PD-L1 regulates tumor proliferation and T-cell function in NF2-associated meningiomas.

INTRODUCTION: Programmed death-ligand 1 (PD-L1) expression is an immune evasion mechanism that has been demonstrated in many tumors and is commonly associated with a poor prognosis. Over the years, anti-PD-L1 agents have gained attention as novel anticancer therapeutics that induce durable tumor regression in numerous malignancies. They may be a new treatment choice for neurofibromatosis type 2 (NF2) patients. AIMS: The aims of this study were to detect the expression of PD-L1 in NF2-associated meningiomas, explore the effect of PD-L1 downregulation on tumor cell characteristics and T-cell functions, and investigate the possible pathways that regulate PD-L1 expression to further dissect the possible mechanism of immune suppression in NF2 tumors and to provide new treatment options for NF2 patients. RESULTS: PD-L1 is heterogeneously expressed in NF2-associated meningiomas. After PD-L1 knockdown in NF2-associated meningioma cells, tumor cell proliferation was significantly inhibited, and the apoptosis rate was elevated. When T cells were cocultured with siPD-L1-transfected NF2-associated meningioma cells, the expression of CD69 on both CD4+ and CD8+ T cells was partly reversed, and the capacity of CD8+ T cells to kill siPD-L1-transfected tumor cells was partly restored. Results also showed that the PI3K-AKT-mTOR pathway regulates PD-L1 expression, and the mTOR inhibitor rapamycin rapidly and persistently suppresses PD-L1 expression. In vivo experimental results suggested that anti-PD-L1 antibody may have a synergetic effect with the mTOR inhibitor in reducing tumor cell proliferation and that reduced PD-L1 expression could contribute to antitumor efficacy. CONCLUSIONS: Targeting PD-L1 could be helpful for restoring the function of tumor-infiltrating lymphocytes and inducing apoptosis to inhibit tumor proliferation in NF2-associated meningiomas. Dissecting the mechanisms of the PD-L1-driven tumorigenesis of NF2-associated meningioma will help to improve our understanding of the mechanisms underlying tumor progression and could facilitate further refinement of current therapies to improve the treatment of NF2 patients.

Diagnostic efficiency of conventional ultrasound, shear wave elastography, and superb microvascular imaging in evaluating ulnar neuropathy at the elbow.

INTRODUCTION/AIMS: The current diagnosis of ulnar neuropathy at the elbow (UNE) relies mainly on the clinical presentation and nerve electrodiagnostic (EDX) testing, which can be uncomfortable and yield false negatives. The aim of this study was to investigate the diagnostic value of conventional ultrasound, shear wave elastography (SWE), and superb microvascular imaging (SMI) in diagnosing UNE. METHODS: We enrolled 40 patients (48 elbows) with UNE and 48 healthy volunteers (48 elbows). The patients were categorized as having mild, moderate or severe UNE based on the findings of EDX testing. The cross-sectional area (CSA) was measured using conventional ultrasound. Ulnar nerve (UN) shear wave velocity (SWV) and SMI were performed in a longitudinal plane. RESULTS: Based on the EDX findings, UNE severity was graded as mild in 4, moderate in 10, and severe in 34. The patient group showed increased ulnar nerve CSA and stiffness at the site of maximal enlargement (CSA mean at the site of max enlargement [CSAmax] and SWV mean at the site of max enlargement [SWVmax]), ulnar nerve CSA ratio, and stiffness ratio (elbow-to-upper arm), compared with the control group (p < .001). Furthermore, the severe UNE group showed higher ulnar nerve CSAmax and SWVmax compared with the mild and moderate UNE groups (p < .001). The cutoff values for diagnosis of UNE were 9.5 mm2 for CSAmax, 3.06 m/s for SWVmax, 2.00 for CSA ratio, 1.36 for stiffness ratio, and grade 1 for SMI. DISCUSSION: Our findings suggest that SWE and SMI are valuable diagnostic tools for the diagnosis and assessment of severity of UNE.

Dynamic Microcirculation Characteristics of Plantar Skin Under Metatarsal Head of Human Foot in Response to Life-Like Pressure Stimulus.

OBJECTIVE: Diabetic foot ulcer (DFU) is a severe complication with high mortality. High plantar pressure and poor microcirculation are considered main causes of DFU. The specific aims were to provide a novel technique for real-time measurement of plantar skin blood flow (SBF) under walking-like pressure stimulus and delineate the first plantar metatarsal head dynamic microcirculation characteristics because of life-like loading conditions in healthy individuals. METHODS: Twenty young healthy participants (14 male and 6 female) were recruited. The baseline (i.e., unloaded) SBF of soft tissue under the first metatarsal head were measured using laser Doppler flowmetry (LDF). A custom-made machine was utilized to replicate daily walking pressure exertion for 5 min. The exerted plantar force was adjusted from 10 N (127.3 kPa) to 40 N (509.3 kPa) at an increase of 5 N (63.7 kPa). Real-time SBF was acquired using the LDF. After each pressure exertion, postload SBF was measured for comparative purposes. Statistical analysis was performed using the R software. RESULTS: All levels of immediate-load and postload SBF increased significantly compared with baseline values. As the exerted load increased, the postload and immediate-load SBF tended to increase until the exerted load reached 35 N (445.6 kPa). However, in immediate-load data, the increasing trend tended to level off as the exerted pressure increased from 15 N (191.0 kPa) to 25 N (318.3 kPa). For postload and immediate-load SBF, they both peaked at 35 N (445.6 kPa). However, when the exerted force exceeds 35 N (445.6 kPa), both the immediate-load and postload SBF values started to decrease. CONCLUSIONS: Our study offered a novel real-time plantar soft tissue microcirculation measurement technique under dynamic conditions. For the first metatarsal head of healthy people, 20 N (254.6 kPa)-plantar pressure has a fair microcirculation stimulus compared with higher pressure. There might be a pressure threshold at 35 N (445.6 kPa) for the first metatarsal head, and soft tissue microcirculation may decrease when local pressure exceeds it.

Use of Mobile Technologies to Streamline Pretriage Patient Flow in the Emergency Department: Observational Usability Study.

BACKGROUND: In emergency departments (EDs), triage nurses are under tremendous daily pressure to rapidly assess the acuity level of patients and log the collected information into computers. With self-service technologies, patients could complete data entry on their own, allowing nurses to focus on higher-order tasks. Kiosks are a popular working example of such self-service technologies; however, placing a sufficient number of unwieldy and fixed machines demands a spatial change in the greeting area and affects pretriage flow. Mobile technologies could offer a solution to these issues. OBJECTIVE: The aim of this study was to investigate the use of mobile technologies to improve pretriage flow in EDs. METHODS: The proposed stack of mobile technologies includes patient-carried smartphones and QR technology. The web address of the self-registration app is encoded into a QR code, which was posted directly outside the walk-in entrance to be seen by every ambulatory arrival. Registration is initiated immediately after patients or their proxies scan the code using their smartphones. Patients could complete data entry at any site on the way to the triage area. Upon completion, the result is saved locally on smartphones. At the triage area, the result is automatically decoded by a portable code reader and then loaded into the triage computer. This system was implemented in three busy metropolitan EDs in Shanghai, China. Both kiosks and smartphones were evaluated randomly while being used to direct pretriage patient flow. Data were collected during a 20-day period in each center. Timeliness and usability of medical students simulating ED arrivals were assessed with the After-Scenario Questionnaire. Usability was assessed by triage nurses with the Net Promoter Score (NPS). Observations made during system implementation were subject to qualitative thematic analysis. RESULTS: Overall, 5928 of 8575 patients performed self-registration on kiosks, and 7330 of 8532 patients checked in on their smartphones. Referring effort was significantly reduced (43.7% vs 8.8%; P<.001) and mean pretriage waiting times were significantly reduced (4.4, SD 1.7 vs 2.9, SD 1.0 minutes; P<.001) with the use of smartphones compared to kiosks. There was a significant difference in mean usability scores for "ease of task completion" (4.4, SD 1.5 vs 6.7, SD 0.7; P<.001), "satisfaction with completion time" (4.5, SD 1.4 vs 6.8, SD 0.6; P<.001), and "satisfaction with support" (4.9, SD 1.9 vs 6.6, SD 1.2; P<.001). Triage nurses provided a higher NPS after implementation of mobile self-registration compared to the use of kiosks (13.3% vs 93.3%; P<.001). A modified queueing model was identified and qualitative findings were grouped by sequential steps. CONCLUSIONS: This study suggests patient-carried smartphones as a useful tool for ED self-registration. With increased usability and a tailored queueing model, the proposed system is expected to minimize pretriage waiting for patients in the ED.

Medial-pivot total knee arthroplasty enhances tibiofemoral axial rotation stability in weight-bearing mid-range flexion compared to posterior-stabilised system.

PURPOSE: Total knee arthroplasty (TKA) stands as a primary intervention for severe knee ailments, yet concerns remain regarding postoperative patient satisfaction and flexion instability. This study aims to evaluate the in-vivo kinematics of medial-pivot (MP) and posterior-stabilised (PS) designs during step-up activity, in comparison to the kinematics of the nonoperated contralateral knee. METHODS: Sixteen patients with PS-TKA and 14 with MP-TKA were retrospectively examined. Clinical outcomes were assessed using patient-completed questionnaires. Motion during step-up was captured using a dual fluoroscopic system. Statistical analysis was applied to evaluate the in-vivo tibiofemoral six-degree-of-freedom kinematics and articular contact positions between the two groups. RESULTS: Despite being older, patients in the MP group reported higher postoperative subjective scores for weight-bearing functional activities. The axial rotation centres of MP-TKA located on the medial tibial plateau exhibited less variance compared to PS-TKA and contralateral knees. Compared to the contralateral knee (contralateral to medial-pivot [C-MP] or contralateral to posterior-stabilised [C-PS]), the MP group exhibited limited range of motion in terms of anteroposterior translation (MP: 3.6 ± 1.3 mm vs. C-MP: 7.4 ± 2.5 mm, p < 0.01) and axial rotation (MP: 6.6 ± 1.9° vs. C-MP: 10.3 ± 4.9°, p = 0.02), as well as in the PS group for anteroposterior translation (PS: 3.9 ± 1.7 mm vs. C-PS: 7.2 ± 3.7 mm, p < 0.01). CONCLUSION: The MP group with better postoperative ratings demonstrated a more stable MP axial rotation pattern during step-up activity compared to the PS group, underscoring the pivotal role of prosthetic design in optimising postoperative rehabilitation and functional recovery. LEVEL OF EVIDENCE: Level III.

Strictosamide promotes wound healing through activation of the PI3K/AKT pathway.

Nauclea officinalis, as a Chinese medicine in Hainan province, had the effect of treating lower limb ulcers, burn infections. In this paper, we studied the effect of Strictosamide (STR), the main bioactive compound in Nauclea officinals, on wound healing and explored its internal mechanism. Firstly, the wound healing potential of STR was evaluated in a rat model, demonstrating its ability to expedite wound healing, mitigate inflammatory infiltration, and enhance collagen deposition. Additionally, immunofluorescence analysis revealed that STR up-regulated the expression of CD31 and PCNA. Subsequently, target prediction, protein-protein interaction (PPI), gene ontology (GO), and pathway enrichment analyses were used to obtain potential targets, specific biological processes, and molecular mechanisms of STR for the potential treatment of wound healing. Furthermore, molecular docking was conducted to predict the binding affinity between STR and its associated targets. Additionally, in vivo and in vitro experiments confirmed that STR could increase the expression of P-PI3K, P-AKT and P-mTOR by activating the PI3K/AKT signaling pathway. In summary, this study provided a new explanation for the mechanism by which STR promotes wound healing through network pharmacology, suggesting that STR may be a new candidate for treating wound.

Use of a pH-responsive imatinib mesylate sustained-release hydrogel for the treatment of tendon adhesion by inhibiting PDGFRß/CLDN1 pathway.

Adhesion after tendon injury, which can result in limb movement disorders, is a common clinical complication; however, effective treatment methods are lacking. Hyaluronic acid hydrogels are a new biomedical material used to prevent tendon adhesion owing to their good biocompatibility. In addition, potential drugs that inhibit adhesion formation have gradually been discovered. The anti-adhesion effects of a combination of loaded drugs into hydrogels have become an emerging trend. However, current drug delivery systems usually lack specific regulation of drug release, and the effectiveness of drugs for treating tendon adhesions is mostly flawed. In this study, we identified a new drug, imatinib mesylate (IM), that prevents tendon adhesion and explored its related molecular pathways. In addition, we designed a pH-responsive sustained-release hydrogel for delivery. Using the metal-organic framework ZIF-8 as a drug carrier, we achieved controlled drug release to increase the effective drug dose at the peak of adhesion formation to achieve better therapeutic effects. The results showed that IM blocked the formation of peritendon adhesions by inhibiting the PDGFRß/ERK/STAT3/CLDN1 pathway. Furthermore, the hydrogel with ZIF-8 exhibited better physical properties and drug release curves than the hydrogel loaded only with drugs, showing better prevention and treatment effects on tendon adhesion.

A unit process log reduction database for water reuse practitioners.

Pathogen reduction for the purpose of human health protection is a critical function provided by water reuse systems. Pathogen reduction performance potential is dependent on a wide range of design and operational parameters. Poor understanding of pathogen reduction performance has important consequences-under treatment can jeopardize human health, while over treatment can lead to unnecessary costs and environmental impacts. Documented pathogen reduction potential of the unit processes that make up water reuse treatment trains is based on a highly dispersed and unstructured literature, creating an impediment to practitioners looking to design, model or simply better understand these systems. This review presents a database of compiled log reduction values (LRVs) and log reduction credits (LRCs) for unit processes capable of providing some level of pathogen reduction, with a focus on processes suitable for onsite non-potable water reuse systems. Where reported, we have also compiled all relevant design and operational factors associated with the LRVs and LRCs. Overall, we compiled over 1100 individual LRV data entries for 31 unit processes, and LRCs for 8 unit processes. Results show very inconsistent reporting of influencing parameters, representing a limitation to the use of some of the data. As a standalone resource, the database (included as Supplemental Information) provides water reuse practitioners with easy access to LRV and LRC data. The database is also part of a longer-term effort to optimize the balance between human health protection, potential environmental impacts and cost of water reuse treatment trains.

Innovation and entrepreneurship of Chinese returning migrant workers in their home region.

This study aims to investigate the influence of pre-entrepreneurial career mobility frequency and job changes among returning migrant workers (RMWs) on the innovation level of enterprises, with a particular focus on the mediating role of urban social capital accumulated by RMWs. Using data from the "current entrepreneurial status of RMWs", we applied an ordered probit model to validate our hypotheses. To address endogeneity, a recursive bivariate probit model was used, and stepwise regression combined with bootstrap methods was employed to ascertain the mediating influence of urban social capital. Our results demonstrate a significant positive correlation (P < 0.01) between pre-entrepreneurial career mobility frequency and the innovation level of enterprises among RMWs. However, there's a notable negative correlation (P < 0.01) between experiences as elementary workers and enterprise innovation level, while technical and marketing roles correlate positively (P < 0.01) with enterprise innovation level. Urban social capital mediates the relationship between career mobility and enterprise innovation level, suggesting that career mobility enhance urban social capital accumulation, influencing RMWs' enterprise innovation levels. This empirical evidence holds even after robustness tests. We further observed that RMWs with fewer than three career moves lean towards low level of enterprise innovation, while those with three or more gravitate towards high level of enterprise innovation. This study advances the theory of career mobility and enriches the understanding of enterprise innovation levels. Additionally, it provides critical theoretical insights for prospective RMWs entrepreneurs in strategizing their career mobility and job changes. Policy implications suggest that, in addition to providing entrepreneurial support, the government should facilitate pre-entrepreneurial career mobility channels for migrant workers and consider the transition from rural to urban employment as a socialized ritual for RMWs engaging in entrepreneurship.

Suitability of the MP1000 Platform for Robot-assisted Prostatectomy: A Prospective Randomised Controlled Trial.

Background and objective: Robot-assisted radical prostatectomy (RARP) is widely used because of the many advantages of a robotic approach. The da Vinci Si robot is one of the most commonly used surgical robot systems, but it may be associated with higher costs owing to the use of consumable surgical supplies. Our aim was to conduct a preliminary investigation of the capability of the MP1000 system for RARP. Methods: In this prospective, multicentre, single-blinded study, we randomly assigned 42 patients scheduled to undergo RARP between April and September 2021 to a da Vinci Si group (control) or an MP1000 group (intervention). Patients underwent RARP performed using the assigned robotic system and were followed up at 3-mo intervals. The primary outcome was the rate of conversion to open/laparoscopic surgery. Secondary outcomes were installation and operation times, intraoperative blood loss, postoperative surgical margin status, hospital stay, incontinence, complications, safety indicators, and surgeon ergonomics. Key findings and limitations: All procedures were successfully completed without conversion to open/laparascopic surgery or major complications. Secondary outcomes, including oncological and ergonomic indicators, did not differ significantly between the groups over the study period. One patient in the control group experienced dysuria (Clavien-Dindo grade 3). No patients had incontinence at 3 mo. A limitation of the study is the small sample size. Conclusions and clinical implications: RARP with the MP1000 system is feasible, safe, and effective in the management of localised prostate cancer. Patient summary: We assessed the effectiveness and safety of the new MP1000 robot system for robot-assisted removal of the prostate in comparison to the da Vinci Si robot. We found no difference in effectiveness or safety among 42 patients with prostate cancer who were assigned randomly to one of the two systems. We conclude that the MP1000 is a suitable robot for this surgery.

Molecular Mechanism of Yangshen Maidong Decoction in the Treatment of Chronic Heart Failure based on Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulations.

Chronic heart failure (CHF) is a complex multifactorial clinical syndrome leading to abnormal cardiac structure and function. The severe form of this ailment is characterized by high disability, high mortality, and morbidity. Worldwide, 2-17% of patients die at first admission, of which 17-45% die within 1 year of admission and >50% within 5 years. Yangshen Maidong Decoction (YSMDD) is frequently used to treat the deficiency and pain of the heart. The specific mechanism of action of YSMDD in treating CHF, however, remains unclear. Therefore, a network pharmacology-based strategy combined with molecular docking and molecular dynamics simulations was employed to investigate the potential molecular mechanism of YSMDD against CHF. The effective components and their targets of YSMDD and related targets of CHF were predicted and screened based on the public database. The network pharmacology was used to explore the potential targets and possible pathways that involved in YSMDD treated CHF. Molecular docking and molecular dynamics simulations were performed to elucidate the binding affinity between the YSMDD and CHF targets. Screen results, 10 main active ingredients, and 6 key targets were acquired through network pharmacology analysis. Pathway enrichment analysis showed that intersectional targets associated pathways were enriched in the Prostate cancer pathway, Hepatitis B pathway, and C-type lectin receptor signaling pathways. Molecular docking and molecular dynamics simulations analysis suggested 5 critical active ingredients have high binding affinity to the 5 key targets. This research shows the multiple active components and molecular mechanisms of YSMDD in the treatment of CHF and offers resources and suggestions for future studies.

[Determination of 12 prohibited veterinary drug residues in pig urine by ultra high performance liquid chromatography-tandem mass spectrometry].

A method was established for the simultaneous detection of 12 prohibited veterinary drugs, including ß2-receptor agonists, nitrofuran metabolites, nitroimidazoles, chlorpromazine, and chloramphenicol, in pig urine. The sample was pretreated by enzymolysis, acid hydrolysis/derivatization, and liquid-liquid extraction combined with solid-phase extraction. Detection was performed using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Ammonium acetate solution (0.2 mol/L, 4.5 mL) and ß-glucuronidase/aryl sulfatase (40 µL) were added to the sample, which was subsequently enzymolized at 37 ℃ for 2 h. Then, 1.5 mL of 1.0 mol/L hydrochloric acid solution and 100 µL of 0.1 mol/L o-nitrobenzaldehyde solution were added to the sample. The mixture was incubated at 37 ℃ for 16 h, and the analytes were extracted with 8 mL of ethyl acetate by liquid-liquid extraction. The lower aqueous phase obtained after extraction was extracted and purified using a mixed cation-exchange solid-phase extraction column. The extracts were combined, the extraction solution was blow-dried with nitrogen, and the residue was redissolved for determination. The samples were analyzed under multiple-reaction monitoring mode with both positive and negative electrospray ionization, and quantified using an isotope internal standard method. The correlation coefficients (r) of the 12 compounds were >0.99. The limits of detection (LODs) and quantification (LOQs) of chloramphenicol were 0.05 and 0.1 µg/L, respectively, and the LODs and LOQs of the other compounds were 0.25 and 0.5 µg/L, respectively. The mean recoveries and RSDs at 1, 2, and 10 times the LOQ were 83.6%-115.3% and 2.20%-12.34%, respectively. The proposed method has the advantages of high sensitivity, good stability, and accurate quantification; thus, it is suitable for the simultaneous determination of the 12 prohibited veterinary drug residues in pig urine.

Uptake of gadolinium and dexamethasone in rat inner ear and facial nerve using different administrations.

BACKGROUND: The pathway by which drugs are injected subcutaneously behind the ear to act on the inner ear has not been fully elucidated. OBJECTIVES: To compare the uptake of gadopentetate dimeglumine (Gd-DTPA) and dexamethasone (Dex) in the cochlea and facial nerve of rats following different administrations. MATERIALS AND METHODS: Magnetic resonance imaging was applied to observe the distribution of Gd-DTPA in the facial nerve and inner ear. We observed the uptake of Dex after it was injected with different methods. RESULTS: Images of the intravenous (IV) and intramuscular (IM) groups showed that the bilateral cochlea of the rat was visualized almost simultaneously. While in the left post-auricular (PA) injection group, it was asynchronous. The maximum accumulation (Cmax) of the Gd in the left facial nerve of the PA group (35.406 ± 5.32) was substantially higher than that of the IV group (16.765 ± 3.7542) (p < .01). CONCLUSIONS: Compared with systemic administration, PA has the advantages of long Gd and Dex action time and high accumulation concentration to treat facial nerve diseases. SIGNIFICANCE: The distribution of Gd and Dex in the inner ear and facial nerve of rats following PA injection might be unique.

Associations between Total Atherosclerosis Burden of Baroreceptor-Resident Arteries and ECG Abnormalities after Acute Ischemic Stroke.

Electrocardiogram (ECG) abnormalities are the most common cardiac complications after acute ischemic stroke (AIS) and predict poor outcomes. The arterial baroreflex is an essential determinant of cardiovascular autonomic regulation, with receptors mainly residing in carotid sinuses and aortic arch. The atherosclerosis of these baroreceptor-resident arteries (BRA) is very common in AIS patients and might impair baroreflex function. However, the associations between the atherosclerosis of BRA and ECG abnormalities after AIS are still unknown. In total, 228 AIS patients within 7 days after onset without a pre-existing heart disease were prospectively recruited. With computed tomography angiography, atherosclerosis conditions in 10 segments of the carotid sinuses and aortic arch were scored and summed as the Total Atherosclerosis Burden of BRA (TAB-BRA), and asymptomatic coronary artery stenosis (ACAS) ≥50% was simultaneously assessed. We performed 12-lead ECG to dynamically detect abnormal repolarization, and 24 h Holter ECG to monitor arrhythmias and heart rate variability (HRV) parameters, which are reliable indicators to assess cardiac autonomic function. We found that TAB-BRA was positively associated with abnormal repolarization (OR 1.09; CI% 1.03-1.16; p = 0.003) and serious cardiac arrhythmias (OR 1.08; CI% 1.01-1.15; p = 0.021). In addition, TAB-BRA was an important predictor of abnormal repolarization, persisting over 3 days (OR 1.17; CI% 1.05-1.30; p = 0.003). However, ACAS ≥ 50% did not relate to these ECG abnormalities. TAB-BRA was negatively correlated with parasympathetic-related HRV parameters. Our results indicated that AIS patients with a high TAB-BRA are more likely to have ECG abnormalities and delayed normalization, which may relate to the decreased cardiac parasympathetic activity, but not the accompanied ACAS ≥ 50%.

China's "coal-to-gas" policy had large impact on PM1.0 distribution during 2016-2019.

Particulate matter with an aerodynamic diameter of less than 1 µm (PM1.0) can be extremely hazardous to human health, so it is imperative to accurately estimate the spatial and temporal distribution of PM1.0 and analyze the impact of related policies on it. In this study, a stacking generalization model was trained based on aerosol optical depth (AOD) data from satellite observations, combined with related data affecting aerosol concentration such as meteorological data and geographic data. Using this model, the PM1.0 concentration distribution in China during 2016-2019 was estimated, and verified by comparison with ground-based stations. The coefficient of determination (R2) of the model is 0.94, and the root-mean-square error (RMSE) is 8.49 µg/m3, mean absolute error (MAE) is 4.10 µg/m3, proving that the model has a very high performance. Based on the model, this study analyzed the PM1.0 concentration changes during the heating period (November and December) in the regions where the "coal-to-gas" policy was implemented in China, and found that the proposed "coal-to-gas" policy did reduce the PM1.0 concentration in the implemented regions. However, the lack of natural gas due to the unreasonable deployment of the policy in the early stage caused the increase of PM1.0 concentration. This study can provide a reference for the next step of urban air pollution policy development.

Optimal intersurface stability for unicompartmental femoral component design with two pegs placed on the distal resection surface: 5 mm peg length increment and 10° peg inclination.

PURPOSE: The present study aimed to identify the optimal design of the unicompartmental femoral component through parameter analysis and stability evaluation. METHODS: A finite element (FE) analysis was applied to analyse and adjust the parameter combinations of the anterior tilt angle of the posterior condyle resection surface, the position of the peg, the length of the peg and the inclination angle of the peg, resulting in 10 different FE models. Setting three knee flexion angles of 8.4° (maximum load state during walking), 40° (maximum load state during stair climbing) and 90° (maximum load state during squatting exercise), quantitatively analysing the micromotion values of the bone-prosthesis interface and defining a weighted scoring formula to evaluate the stability of different FE models. The validity of the FE analysis was verified using the Digital Image Correlation (DIC) device. RESULTS: The errors between the FE analysis and the DIC test at three flexion angles were 5.6%, 1.7% and 11.1%. The 10 different femoral component design models were measured separately. The FE analysis demonstrated that the design with a 0° anterior tilt angle of the posterior condyle resection surface, both pegs placed on the distal resection surface, lengthened 5 mm pegs and a 10° peg inclination angle provided the best stability. CONCLUSION: The current study proposed a method for evaluating the stability of the femoral component design. The optimal intersurface stability design of the unicompartmental femoral component was achieved with two pegs placed on the distal resection surface, a 5-mm peg length increment and a 10° peg inclination. These results might provide a reference for the selection of unicompartmental femoral components in clinical practice and therefore improve the survival rate of future unicompartmental knee arthroplasty. LEVEL OF EVIDENCE: Level III.

Endoplasmic Reticulum Dysfunction: An Emerging Mechanism of Vitiligo Pathogenesis.

The endoplasmic reticulum (ER) is the main site of protein synthesis, transport, and modification. Its abnormal status has now emerged as an established cause of many pathological processes, such as tumors and autoimmune diseases. Recent studies also demonstrated that the defective functions of ER may lead to pigmentary diseases. Vitiligo is a depigmenting ailment skin disorder whose pathogenesis is now found to be associated with ER. However, the detailed mechanism is still unclear. In this review, we try to link the association between ER with its inter- and intra-organellar interactions in vitiligo pathogenesis and focus on the function, mechanism, and clinical potential of ER with vitiligo. Expand ER is found in melanocytes of vitiligo and ER stress (ERS) might be a bridge between oxidative stress and innate and adaptive immunity. Meanwhile, the tight association between ER and mitochondria or melanosomes in organelles levels, as well as genes and cytokines, is the new paradigm in the pathogenesis of vitiligo. This undoubtedly adds a new aspect to the understanding of vitiligo, facilitating the design of targeted therapies for vitiligo.

CircPIAS1 promotes hepatocellular carcinoma progression by inhibiting ferroptosis via the miR-455-3p/NUPR1/FTH1 axis.

BACKGROUND: The role of circRNAs in hepatocellular carcinoma (HCC) progression remains unclear. CircPIAS1 (circBase ID: hsa_circ_0007088) was identified as overexpressed in HCC cases through bioinformatics analysis. This study aimed to investigate the oncogenic properties and mechanisms of circPIAS1 in HCC development. METHODS: Functional analyses were conducted to assess circPIAS1's impact on HCC cell proliferation, migration, and ferroptosis. Xenograft mouse models were employed to evaluate circPIAS1's effects on tumor growth and pulmonary metastasis in vivo. Bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays were utilized to elucidate the molecular pathways influenced by circPIAS1. Additional techniques, including RNA pulldown, fluorescence in situ hybridization (FISH), chromatin immunoprecipitation (ChIP), qPCR, and western blotting, were used to further explore the underlying mechanisms. RESULTS: CircPIAS1 expression was elevated in HCC tissues and cells. Silencing circPIAS1 suppressed HCC cell proliferation and migration both in vitro and in vivo. Mechanically, circPIAS1 overexpression inhibited ferroptosis by competitively binding to miR-455-3p, leading to upregulation of Nuclear Protein 1 (NUPR1). Furthermore, NUPR1 promoted FTH1 transcription, enhancing iron storage in HCC cells and conferring resistance to ferroptosis. Treatment with ZZW-115, an NUPR1 inhibitor, reversed the tumor-promoting effects of circPIAS1 and sensitized HCC cells to lenvatinib. CONCLUSION: This study highlights the critical role of circPIAS1 in HCC progression through modulation of ferroptosis. Targeting the circPIAS1/miR-455-3p/NUPR1/FTH1 regulatory axis may represent a promising therapeutic strategy for HCC.

Analysis of the synergistic benefits of typical technologies for pollution reduction and carbon reduction in the iron and steel industry in the Beijing-Tianjin-Hebei region.

With its high energy consumption and pollutant emissions, the iron and steel industry is a significant source of air pollution and carbon emissions in the Beijing-Tianjin-Hebei (BTH) region. To improve air quality and reduce greenhouse gas emissions, a series of policies involving ultra-low emission, synergistic reduction of pollution, and carbon application have been implemented in the region. This study has assessed air pollutant and CO2 emission patterns in the iron and steel industry of the region by employing co-control effects coordinate system, marginal abatement cost curve, and numerical modeling, along with the synergistic benefits of typical technologies. The results have demonstrated that: (1) the intensive production activities pertinent to iron and steel enterprises has contributed greatly to the emission in Tangshan and Handan, where the sintering process is the main source of SO2, NOx, PM2.5, and CO, accounting for 64.86%, 55.15%, 29.98%, and 46.43% of the total emissions, respectively. (2) Among the typical pollution control and reduction measures, industrial restructuring and adjustment of the energy-resource structure have led to the greatest effects on emission reduction. Technologies exhibiting great potential in emission reduction and high-cost efficiency such as Blast Furnace Top Gas Recovery Turbine Unit (TRT) need to be promoted. (3) In Tangshan city with the highest level of steel production, the iron and steel production activities contributed to the concentration of 30.51% of PM2.5, 50.67% of SO2, and 42.54% of NO2 during the non-heating period. During the heating period, pollutants pertinent to the combustion of fossil energy for heating have increased, while iron and steel induced emissions have decreased to 23.7%, 34.32%, and 29.13%, respectively. By 2030, it is speculated that the contribution of the iron and steel industry to air quality will be significantly decreased as result of successful implementation of ultra-low emission policies and typical synergistic reduction technologies.

Da-Chai-Hu-Tang Formula inhibits the progression and metastasis in HepG2 cells through modulation of the PI3K/AKT/STAT3-induced cell cycle arrest and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Da-Chai-Hu-Tang (DCHT), a Chinese traditional herbal compound, has been utilized for the treatment of Hepatic diseases in China for over 1800 years. The DCHT formula contains eight herbals: Bupleurum chinense DC. (chaihu), Scutellaria baicalensis Georgi (huangqin), Paeonia lactiflora Pall. (baishao), Pinellia ternata (Thunb.) Makino (banxia), Rheum officinale Baill. (dahuang), Citrus × aurantium L. (zhishi), Zingiber officinale Roscoe (shengjiang), Ziziphus jujuba Mill. (dazao). Clinical studies have demonstrated the effectiveness of DCHT in hepatocellular carcinoma (HCC) and its ability to enhance the immunity of patients with hepatocellular carcinoma. A total of 20 Chinese articles have been published on the use of DCHT in treating HCC. AIM OF THE STUDY: The study aimed to validate the effect of DCHT in HCC cells and to identify related targets (TP53, AKT1, BCL2, STAT3) in treating HCC by DCHT in vitro experiments. MATERIALS AND METHODS: Cell proliferation and migration were investigated in vitro. Flow cytometry analysis was used to evaluate the cell cycle and apoptosis. Apoptotic bodies in HepG2 cells were observed using a confocal microscope. Biochemical detection was employed to analyze LDH release, MDA levels, and SOD levels. Bioinformatics analysis was used to predict core targets between DCHT and HCC, as well as potential signaling pathways. The protein levels of metastasis-associated, apoptosis, and PI3K, AKT, p-AKT, and STAT3 were further determined through Western blotting. RESULTS: Following treatment with DCHT, the inhibition of viability, migration, and G2/M arrest was observed in HepG2 cells. Flow cytometry analysis and Morphological apoptosis studies provided evidence that DCHT could induce apoptosis in HepG2 cells. Biochemical detection revealed that DCHT could increase LDH release and the level of MDA, and inhibit the viability of the SOD. Bioinformatics analysis identified key targets such as TP53, AKT1, BCL2, STAT3. The PI3K/AKT/STAT3 signaling pathway emerged as a critical pathway in the KEGG enrichment analysis. Western blotting results indicated that DCHT could enhance the expression of E-cadherin, p53, and Bax, while reducing the content of N-cadherin, Bcl-2, PI3K, p-AKT, AKT1, and STAT3. CONCLUSIONS: The results proved that DCHT could inhibit the progression and metastasis of HCC by regulating the expression of E-cadherin, N-cadherin, p53, Bax, Bcl-2, PI3K, p-AKT, AKT, and STAT3 through the PI3K/AKT/STAT3 signaling pathway.