5(174.6,296.3)minutes, 200.0(150.0,600.0)mL, 7.5(6.0,13.0)days in the portal hypertension group, versus 270.0(180.0,314.5)minutes, 200.0 (75.0,450.0)mL, 7.0(5.5,10.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-0.54, -1.73, -0.92, P>0.05). In cases with non-major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 8.0(5.0,10.0)days in the portal hypertension group, versus 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.5,9.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-1.39, -0.10, 1.05, P>0.05). In cases with anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 210.0(150.0,285.0)minutes, 150.0(50.0,200.0)mL, 8.0(6.0,9.3)days in the portal hypertension group, versus 225.5(146.3,306.8)minutes, 100.0(50.0,250.0)mL, 7.0(6.0,9.0)days in the non-portal hypertension group, showing no significant difference in the above indica-tors between the two groups ( Z=-0.75, -0.26, -0.91, P>0.05). In cases with non-anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 173.5(120.0,231.5)minutes, 175.0(50.0,300.0)mL, 7.0(5.0,11.0)days in the portal hyper-tension group, versus 186.0(123.0,262.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.0,9.5)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-0.97, -1.12, -0.98, P>0.05). Conclusion:Minimally invasive liver resection or even major liver resection is safe and feasible for screened HCC patients complicated with portal hyper-tension, but attention should be paid to the prevention and treatment of postoperative complications.

Objective To characterize the distribution and assess the exposure to phthalic acid esters （PAEs） in the indoor dust of Shanghai City. Methods Samples were collected from 33 sampling sites， including homes， hotels， offices and public places， in Shanghai in 2018， 2019， and 2020. The samples were pretreated by 100 sieves， extracted and concentrated， and then analyzed by gas chromatography-mass spectrometry in selected ion mode （SIM）. Results Results on the characteristics of PAEs in indoor dust in different places showed that concentrations of PAEs were in a range of <0.01-2 464 mg·kg^-1.The average concentration of 16 PAEs was 613 mg·kg^-1. Bis（2-ethylhexyl） phthalate （DEHP）， di-iso-butyl phthalate （DiBP）， di-n-butyl phthalate （DBP） and di-n-octyl phthalate （DnOP） were the main components of PAEs in indoor dust， accounting for approximately 99.5% of 16 PAEs. The intake of DEHP， DBP， DEP and BBP was lower than the tolerable daily intake （TDI） and reference doses （RfD） set by EU CSTEE and U.S. EPA. Conclusion Average daily dose （ADD） via indoor dust is estimated， and the order of intake through different pathways is hand-oral intake>skin contact>respiratory inhalation. Exposure risk of PAEs in children is greater than that in adults.