Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Acute kidney injury (AKI) is a common clinically critical syndrome in hospitalized patients with high morbidity and mortality. At present, the mechanism of AKI has not been fully elucidated, and no therapeutic drugs exist. As known, glycolytic product lactate is a key metabolite in physiological and pathological processes. The kidney is an important gluconeogenic organ, where lactate is the primary substrate of renal gluconeogenesis in physiological conditions. During AKI, altered glycolysis and gluconeogenesis in kidneys significantly disturb the lactate metabolic balance, which exert impacts on the severity and prognosis of AKI. Additionally, lactate-derived posttranslational modification, namely lactylation, is novel to AKI as it could regulate gene transcription of metabolic enzymes involved in glycolysis or Warburg effect. Protein lactylation widely exists in human tissues and may severely affect non-histone functions. Moreover, the strategies of intervening lactate metabolic pathways are expected to bring a new dawn for the treatment of AKI. This review focused on renal lactate metabolism, especially in proximal renal tubules after AKI, and updated recent advances of lactylation modification, which may help to explore potential therapeutic targets against AKI.
Humans ; Acute Kidney Injury/metabolism* ; Lactic Acid/metabolism* ; Animals ; Glycolysis/physiology* ; Gluconeogenesis/physiology* ; Kidney/metabolism*

To achieve rapid and visual detection of Plasmodium vivax,a detection method based on recombinase polymerase amplification(RPA)technology and lateral flow dipstick(LFD)was established and evaluated.Targeting the conserved sequence of the P.vivax 18S rRNA gene(GenBank:DQ660817.1)as the target sequence,primers and probes were designed with Primer Premier 5,and the P.vivax recombinant plasmid(pUCPv)was constructed as the standard.A sensitive and specific RPA-LFD-based rapid visual detection method for P.vivax nucleic acids was established.The plasmid standard was serially diluted 10-fold to concentrations of 1×103,1×102,1×101,1×10?,and 1×10?1 copies/μL for sensitivity testing.To evaluate specificity,whole blood DNA samples from patients infected with Plasmodium falciparum,Plasmodium malariae,Plasmodium ovale,or Leishmania donovani,as well as healthy participants,were tested by RPA-LFD.Additionally,The assay′s accuracy was evaluated by testing whole blood DNA samples from 24 confirmed P.vivax-infected patients.This study successfully established a sensitive,specific,and rapid visual RPA-LFD method for detecting P.vivax nucleic acids.The assay can complete P.vivax detection within 20 minutes under isothermal conditions at 39 ℃,achieving a sensitivity of 1 copy/μL.There is no significant cross reaction with parasites such as other Plasmodium species and L.donovani,and the specificity is 100%.All 24 DNA samples from confirmed P.vivax patients were detected,showing a 100%detection rate.The developed RPA-LFD assay exhibits excellent sensitivity and specificity,requires only simple heating equipment,and is user-friendly.This rapid visual detection method is particularly suitable for P.vivax screening in low-resource settings.

Objective To determine the effect of knee extension constraint training on bilateral knee biomechanics and bilateral symmetry in running after anterior cruciate ligament reconstruction(ACLR).Methods A total of 33 male patients with unilateral ACL injuries were randomly assigned to a BRACE group of 14 wearing a brace with limitation of knee extension,a PLACEBO group of 10 wear-ing a brace without limitation of knee extension,and a CONTROL group of 9,wearing no brace.All groups underwent unilateral hamstring-auto graft ACLR surgery,immediately followed by 12-week rou-tine rehabilitation.Between week 13 and 48,both the BRACE and PLACEBO groups wore braces for one hour on Mondays.Then,running biomechanical tests were performed at the ends of Week 12 and Week 48,and the bilateral knee extension/flexion angle,moment and inter-leg difference(ILD)were calculated.One-dimensional statistical parametric mapping(SPM1d)two-way ANOVA with repeated measures on one factor was used to identify differences in bilateral knee biomechanics and ILD among the three groups before and after the intervention.Results There was no significant interaction effect of group and time on bilateral knee flexion angle,knee extension moment,and ILD in running(P>0.05).Moreover,no significant effect of group was found on the bilateral knee biomechanics and ILD in running(P>0.05).Additionally,significant effects of time were observed on bilateral knee flexion angle and extension moment in running.However,bilateral knee flexion angle decreased during termi-nal stance(ACLR leg:89%～100%,P=0.036;non-ACLR leg:94%～100%,P=0.046),while the bi-lateral knee extension moment increased during mid-stance(ACLR leg:17%～59%,P<0.001;non-ACLR leg:38%～61%,P<0.001)between week 12 and 48.Conclusion In this study,no improvement was found in the abnormal knee biomechanics and symmetry during running in male patients after uni-lateral ACL reconstruction through long-term knee extension constraint training.Moreover,within one year after ACL reconstruction,the knee extension moment of the surgical limb increased gradually over time,with no changes in the knee flexion angle of the surgical limb and bilateral knee symme-try,suggesting that abnormal knee biomechanics and bilateral symmetry should be paid attention to in the post-surgery rehabilitation.

Objective To determine the effect of knee extension constraint training on bilateral knee biomechanics and bilateral symmetry in running after anterior cruciate ligament reconstruction(ACLR).Methods A total of 33 male patients with unilateral ACL injuries were randomly assigned to a BRACE group of 14 wearing a brace with limitation of knee extension,a PLACEBO group of 10 wear-ing a brace without limitation of knee extension,and a CONTROL group of 9,wearing no brace.All groups underwent unilateral hamstring-auto graft ACLR surgery,immediately followed by 12-week rou-tine rehabilitation.Between week 13 and 48,both the BRACE and PLACEBO groups wore braces for one hour on Mondays.Then,running biomechanical tests were performed at the ends of Week 12 and Week 48,and the bilateral knee extension/flexion angle,moment and inter-leg difference(ILD)were calculated.One-dimensional statistical parametric mapping(SPM1d)two-way ANOVA with repeated measures on one factor was used to identify differences in bilateral knee biomechanics and ILD among the three groups before and after the intervention.Results There was no significant interaction effect of group and time on bilateral knee flexion angle,knee extension moment,and ILD in running(P>0.05).Moreover,no significant effect of group was found on the bilateral knee biomechanics and ILD in running(P>0.05).Additionally,significant effects of time were observed on bilateral knee flexion angle and extension moment in running.However,bilateral knee flexion angle decreased during termi-nal stance(ACLR leg:89%～100%,P=0.036;non-ACLR leg:94%～100%,P=0.046),while the bi-lateral knee extension moment increased during mid-stance(ACLR leg:17%～59%,P<0.001;non-ACLR leg:38%～61%,P<0.001)between week 12 and 48.Conclusion In this study,no improvement was found in the abnormal knee biomechanics and symmetry during running in male patients after uni-lateral ACL reconstruction through long-term knee extension constraint training.Moreover,within one year after ACL reconstruction,the knee extension moment of the surgical limb increased gradually over time,with no changes in the knee flexion angle of the surgical limb and bilateral knee symme-try,suggesting that abnormal knee biomechanics and bilateral symmetry should be paid attention to in the post-surgery rehabilitation.

To achieve rapid and visual detection of Plasmodium vivax,a detection method based on recombinase polymerase amplification(RPA)technology and lateral flow dipstick(LFD)was established and evaluated.Targeting the conserved sequence of the P.vivax 18S rRNA gene(GenBank:DQ660817.1)as the target sequence,primers and probes were designed with Primer Premier 5,and the P.vivax recombinant plasmid(pUCPv)was constructed as the standard.A sensitive and specific RPA-LFD-based rapid visual detection method for P.vivax nucleic acids was established.The plasmid standard was serially diluted 10-fold to concentrations of 1×103,1×102,1×101,1×10?,and 1×10?1 copies/μL for sensitivity testing.To evaluate specificity,whole blood DNA samples from patients infected with Plasmodium falciparum,Plasmodium malariae,Plasmodium ovale,or Leishmania donovani,as well as healthy participants,were tested by RPA-LFD.Additionally,The assay′s accuracy was evaluated by testing whole blood DNA samples from 24 confirmed P.vivax-infected patients.This study successfully established a sensitive,specific,and rapid visual RPA-LFD method for detecting P.vivax nucleic acids.The assay can complete P.vivax detection within 20 minutes under isothermal conditions at 39 ℃,achieving a sensitivity of 1 copy/μL.There is no significant cross reaction with parasites such as other Plasmodium species and L.donovani,and the specificity is 100%.All 24 DNA samples from confirmed P.vivax patients were detected,showing a 100%detection rate.The developed RPA-LFD assay exhibits excellent sensitivity and specificity,requires only simple heating equipment,and is user-friendly.This rapid visual detection method is particularly suitable for P.vivax screening in low-resource settings.

Objective To explore the health-related quality of life(HRQOL)among patients with multidrug-resistant and rifampin-resistant pulmonary tuberculosis(MDR/RR-PTB)and analyze its influencing factors.Methods Data was collected from 50 MDR/RR-PTB patients registered for treatment management in the"Tuberculosis Management Information System"in Bazhong City from 2021 to 2024 as resistance group.Fifty pulmonary tuberculosis patients sensitive to anti-tuberculosis drug treatment registered in the system during the same period were selected as control group.A cross-sectional survey method was employed using the quality of life instruments for chronic disease pulmonary tuberculosis(QLICD-PT)to measure and compare the HRQOL between two groups.Multiple linear regression analysis was used to analyze factors affecting the HRQOL of MDR/RR-PTB patients.Results Except for physiological function,there were statistically significant difference between MDR/RR-PTB group and control group in terms of total quality of life score,psychological function,social function,and specific modules(P＜0.05).Univariate analysis showed that there were statistically significant differences in the total quality of life scores among patients with different genders,medical insurance statuses,monthly family income situations,presence or absence of comorbidities,lymphocyte count,albumin,C-reactive protein,and body mass index(P＜0.05).Multiple linear regression analysis revealed that(P＜0.05)there was significant difference for the partial regression coefficient tests of patient's medical insurance and monthly family income situations(P＜0.05).Conclusion The HRQOL of MDR/RR-PTB patients is lower than that of pulmonary tuberculosis patients sensitive to anti-tuberculosis drugs.The patient's health insurance and monthly family income are potential factors affecting the HRQOL of MDR/RR-PTB patients.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

Objective To explore the feasibility of minimally invasive autopsy by natural orifice transluminal endoscopic surgery.Methods Autopsy was performed on a deceased patient with COVID-19 via transesophageal,transtrachea,and transgastric natural orifice transluminal endoscopic surgery.The white light endoscopic manifestations of the corresponding organs were observed,and organ tissue specimens were obtained for routine pathological examination.Results All four pathways reached the corresponding organs successfully.Diffuse congestion and submucous bleeding were seen in the trachea,bronchus and bronchus of the pulmonary lobes.The bronchus of the left lower lobe was filled with dark red sputum;the surface of the left lung was congested obviously.Four thrombi and plaque rupture were seen on the aortic wall.The gastric mucosa was congested,eroded,and had active ulcers.The surface of heart and liver was smooth.Small lamellar panniculitis was seen in the omentum.Routine pathology showed chronic inflammation with acute inflammation of the bronchial mucosa and inflammatory exudation,and partial squamous metaplasia of the epithelium.In lung tissue,some alveolar epithelial hyperplasia,a little fibrin-like exudation,widened alveolar septa,and infiltration of acute and chronic inflammatory cells were seen.The columnar epithelial mucosa of the gastric mucosa showed chronic inflammation with acute inflammation and exudates and fungal masses.Conclusion Natural orifice transluminal endoscopic surgery is feasible for autopsy,and covid-19 virus can cause multi-system and multi-organ damage.

Intramedullary needle(IMN)has the advantages of high healing rate and low incidence of complications in treatment of tibial fracture,and has become one of the most commonly used fixation methods for the treatment of tibial fracture.However,due to the patient's own factors,fracture location and fracture type,infection and surgical treatment,bone nonunion after IMN still occurs in clinic.Bone nonunion leads to the increase of medical cost and prolonged the hospitalization time of patients,which causes great pain to patients,and also brings great challenges to the treatment of orthopedic surgeons.Therefore,this paper reviews the influencing factors of bone nonunion after IMN for tibial fracture,in order to provide reference for clinical treatment.