Reciprocal regulation of T follicular helper cells and dendritic cells drives colitis development.

The immunological mechanisms underlying chronic colitis are poorly understood. T follicular helper (TFH) cells are critical in helping B cells during germinal center reactions. In a T cell transfer colitis model, a lymphoid structure composed of mature dendritic cells (DCs) and TFH cells was found within T cell zones of colonic lymphoid follicles. TFH cells were required for mature DC accumulation, the formation of DC-T cell clusters and colitis development. Moreover, DCs promoted TFH cell differentiation, contributing to colitis development. A lineage-tracing analysis showed that, following migration to the lamina propria, TFH cells transdifferentiated into long-lived pathogenic TH1 cells, promoting colitis development. Our findings have therefore demonstrated the reciprocal regulation of TFH cells and DCs in colonic lymphoid follicles, which is critical in chronic colitis pathogenesis.

DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25.

Neutrophil extracellular traps (NETs), which consist of chromatin DNA filaments coated with granule proteins, are released by neutrophils to trap microorganisms1-3. Recent studies have suggested that the DNA component of NETs (NET-DNA) is associated with cancer metastasis in mouse models4-6. However, the functional role and clinical importance of NET-DNA in metastasis in patients with cancer remain unclear. Here we show that NETs are abundant in the liver metastases of patients with breast and colon cancers, and that serum NETs can predict the occurrence of liver metastases in patients with early-stage breast cancer. NET-DNA acts as a chemotactic factor to attract cancer cells, rather than merely acting as a 'trap' for them; in several mouse models, NETs in the liver or lungs were found to attract cancer cells to form distant metastases. We identify the transmembrane protein CCDC25 as a NET-DNA receptor on cancer cells that senses extracellular DNA and subsequently activates the ILK-ß-parvin pathway to enhance cell motility. NET-mediated metastasis is abrogated in CCDC25-knockout cells. Clinically, we show that the expression of CCDC25 on primary cancer cells is closely associated with a poor prognosis for patients. Overall, we describe a transmembrane DNA receptor that mediates NET-dependent metastasis, and suggest that targeting CCDC25 could be an appealing therapeutic strategy for the prevention of cancer metastasis.

Early midcell localization of Escherichia coli PBP4 supports the function of peptidoglycan amidases.

Insertion of new material into the Escherichia coli peptidoglycan (PG) sacculus between the cytoplasmic membrane and the outer membrane requires a well-organized balance between synthetic and hydrolytic activities to maintain cell shape and avoid lysis. Since most bacteria carry multiple enzymes carrying the same type of PG hydrolytic activity, we know little about the specific function of given enzymes. Here we show that the DD-carboxy/endopeptidase PBP4 localizes in a PBP1A/LpoA and FtsEX dependent fashion at midcell during septal PG synthesis. Midcell localization of PBP4 requires its non-catalytic domain 3 of unknown function, but not the activity of PBP4 or FtsE. Microscale thermophoresis with isolated proteins shows that PBP4 interacts with NlpI and the FtsEX-interacting protein EnvC, an activator of amidases AmiA and AmiB, which are needed to generate denuded glycan strands to recruit the initiator of septal PG synthesis, FtsN. The domain 3 of PBP4 is needed for the interaction with NlpI and EnvC, but not PBP1A or LpoA. In vivo crosslinking experiments confirm the interaction of PBP4 with PBP1A and LpoA. We propose that the interaction of PBP4 with EnvC, whilst not absolutely necessary for mid-cell recruitment of either protein, coordinates the activities of PBP4 and the amidases, which affects the formation of denuded glycan strands that attract FtsN. Consistent with this model, we found that the divisome assembly at midcell was premature in cells lacking PBP4, illustrating how the complexity of interactions affect the timing of cell division initiation.

Quercetin: a promising virulence inhibitor of Pseudomonas aeruginosa LasB in vitro.

With the inappropriate use of antibiotics, antibiotic resistance has emerged as a major dilemma for patients infected with Pseudomonas aeruginosa. Elastase B (LasB), a crucial extracellular virulence factor secreted by P. aeruginosa, has been identified as a key target for antivirulence therapy. Quercetin, a natural flavonoid, exhibits promising potential as an antivirulence agent. We aim to evaluate the impact of quercetin on P. aeruginosa LasB and elucidate the underlying mechanism. Molecular docking and molecular dynamics simulation revealed a rather favorable intermolecular interaction between quercetin and LasB. At the sub-MICs of ≤256 µg/ml, quercetin was found to effectively inhibit the production and activity of LasB elastase, as well as downregulate the transcription level of the lasB gene in both PAO1 and clinical strains of P. aeruginosa. Through correlation analysis, significant positive correlations were shown between the virulence gene lasB and the QS system regulatory genes lasI, lasR, rhlI, and rhlR in clinical strains of P. aeruginosa. Then, we found the lasB gene expression and LasB activity were significantly deficient in PAO1 ΔlasI and ΔlasIΔrhlI mutants. In addition, quercetin significantly downregulated the expression levels of regulated genes lasI, lasR, rhlI, rhlR, pqsA, and pqsR as well as effectively attenuated the synthesis of signaling molecules 3-oxo-C12-HSL and C4-HSL in the QS system of PAO1. Quercetin was also able to compete with the natural ligands OdDHL, BHL, and PQS for binding to the receptor proteins LasR, RhlR, and PqsR, respectively, resulting in the formation of more stabilized complexes. Taken together, quercetin exhibits enormous potential in combating LasB production and activity by disrupting the QS system of P. aeruginosa in vitro, thereby offering an alternative approach for the antivirulence therapy of P. aeruginosa infections. KEY POINTS: • Quercetin diminished the content and activity of LasB elastase of P. aeruginosa. • Quercetin inhibited the QS system activity of P. aeruginosa. • Quercetin acted on LasB based on the QS system.

Multidimensional influencing factors of postpartum depression based on the perspective of the entire reproductive cycle: evidence from western province of China.

OBJECTIVE: China has a serious burden of Postpartum depression (PPD). In order to improve the current situation of high burden of PPD, this study explores the factors affecting PPD from the multidimensional perspectives with physiology, family support and social support covering the full-time chain of pre-pregnancy-pregnancy-postpartum. METHODS: A follow-up survey was conducted in the Qujing First People's Hospital of Yunnan Province from 2020 to 2022, and a total of 4838 pregnant women who underwent antenatal checkups in the hospital were enrolled as study subjects. Mothers were assessed for PPD using the Edinburgh Postnatal Depression Scale (EPDS), and logistic regression was used to analyse the level of mothers' postnatal depression and identify vulnerability characteristics. RESULTS: The prevalence of mothers' PPD was 46.05%, with a higher prevalence among those who had poor pre-pregnancy health, had sleep problems during pregnancy, and only had a single female fetus. In the family support dimension, only family care (OR = 0.52, 95% CI 0.42-0.64) and only other people care(OR = 0.78, 95% CI 0.64-0.96) were the protective factors of PPD. The experience risk of PPD was higher among mothers who did not work or use internet. CONCLUSION: The PPD level in Yunnan Province was significantly higher than the global and Chinese average levels. Factors affecting mothers' PPD exist in all time stages throughout pregnancy, and the influence of family support and social support on PPD shouldn't be ignored. There is an urgent need to extend the time chain of PPD, move its prevention and treatment forward and broaden the dimensions of its intervention.

Effect of piperine on the inhibitory potential of MexAB-OprM efflux pump and imipenem resistance in carbapenem-resistant Pseudomonas aeruginosa.

The escalating prevalence of carbapenem-resistant Pseudomonas aeruginosa (CRPA) poses a significant threat to global public health through the spread of its 'high-risk' clones. Immediate and decisive research into antimicrobial agents against CRPA is crucial for the development of effective measures and interventions. Overexpression of the MexAB-OprM efflux pump is one of the major mechanisms of CRPA. Since the active efflux of antibacterial agents plays a significant role in mediating drug resistance in CRPA, the inhibition of efflux pumps has become a promising strategy to restore antibacterial potency. Piperine (PIP) has been proven to be a promising efflux pump inhibitor in some bacteria. However, there are no studies on whether PIP can act as a potential efflux pump inhibitor in CRPA. The present study aimed to identify the antibacterial activity of PIP against CRPA and to evaluate the effect on the MexAB-OprM efflux pump. Molecular docking was used to analyze the possible interaction of PIP with the proteins of the MexAB-OprM efflux pump in CRPA. The effect of PIP on the expression of the MexAB-OprM efflux pump was investigated by real-time quantitative PCR (qPCR) and ethidium bromide accumulation efflux assay. The effect of PIP on CRPA imipenem (IPM) resistance was investigated by the checkerboard dilution method. The results demonstrated that PIP exhibited the lowest binding affinity of -9.1 kcal towards efflux pump proteins. A synergistic effect between PIP and IPM on CRPA was observed. More importantly, PIP effectively hindered the efflux of ethidium bromide and IPM by up-regulating MexR gene expression while down-regulating MexA, MexB, and OprM gene expressions. In conclusion, PIP could enhance the antibacterial activity of IPM by inhibiting the MexAB-OprM efflux pump. Our work proved that PIP had the potential to be an efflux pump inhibitor of CRPA.

Spatial effects of public health laboratory emergency testing institutions under COVID-19 in China.

BACKGROUND: The transmission of 2019 novel coronavirus (COVID-19) has caused global panic in the past three years. Countries have learned an important lesson in the practice of responding to COVID-19 pandemic: timely and accurate diagnosis is critical. As an important technology of virus diagnosis, nucleic acid testing (NAT) is also widely used in the identification of other infectious diseases. However, geographic factors often constrain the provision of public health services such as NAT services, and the spatial nature of their resource allocation is a significant problem. METHODS: We used OLS, OLS-SAR, GWR, GWR-SAR, MGWR, and MGWR-SAR models to identify the determinants of spatial difference and spatial heterogeneity affecting NAT institutions in China. RESULTS: Firstly, we identify that the distribution of NAT institutions in China shows a clear spatial agglomeration, with an overall trend of increasing distribution from west to east. There is significant spatial heterogeneity in Chinese NAT institutions. Secondly, the MGWR-SAR model results show that city level, population density, number of tertiary hospitals and number of public health emergency outbreaks are important factors influencing the spatial heterogeneity of NAT institutions in China. CONCLUSIONS: Therefore, the government should allocate health resources rationally, optimise the spatial layout of testing facilities, and improve the ability to respond to public health emergencies. Meanwhile, third-party testing facilities need to focus on their role in the public health emergency response system as a market force to alleviate the inequitable allocation of health resources between regions. By taking these measures to prepare adequately for possible future public health emergencies.

Swertia L.: A comprehensive review of its genetic relationship, chemical compositions, pharmacological effects, toxicities, and applications.

Swertia L., as a commonly used ethnic medicine, is widely distributed in Sichuan, Yunnan, and Xizang in China. Moreover, the medicinal plants of Swertia L. have been widely used and constitute one of the most important sources of various traditional medicines in China due to their prominent activities. In this review, the information on the classification, distribution, genetic relationship, chemical composition, pharmacological effects, toxicities, and applications of the medicinal plants in Swertia L. was summarized based on the scientific literature. The results indicated that the medicinal plants of Swertia L. mainly contained chemical components including triterpenes, xanthones, and iridoids. These compounds exert pharmacological effects including ameliorating diseases related to the liver and gallbladder. They also exert antiviral and antibacterial effects and can alleviate the increase in blood glucose levels. Especially, prescriptions related to Swertia L. have been widely adopted in preclinical and clinical studies to protect against diseases affecting the liver and the gallbladder, including hepatitis, cirrhosis, and cholecystitis. In addition, it also discusses toxicity studies and future perspectives and provides a reference for their clinical development and utilization.

Biomechanical improvement of anterior talofibular ligament by augmentation repair of ligament advance reinforcement system: a cadaver study.

BACKGROUND: Ankle sprain are one of the most frequent sports injuries. Some individuals will develop chronic lateral ankle instability (CLAI) after ankle sprain and suffer from recurrent ankle sprain. Current surgical treatment of CAI with anterior talofibular ligament (ATFL) rupture fails to restore the stability of the native ATFL. Ligament Advance Reinforcement System (LARS) augmentation repair of ATFL was developed to improve its primary stability after repaired. METHODS: This study was performed to evaluate whether LARS augmentation repair of ATFL had similar stability as the modified Broström repair and the intact ATFL to maintain ankle construct stability. Standardized surgical techniques were performed on eighteen fresh frozen cadaver ankle specimens. The intact ATFL group has just undergone an ATFL exploratory surgery. The modified Broström procedure is based on anatomical repair of the ATFL with a 2.9 mm suture anchor, and the LARS procedure is an augmentation procedure of the ATFL using LARS ligaments based on the modified Broström procedure. A dynamic tensile test machine was used to assess load-to-failure testing in the three groups. The ultimate failure load and stiffness were calculated and reported from the load-displacement curve. A one-way analysis of variance was used to detect significant differences (p < 0.05) between the LARS augmentation repair, the modified Broström repair and the intact ATFL, followed by least significant difference (LSD) post-hoc tests. RESULTS: The LARS augmentation repair group showed an increased in ultimate failure to load and stiffness compared to the other two groups. There were no significant differences in ultimate failure to load and stiffness between the modified Broström and the intact ATFL, the LARS ligament for ATFL augmentation allows for improved primary stability after repair and reduced stress on the repaired ATFL, which facilitates healing of the remnant ligament. CONCLUSIONS: The LARS augmentation repair of ATFL represents a stable technique that may allow for the ankle stability to be restored in patients with CAI after surgery.

NlpI-Prc Proteolytic Complex Mediates Peptidoglycan Synthesis and Degradation via Regulation of Hydrolases and Synthases in Escherichia coli.

Balancing peptidoglycan (PG) synthesis and degradation with precision is essential for bacterial growth, yet our comprehension of this intricate process remains limited. The NlpI-Prc proteolytic complex plays a crucial but poorly understood role in the regulation of multiple enzymes involved in PG metabolism. In this paper, through fluorescent D-amino acid 7-hydroxycoumarincarbonylamino-D-alanine (HADA) labeling and immunolabeling assays, we have demonstrated that the NlpI-Prc complex regulates the activity of PG transpeptidases and subcellular localization of PBP3 under certain growth conditions. PBP7 (a PG hydrolase) and MltD (a lytic transglycosylase) were confirmed to be negatively regulated by the NlpI-Prc complex by an in vivo degradation assay. The endopeptidases, MepS, MepM, and MepH, have consistently been demonstrated as redundantly essential "space makers" for nascent PG insertion. However, we observed that the absence of NlpI-Prc complex can alleviate the lethality of the mepS mepM mepH mutant. A function of PG lytic transglycosylases MltA and MltD as "space makers" was proposed through multiple gene deletions. These findings unveil novel roles for NlpI-Prc in the regulation of both PG synthesis and degradation, shedding light on the previously undiscovered function of lytic transglycosylases as "space makers" in PG expansion.

Development of a Miniature Mass Spectrometry System for Point-of-Care Analysis of Lipid Isomers Based on Ozone-Induced Dissociation.

Disorder of lipid homeostasis is closely associated with a variety of diseases. Although mass spectrometry (MS) approaches have been well developed for the characterization of lipids, it still lacks an integrated and compact MS system that is capable of rapid and detailed lipid structural characterization and can be conveniently transferred into different laboratories. In this work, we describe a novel miniature MS system with the capability of both ozone-induced dissociation (OzID) and collision-induced dissociation (CID) for the assignment of sites of unsaturation and sn-positions in glycerolipids. A miniature ozone generator was developed, which can be operated at a relatively high pressure. By maintaining high-concentration ozone inside the linear ion trap, OzID efficiency was significantly improved for the identification of C═C locations in unsaturated lipids, with reaction times as short as 10 ms. Finally, the miniature OzID MS system was applied to the analysis of C═C locations and sn-positions of lipids from biological samples. Direct sampling and fast detection of changes in phospholipid isomers were demonstrated for the rapid discrimination of breast cancer tissue samples, showing the potential of the miniature OzID MS system for point-of-care analysis of lipid isomer biomarkers in complex samples.

Transmission in home environment associated with the second wave of COVID-19 pandemic in India.

India has suffered from the second wave of COVID-19 pandemic since March 2021. This wave of the outbreak has been more serious than the first wave pandemic in 2020, which suggests that some new transmission characteristics may exist. COVID-19 is transmitted through droplets, aerosols, and contact with infected surfaces. Air pollutants are also considered to be associated with COVID-19 transmission. However, the roles of indoor transmission in the COVID-19 pandemic and the effects of these factors in indoor environments are still poorly understood. Our study focused on reveal the role of indoor transmission in the second wave of COVID-19 pandemic in India. Our results indicated that human mobility in the home environment had the highest relative influence on COVID-19 daily growth rate in the country. The COVID-19 daily growth rate was significantly positively correlated with the residential percent rate in most state-level areas in India. A significant positive nonlinear relationship was found when the residential percent ratio ranged from 100 to 120%. Further, epidemic dynamics modelling indicated that a higher proportion of indoor transmission in the home environment was able to intensify the severity of the second wave of COVID-19 pandemic in India. Our findings suggested that more attention should be paid to the indoor transmission in home environment. The public health strategies to reduce indoor transmission such as ventilation and centralized isolation will be beneficial to the prevention and control of COVID-19.

Degree of protection provided by poverty alleviation policies for the middle-aged and older in China: evaluation of effectiveness of medical insurance system tools and vulnerable target recognition.

BACKGROUND: China's medical insurance schemes and poverty alleviation policy at this stage have achieved population-wide coverage and the system's universal function. At the late stage of the elimination of absolute poverty task, how to further exert the poverty alleviation function of the medical insurance schemes has become an important agenda for targeted poverty alleviation. To analyse the risk of catastrophic health expenditure (CHE) occurrence in middle-aged and older adults with vulnerability characteristics from the perspectives of social, regional, disease, health service utilization and medical insurance schemes. METHODS: We used data from the 2018 China Health and Retirement Longitudinal Study (CHARLS) database and came up with 9190 samples. The method for calculating the CHE was adopted from WHO. Logistic regression was used to determine the different characteristics of middle-aged and older adults with a high probability of incurring CHE. RESULTS: The overall regional poverty rate and incidence of CHE were similar in the east, central and west, but with significant differences among provinces. The population insured by the urban and rural integrated medical insurance (URRMI) had the highest incidence of CHE (21.17%) and health expenditure burden (22.77%) among the insured population. Integration of Medicare as a medical insurance scheme with broader benefit coverage did not have a significant effect on the incidence of CHE in middle-aged and older people with vulnerability characteristics. CONCLUSIONS: Based on the perspective of Medicare improvement, we conducted an in-depth exploration of the synergistic effect of medical insurance and the poverty alleviation system in reducing poverty, and we hope that through comprehensive strategic adjustments and multidimensional system cooperation, we can lift the vulnerable middle-aged and older adults out of poverty.

Calycosin represses AIM2 inflammasome-mediated inflammation and pyroptosis to attenuate monosodium urate-induced gouty arthritis through NF-κB and p62-Keap1 pathways.

Gouty arthritis is an inflammatory disease induced by monosodium urate (MSU), and is closely related to the activation of inflammasomes. Calycosin plays an anti-inflammatory role in arthritis. This study explored the mechanism of Calycosin in MSU-induced gouty arthritis. MSU-induced gouty arthritis mouse models with or without treatment of Calycosin were established, and physiological and pathological indicators were determined. Similarly, peripheral blood mononuclear cells (PBMCs) and THP-1 macrophages were used in vitro. Lactate dehydrogenase (LDH) was tested. The degree of centrifugal infiltration was detected by immunofluorescence. ELISA and quantitative reverse-transcription polymerase chain reaction were conducted to determine the levels of inflammatory factors. Immunohistochemistry, immunofluorescence, and flow cytometry were utilized to detect the content of caspase-1. Protein expressions of NF-κB-, p62-Keap1 pathway-, and pyroptosis-related factors were examined by western blot. In MSU-induced mouse models, calycosin increased mechanical hyperalgesia but decreased the swelling index of the mouse knee joint in a time-dependent manner. MSU treatment increased inflammatory cells and LysM-eGFP+ neutrophils recruitment in vivo, and promoted the LDH content in vitro, and meanwhile, calycosin reversed the aforementioned effects of MSU. In addition, calycosin repressed the release of inflammatory factors, promoted p62 level and diminished the levels of AIM2, caspase-1, ASC, IL-1ß, Keap1, Cleaved GSDMD, and Cleaved caspase-1 and phosphorylation of p65 and IκBα in MSU-induced mouse or cell models. Furthermore, AIM2 silencing also inhibited MSU-induced inflammation and pyroptosis. Collectively, calycosin may inhibit AIM2 inflammasomes-mediated inflammation and pyroptosis through NF-κB and p62-Keap1 pathways, ultimately playing a protective role in gouty arthritis.

Pyroptosis inhibition alleviates potassium oxonate- and monosodium urate-induced gouty arthritis in mice.

OBJECTIVES: Pyroptosis has been found implicated in several diseases, however, whether it was involved in gouty arthritis remained unclear. Our study was performed to uncover the role of pyroptosis in gouty arthritis based on a mice model. METHODS: Mouse gouty arthritis model was established by injections of potassium oxonate (PO), monosodium urate (MSU) and pyroptosis suppressor disulfiram. The diameter of the ankle joints was measured, and ankle joints morphology was observed with hematoxylin-eosin (H&E) staining. Uric acid, creatinine and blood urea nitrogen (BUN) concentrations were measured, while cytokines level and xanthine oxidase (XOD) activity were quantified. Relative pyroptosis markers expressions were determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed. RESULTS: In mouse model, PO and MSU injections cause damage to right ankle, increase the root thickness ratio and uric acid, creatinine and BUN levels in serum and decrease the uric acid and creatinine levels in urine. Also, under PO and MSU treatment, up-regulated XOD activity, inflammatory cytokines levels and pyroptosis markers expressions are observed. Negative regulation of mice injury by disulfiram treatment is also observed. CONCLUSION: Pyroptosis inhibition might alleviate PO- and MSU-induced gouty arthritis, providing possible therapeutic strategies for gouty arthritis.

Arthroscopic internal drainage of popliteal cysts with cyst wall resection in pediatric patients.

Objectives: To evaluate the efficacy of arthroscopic internal drainage (AID) and cyst wall resection (CWR) in children with popliteal cysts. Methods: This study included 16 pediatric patients with popliteal cysts and received arthroscopy using the double posteromedial (PM) portal system during June 2020 and June 2021 at The General Hospital of Northern Theater Command. Among these pediatric patients, 14 were males and two were females, with the mean age of nine years (range: 7-12 years). The left knee was affected in 12 cases, while the right knee was involved in the rest four cases. All patients underwent MR imaging before the procedure to assess whether there was intra-articular trauma and whether the popliteal cyst communicated with the knee-joint cavity. The MRI results showed that each patient had a simple popliteal cyst that involved a single knee joint without intra-articular trauma, which was classified as Grade-1 (n=3), Grade-2 (n =10) or Grade-3 (n =3) according to the Rauschning and Lindgren grading of knee joint symptoms. Arthroscopy was performed through anterolateral (AL) and PM portals to the knee joint for AID plus CWR, and the surgical outcomes were evaluated based on the Rauschning and Lindgren criteria. Results: No major vascular or nerve injury occurred during the operation. Postoperative complications such as wound infection and lower-extremity deep venous thrombosis were not recorded in these patients. Complications involving the saphenous nerve or the great saphenous vein or pseudocyst formation were not observed during the follow-up period. All patients completed the follow-up ranging from 3-12 months and were identified to have grade-0 (n=15) and grade-1 (n=1) popliteal cysts based on the Rauschning and Lindgren criteria, indicating significant improvement compared with the preoperative levels (all p<0.05). Moreover, no recurrence was recorded after operation. Conclusion: AID plus CWR is a minimally invasive and safe approach for pediatric patients with popliteal cysts to promote postoperative recovery and reduce the recurrence rate.

Application of exposure enhancement technique combined with femoral condyle pushing technique in repairing the posterior horn of the medial meniscus under knee arthroscopy.

Objectives: To investigate the clinical efficacy of exposure enhancement technique and femoral condyle pushing technique applying in the posterior horn of the medial meniscus of the knee. Methods: From January 2016 to June 2019, 52 patients with injury in the medial meniscus treated in our department were selected. The horizontal tear of the posterior horn of the medial meniscus was repaired by exposure enhancement technique and femoral condyle pushing technique using the meniscus suture system. Postoperatively, the efficacy was evaluated using the Lysholm scoring system. Results: These 52 patients were all followed up for 3~18 months, with an average of 12.5 ± 7.3 months. The pain and activity of all patients were significantly improved compared with those before surgery. Conclusion: Exposure enhancement technique and femoral condyle pushing technique in the repair of the posterior horn of the medial meniscus presents satisfactory efficacy. It can improve the pain and activity of the knee, and enhance the stability of residual meniscus. Therefore, it is worth promoting.

Handheld Mass Spectrometer with Intelligent Adaptability for On-Site and Point-of-Care Analysis.

The development of miniature mass spectrometry (MS) systems with simple analysis procedures is important for the transition of applying MS analysis outside traditional analytical laboratories. Here, we present Mini 14, a handheld MS instrument with disposable sample cartridges designed based on the ambient ionization concept for intrasurgical tissue analysis and surface analysis. The instrumentation architecture consists of a single-stage vacuum chamber with a discontinuous atmospheric interface and a linear ion trap. A major effort in this study for technical advancement is on making handheld MS systems capable of automatically adapting to complex conditions for in-field analysis. Machine learning is used to establish the model for autocorrecting the mass offsets in the mass scale due to temperature variations and a new strategy is developed to extend the dynamic concentration range for analysis. Mini 14 weighs 12 kg and can operate on battery power for more than 3 h. The mass range exceeds m/z 2000, and the full peak width at half-maximum is Δm/z 0.4 at a scanning speed of 700 Th/s. The direct analysis of human brain tissue for identifying glioma associated with isocitrate dehydrogenase mutations has been achieved and a limit of detection of 5 ng/mL has been obtained for analyzing illicit drugs in blood.

miR-378-3p alleviates contusion spinal cord injury by negatively regulating ATG12.

MicroRNAs (miRNAs or miRs) serve essential roles in the pathogenic process of spinal cord injury (SCI). The present study investigated the role of miR-378-3p and autophagy-related 12 (ATG12) in SCI. RT-qPCR was used to detect the mRNA expression levels of miR-378-3p and ATG12. Cell viability and membrane integrity were evaluated using CCK-8 and LDH assays. For the analysis of the interaction between miR-378-3p and ATG12, a dual-luciferase reporter assay was conducted. The hindlimb function of rats was detected with the Basso, Beattie and Bresnahan score, and the motor deficit index score was used to evaluate nerve function. Using these approaches, it was identified that miR-378-3p expression was downregulated, while that of ATG12 was upregulated in SCI tissues and in cells exposed to hypoxia. Hypoxia repressed the expression of miR-378-3p via hypoxia-inducible factor 1-α. The overexpression of miR-378-3p exerted anti-apoptotic effects on nerve cells by directly repressing ATG12. The infusion of miR-378-3p improved hindlimb motor function and the neurological functions of rats with contusion SCI, which contributed to amelioration of functional deficits and the relief of contusion SCI. Therefore, it was concluded that upregulated expression of miR-378-3p in PC12 or N2A cells repressed the apoptosis of nerve cells, and the administration of miR-378-3p in model rats with contusion SCI improved neurological and motor functions.

Effects of sulfur application on selenium uptake and seed selenium speciation in soybean (Glycine max L.) grown in different soil types.

AIMS: The objective of the present study was to elucidate the effects of sulfur (S) application on selenium (Se) uptake and seed Se speciation in high-protein soybean (Glycine max L.) grown in different soil types. METHODS: Pot experiments were conducted with soybean plants grown in yellow-brown soil (pH 5.68) and in calcareous alluvial soil (pH 7.87). Sodium selenate (Na2SeO4, 2 mg kg-1) was applied to soil with or without S fertilizer (S, 100 mg kg-1). RESULTS: Soybean grain yield and total biomass in calcareous alluvial soil were both approximately 1.3-fold the levels in yellow-brown soil. Following Se application, seed Se concentration in calcareous alluvial soil was 3.2-fold the concentration in yellow-brown soil, although additional S application reduced the corresponding seed Se concentrations by 55.6% and 38.6%, respectively. Generally, Se application facilitated Se translocation and enrichment in soybean seeds. Organic Se accounted for 92% of seed total Se and Se-methionine (>90%) was always the major Se species. Available Se (soluble and exchangeable fractions) accounted for 50.7% (yellow-brown soil) and 70.1% (calcareous alluvial soil) of soil total Se under Se treatment, while additional S application decreased the corresponding proportion of soluble Se by 12.6% and 14.4%. CONCLUSIONS: The bioavailability of selenate in calcareous alluvial soil was higher than the bioavailability in yellow-brown soil and was more negatively affected by S application. Although S application inhibited Se uptake in soybean plants in both soil types, it did not influence seed Se speciation and Se-methionine was the major Se species.