Buried interface molecular hybrid for inverted perovskite solar cells.

Perovskite solar cells (PSCs) with an "inverted" architecture are a key pathway for commercializing this emerging photovoltaic technology due to the better power conversion efficiency (PCE) and operational stability as compared to the "normal" device structure. Specifically, PCEs of the inverted PSCs have exceeded 25% owing to the development of improved self-assembled molecules (SAMs)1-5 and passivation strategies6-8. Nevertheless, poor wettability and agglomerations of SAMs9-12 will cause interfacial losses, impeding further improvement in PCE and stability. Herein, we report on molecular hybrid at the buried interface in inverted PSCs by co-assembling a multiple carboxylic acid functionalized aromatic compound of 4,4',4''-nitrilotribenzoicacid (NA) with a popular SAM of [4-(3,6-dime-thyl-9H-carbazol-9-yl)butyl]phosphonic acid (Me-4PACz) to improve the heterojunction interface. The molecular hybrid of Me-4PACz with NA could substantially improve the interfacial characteristics. The resulting inverted PSCs demonstrated a record-certified steady-state efficiency of 26.54%. Crucially, this strategy aligns seamlessly with large-scale manufacturing, achieving the highest certified PCE for inverted mini-modules at 22.74% (aperture area: 11.1 cm2). Our device also maintained 96.1% of its initial PCE after more than 2,400 hours of 1-sun operation in ambient air.

Modulating the Distribution of Formamidinium Iodide by Ultrahigh Humidity Treatment Strategy for High-Quality Sequential Vapor Deposited Perovskite.

The quality of two-step processed perovskites is significantly influenced by the distribution of organic amine salts. Especially, modulating the distribution of organic amine salts remains a grand challenge for sequential vapor-deposited perovskites due to the blocking effect of bottom compact PbI2. Herein, an ultrahigh humidity treatment strategy is developed to facilitate the diffusion of formamidinium iodide (FAI) from the top surface to the buried bottom interface on the sequential vapor-deposited bilayer structure. Both experimental and theoretical investigations elucidate the mechanism that moisture helps to i) create FAI diffusion channels by inducing a phase transition from α- to δ-phase in the perovskite, and ii) enhance the diffusivity of FAI by forming hydrogen bonds. This ultrahigh humidity treatment strategy enables the formation of a desired homogeneous and high-quality α-phase after annealing. As a result, a champion efficiency of 22.0% is achieved and 97.5% of its initial performance is maintained after aging for 1050 h under ambient air with a relative humidity of up to 80%. This FAI diffusion strategy provides new insights into the reproducible, scalable, and high-performance sequential vapor-deposited perovskite solar cells.

Lead Iodide Redistribution Enables In Situ Passivation for Blading Inverted Perovskite Solar Cells with 24.5% Efficiency.

Blade-coating stands out as an alternative for fabricating scalable perovskite solar cells. However, it demands special control of the precursor composition regarding nucleation and crystallization and currently exhibits lower performance than the spin-coating process. It is mainly the resulting film morphology and excess lead iodide (PbI2) distribution that influences the optoelectronic properties. Here, the effectiveness of introducing N-Methyl-2-pyrrolidone (NMP) to regulate the structure of the perovskite layer and the redistribution of PbI2 is found. The introduction of NMP leads to the accumulation of excess PbI2, mainly on the top surface, reducing residual PbI2 at the perovskite buried interface. This not only facilitates the passivation of perovskite grain boundaries but also eliminates the potential degradation of the PbI2 triggered by light illumination in the perovskite buried interface. The optimized NMP-modified inverted perovskite solar cell achieves a champion efficiency of 24.5%, among the highest reported blade-coated perovskite solar cells. Furthermore, 13.68 cm2 blading perovskite solar modules are fabricated and demonstrate an efficiency of up to 20.4%. These findings underscore that with proper modulation of precursor composition, blade-coating can be a feasible and superior alternative for manufacturing high-quality perovskite films, paving the way for their large-scale applications in photovoltaic technology.

Low-Temperature Chemical Bath Deposition of Conformal and Compact NiOX for Scalable and Efficient Perovskite Solar Modules.

A scalable and low-cost deposition of high-quality charge transport layers and photoactive perovskite layers are the grand challenges for large-area and efficient perovskite solar modules and tandem cells. An inverted structure with an inorganic hole transport layer is expected for long-term stability. Among various hole transport materials, nickel oxide has been investigated for highly efficient and stable perovskite solar cells. However, the reported deposition methods are either difficult for large-scale conformal deposition or require a high vacuum process. Chemical bath deposition is supposed to realize a uniform, conformal, and scalable coating by a solution process. However, the conventional chemical bath deposition requires a high annealing temperature of over 400 °C. In this work, an amino-alcohol ligand-based controllable release and deposition of NiOX using chemical bath deposition with a low calcining temperature of 270 °C is developed. The uniform and conformal in-situ growth precursive films can be adjusted by tuning the ligand structure. The inverted structured perovskite solar cells and large-area solar modules reached a champion PCE of 22.03% and 19.03%, respectively. This study paves an efficient, low-temperature, and scalable chemical bath deposition route for large-area NiOX thin films for the scalable fabrication of highly efficient perovskite solar modules.

Two-Second-Annealed 2D/3D Perovskite Films with Graded Energy Funnels and Toughened Heterointerfaces for Efficient and Durable Solar Cells.

The 2D/3D perovskite heterostructures have been widely investigated to enhance the efficiency and stability of perovskite solar cells (PSCs). However, rational manipulation of phase distribution and energy level alignment in such 2D/3D perovskite hybrids are still of great challenge. Herein, we successfully achieved spontaneous phase alignment of 2D/3D perovskite heterostructures by concurrently introducing both 2D perovskite component and organic halide additive. The graded phase distribution of 2D perovskites with different n values and 3D perovskites induced favorable energy band alignment across the perovskite film and boosted the charge transfer at the relevant heterointerfaces. Moreover, the 2D perovskite component also acted as a "band-aid" to simultaneously passivate the defects and release the residual tensile stress of perovskite films. Encouragingly, the blade-coated PSCs based on only ≈2 s in-situ fast annealed 2D/3D perovskite films with favorable energy funnels and toughened heterointerfaces achieved promising efficiencies of 22.5 %, accompanied by extended lifespan. To our knowledge, this is the highest reported efficiency for the PSCs fabricated with energy-saved thermal treatment just within a few seconds, which also outperformed those state-of-the-art annealing-free analogues. Such a two-second-in-situ-annealing technique could save the energy cost by up to 99.6 % during device fabrication, which will grant its low-coast implementation.

Long-stranded non-coding RNA HCG11 regulates glioma cell proliferation, apoptosis and drug resistance via the sponge MicroRNA-144COX-2 axis.

In the current study, we analyzed long non-coding RNA HCG11 regulates the proliferation, apoptosis and drug resistance of glioma cells by spongy microRNA-144COX-2 axis. For this purpose, glioma cells at the logarithmic growth stage were divided into blank, up-regulated and down-regulated groups. The blank group did not undergo any treatment. Bacteria were inserted into the complete culture medium of the up-regulated group and down-regulated group for co-culture for 24 h. The down-regulated group was transfected with Mir-HCG11 inhibitor. The expressions of Mir-HCG11, Mir-144-3p and COX-2 in each group were observed, and the proliferation and apoptosis of glioma cells were analyzed, and their drug resistance was analyzed. Results showed that compared with the blank group, the expression of Mir-HCG11 and Mir-144 was increased and the expression of COX-2 was decreased in the up-regulated group (P < 0.05). Compared with the up-regulated group, the down-regulated group increased the expression of Mir-HCG11 and Mir-144 and decreased the expression of COX-2 (P < 0.05). Compared with the blank group, the proliferation rate of glioma cells in the up-regulated group (24h, 48h, 72h) was increased (P < 0.05); Compared with the up-regulated group, the proliferation rate of glioma cells in the down-regulated group (24h, 48h, 72h) was decreased (P < 0.05); Compared with the blank group, apoptosis rate of glioma cells in the up-regulated group (24h, 48h, 72h) was decreased (P < 0.05); Compared with the up-regulated group, the apoptosis rate of glioma cells in the down-regulated group (24h, 48h, 72h) was increased (P < 0.05); The IC50 values of Imatinib, VP-16 and TMZ in blank group and up-regulated group was compared (P > 0.05). Compared with the blank group and up-regulated group, the IC50 values of Imatinib, VP-16 and TMZ in the down-regulated group were decreased (P < 0.05). In general, down-regulation of long non-coding RNA-HCG11 can regulate the microRNA-144COX-2 axis in glioma, thus reducing the proliferation rate of glioma cells and improving the apoptosis rate of glioma cells. In addition, down-regulation of long non-coding RNA-HCG11 is also involved in the drug resistance mechanism of Imatinib, VP-16 and TMZ chemotherapy drugs.

Comparison of outcome between percutaneous pedicle screw fixation and the Mini-Open Wiltse Approach with pedicle screw fixation for neurologically intact thoracolumbar fractures: A retrospective study.

BACKGROUND: The purpose of this study was to compare the outcome between percutaneous pedicle screw fixation (PPSF) and the mini-open Wiltse approach with pedicle screw fixation (MWPSF) for neurologically intact thoracolumbar fractures. METHODS: From January 2017 to January 2019, ninety-four patients with neurologically intact thoracolumbar fractures were included in this study. In this retrospective study, forty-nine patients were operated with the PPSF and forty-five patients received MWPSF. The clinical information, surgery-related results and radiographic outcome were collected and compared between the two groups. RESULTS: There was no significant difference between the two groups in total length of incisions, blood loss, post-operative hospitalization time, visual analog scale (VAS) score and Oswestry disability index (ODI) score. There was also no significant difference in the accuracy rate of pedicle screw placement between two groups; however, the facet joint violation (FJV) was significantly higher in the PPSF group. The atrophic area of multifidus muscle in the PPSF group is significantly larger than that in the MWPSF group and the operative time of MWPSF group was shorter than that in the PPSF group. Meanwhile, the PPSF group obtaining significantly more cumulative exposure to radiation (p < 0.001). The result of vertebral body angle (VBA), Cobb's angle and AVH rate in the MWPSF group were significantly better than those in the PPSF group at the last post-operative follow-up. CONCLUSIONS: Both minimally invasive treatment techniques (PPSF and MWPSF) are safe and effective in treatment of neurologically intact thoracolumbar fractures. Nevertheless, our results indicate that MWPSF may be a better choice for neurologically intact thoracolumbar fractures, since it protects multifidus muscle, and decreases facet joint violation, operation time, as well as radiation exposure. In addition, MWPSF was associated with better reduction of kyphosis.

Comparison of Variations Between Spectral Doppler and Gaussian Surface Integration Methods for Umbilical Vein Blood Volume Flow.

OBJECTIVES: We are studying a new method for estimating blood volume flow that uses 3-dimensional ultrasound to measure the total integrated flux through an ultrasound-generated Gaussian surface that intersects the umbilical cord. This method makes none of the assumptions typically required with standard 1-dimensional spectral Doppler volume flow estimates. We compared the variations in volume flow estimates between techniques in the umbilical vein. METHODS: The study was Institutional Review Board approved, and all 12 patients gave informed consent. Because we had no reference standard for the true umbilical vein volume flow, we compared the variations of the measurements for the flow measurement techniques. At least 3 separate spectral Doppler and 3 separate Gaussian surface measurements were made along the umbilical vein. Means, standard deviations, and coefficients of variation (standard deviation/mean) for the flow estimation techniques were calculated for each patient. P < .05 was considered significant. RESULTS: The ranges of the mean volume flow estimates were 174 to 577 mL/min for the spectral Doppler method and 100 to 341 mL/min for the Gaussian surface integration (GSI) method. The mean standard deviations (mean ± SD) were 161 ± 95 and 45 ± 48 mL/min for the spectral Doppler and GSI methods, respectively (P < .003). The mean coefficients of variation were 0.46 ± 0.17 and 0.18 ± 0.14 for the spectral Doppler and GSI methods respectively (P < 0.002). CONCLUSIONS: The new volume flow estimation method using 3-dimensional ultrasound appears to have significantly less variation in estimates than the standard 1-dimensional spectral Doppler method.

Dual-frequency piezoelectric transducers for contrast enhanced ultrasound imaging.

For many years, ultrasound has provided clinicians with an affordable and effective imaging tool for applications ranging from cardiology to obstetrics. Development of microbubble contrast agents over the past several decades has enabled ultrasound to distinguish between blood flow and surrounding tissue. Current clinical practices using microbubble contrast agents rely heavily on user training to evaluate degree of localized perfusion. Advances in separating the signals produced from contrast agents versus surrounding tissue backscatter provide unique opportunities for specialized sensors designed to image microbubbles with higher signal to noise and resolution than previously possible. In this review article, we describe the background principles and recent developments of ultrasound transducer technology for receiving signals produced by contrast agents while rejecting signals arising from soft tissue. This approach relies on transmitting at a low-frequency and receiving microbubble harmonic signals at frequencies many times higher than the transmitted frequency. Design and fabrication of dual-frequency transducers and the extension of recent developments in transducer technology for dual-frequency harmonic imaging are discussed.

The thickness change ratio and preservation ratio of the infrapatellar fat pad are related to anterior knee pain in patients following medial patellofemoral ligament reconstruction.

BACKGROUND: The infrapatellar fat pad (IPFP) lies extrasynovial and intracapsular, preserving the joint cavity and serving as a biochemical regulator of inflammatory reactions. However, there is a lack of research on the relationship between anterior knee pain (AKP) and the IPFP after medial patellofemoral ligament reconstruction (MPFLR). Pinpointing the source of pain enables clinicians to promptly manage and intervene, facilitating personalized rehabilitation and improving patient prognosis. METHODS: A total of 181 patients were included in the study. These patients were divided into the AKP group (n = 37) and the control group (n = 144). Clinical outcomes included three pain-related scores, Tegner activity score, patient satisfaction, etc. Imaging outcomes included the IPFP thickness, IPFP fibrosis, and the IPFP thickness change and preservation ratio. Multivariate analysis was used to determine the independent factors associated with AKP. Finally, the correlation between independent factors and three pain-related scores was analyzed to verify the results. RESULTS: The control group had better postoperative pain-related scores and Tegner activity score than the AKP group (P < 0.01). The AKP group had lower IPFP thickness change ratio and preservation ratio (P < 0.001), and smaller IPFP thickness (P < 0.05). The multivariate analysis revealed that the IPFP thickness change ratio [OR = 0.895, P < 0.001] and the IPFP preservation ratio [OR = 0.389, P < 0.001] were independent factors related to AKP, with a significant correlation between these factors and pain-related scores [|r| > 0.50, P < 0.01]. CONCLUSIONS: This study showed the lower IPFP change ratio and preservation ratio may be independent factors associated with AKP after MPFLR. Early detection and targeted intervention of the underlying pain sources can pave the way for tailored rehabilitation programs and improved surgical outcomes. LEVEL OF EVIDENCE LEVEL III.

Optimizing early neurological deterioration prediction in acute ischemic stroke patients following intravenous thrombolysis: a LASSO regression model approach.

Background: Acute ischemic stroke (AIS) remains a leading cause of disability and mortality globally among adults. Despite Intravenous Thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) emerging as the standard treatment for AIS, approximately 6-40% of patients undergoing IVT experience Early Neurological Deterioration (END), significantly impacting treatment efficacy and patient prognosis. Objective: This study aimed to develop and validate a predictive model for END in AIS patients post rt-PA administration using the Least Absolute Shrinkage and Selection Operator (LASSO) regression approach. Methods: In this retrospective cohort study, data from 531 AIS patients treated with intravenous alteplase across two hospitals were analyzed. LASSO regression was employed to identify significant predictors of END, leading to the construction of a multivariate predictive model. Results: Six key predictors significantly associated with END were identified through LASSO regression analysis: previous stroke history, Body Mass Index (BMI), age, Onset to Treatment Time (OTT), lymphocyte count, and glucose levels. A predictive nomogram incorporating these factors was developed, effectively estimating the probability of END post-IVT. The model demonstrated robust predictive performance, with an Area Under the Curve (AUC) of 0.867 in the training set and 0.880 in the validation set. Conclusion: The LASSO regression-based predictive model accurately identifies critical risk factors leading to END in AIS patients following IVT. This model facilitates timely identification of high-risk patients by clinicians, enabling more personalized treatment strategies and optimizing patient management and outcomes.

Treatment of Pauwels III femoral neck fracture in young patients using biplane double support screw internal fixation technology based on X-ray image.

Traditional treatment methods have certain limitations. In recent years, the technique of internal fixation with double-plane double-supported screws based on X-ray images has been proposed to improve the therapeutic effect. The main objective of this research was to examine the effectiveness of the X-ray image-based bi-planar double-braced screw internal fixation technique . During surgery, the procedure was determined based on X-ray images, followed by an open reduction procedure at the fracture site, and finally internal fixation using bi-planar double-support screws. All patients were successfully treated with X-ray image-based bi-planar double support screw fixation. After surgery, X-ray images showed a good reduction of the fracture site without significant loosening or failure of the internal fixation. At the postoperative follow-up, the patient's pain symptoms were significantly relieved, and no significant complications occurred during recovery.

Unraveling the Predictors of Enlarged Perivascular Spaces: A Comprehensive Logistic Regression Approach in Cerebral Small Vessel Disease.

Background: This study addresses the predictive modeling of Enlarged Perivascular Spaces (EPVS) in neuroradiology and neurology, focusing on their impact on Cerebral Small Vessel Disease (CSVD) and neurodegenerative disorders. Methods: A retrospective analysis was conducted on 587 neurology inpatients, utilizing LASSO regression for variable selection and logistic regression for model development. The study included comprehensive demographic, medical history, and laboratory data analyses. Results: The model identified key predictors of EPVS, including Age, Hypertension, Stroke, Lipoprotein a, Platelet Large Cell Ratio, Uric Acid, and Albumin to Globulin Ratio. The predictive nomogram demonstrated strong efficacy in EPVS risk assessment, validated through ROC curve analysis, calibration plots, and Decision Curve Analysis. Conclusion: The study presents a novel, robust EPVS predictive model, providing deeper insights into EPVS mechanisms and risk factors. It underscores the potential for early diagnosis and improved management strategies in neuro-radiology and neurology, highlighting the need for future research in diverse populations and longitudinal settings.

Higher cardiovascular disease risks in people living with HIV: A systematic review and meta-analysis.

Background: The prognosis of AIDS after active antiretroviral therapy (ART) and the quality of life of people living with HIV (PLWH) are both affected by non-AIDS-related diseases such as cardiovascular disease (CVD). However, the specific risk ratios between PLWH and individuals negative for HIV are poorly understood. We aimed to systematically review and investigate the CVD risk factors associated with HIV. Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library databases between 1 January 2015, and 12 May 2023 for articles reported the prevalence and risk factors of CVD such as hypertension, dyslipidaemia, coronary artery disease (CAD), and myocardial infarction (MI). Due to the high heterogeneity, we used a random-effects model to analyse the data. All statistical analyses were performed using Stata/MP 17.0 with 95% confidence intervals (CIs). Results: We analysed 31 eligible studies including 312 913 PLWH. People living with HIV had higher risks of dyslipidaemia (hazard ratio (HR) = 1.53; 95% CI = 1.29, 1.82), CAD (HR = 1.37; 95% CI = 1.24, 1.51), and MI (HR = 1.47; 95% CI = 1.28, 1.68) compared to individuals without HIV. However, there were no significant differences in the prevalence of hypertension between groups (HR = 1.17; 95% CI = 0.97, 1.41). Subgroup analysis revealed that men with HIV, PLWH who smoked and the elderly PLWH had a high prevalence of CVD. Moreover, the disease prevalence patterns varied among regions. In the USA and Europe, for instance, some HRs for CVD were higher than in other regions. Active ART initiation after 2015 appears to have a lower risk of CVD (hypertension, hyperlipidaemia, CAD). All outcomes under analysis showed significant heterogeneity (I2>70%, P < 0.001), which the available study-level variables could only partially account for. Conclusions: People living with HIV had a higher CVD risk than the general population; thus, CVD prevention in PLWH requires further attention. Rapid initiation of ART may reduce the incidence of CVD in PLWH. For timely screening of CVD high-risk individuals and thorough disease management to prevent CVD, further studies are required to evaluate the risk factors for CVD among PLWH, such as age, region, etc. Registration: PROSPERO (CRD42021255508).

Hidden blood loss between percutaneous pedicle screw fixation and the mini-open Wiltse approach with pedicle screw fixation for neurologically intact thoracolumbar fractures: a retrospective study.

BACKGROUND: The aim of this study was to determine the proportion of hidden blood loss (HBL) in patients treated with minimally invasive surgery, and to compare the HBL between patients treated with percutaneous pedicle screw fixation (PPSF) and the mini-open Wiltse approach with pedicle screw fixation (MWPSF). METHODS: From January 2017 to January 2019, a total of 119 patients with thoracolumbar fractures were included in the analysis, of which 58 cases received PPSF and 61 cases received MWPSF. The clinical information and demographic results were collected and compared. And the HBL of the patients is calculated by the combination formulas of Nadler, Gross and Sehat. RESULTS: Compared with the PPSF group, operation time of MWPSF is shorter. The fluoroscopy times are 13.6 ± 3.0 in PPSF group and 5.6 ± 1.6 in MWPSF group (p < 0.001). As shown in Table 3, the intraoperative blood loss in PPSF group is 31.9 ± 9.6 ml, which is significantly less than that in the MWPSF group (44.0 ± 14.9 ml). The HBL (445.7 ± 228.9 ml), and HBL% (91.2 ± 7.7%) of the PPSF group are significantly higher than that in the MWPSF group (P < 0.05). And the total blood loss (TBL) of the PPSF group (477.6 ± 228.8 ml) is also more than that in the MWPSF group (401.0 ± 171.3 ml). CONCLUSIONS: Our results suggest that in the minimally invasive surgical treatment of thoracolumbar fractures, the perioperative HBL is much higher than visible blood loss (VBL). Although PPSF has less intraoperative blood loss, it has higher TBL and HBL than those of MWPSF. Compared with MWPSF, we should pay more attention to the postoperative anemia status of patients with thoracolumbar fractures undergoing PPSF surgery.

Lathyrane diterpenoids from Euphorbia lathyris induce cell-cycle arrest and apoptosis in human hypertrophic scar cells.

One new lathyrane-type diterpenoid, euphlathin A (1), and 11 known analogues (2-12), were isolated from the fruits of Euphorbia lathyris. Their structures were elucidated by spectroscopic data. The absolute configurations of 1 were established by single-crystal X-ray crystallography. All diterpenoids (1-12) were evaluated for antiproliferative activity against the human hypertrophic scar (HTS) cells. Compound 1 exhibited significantly against HTS cells growth with an IC50 value of 6.33 µM. Morphological features of apoptosis were evaluated in 1-treated HTS cells. Wound healing assays indicated that 1 significantly inhibited the migration of HTS at 24 h and 48 h. Compound 1 effectively induced apoptosis of HTS, which was associated with G2/M or S phase cell cycle arrest. Flow cytometric analysis showed that the treatment by 1 significantly induced HTS cell apoptosis in a dose-dependent manner. Overall, euphlathin A (1) has the potential to be a therapeutic agent for the treatment of hyperplastic scar therapy.

Buried Interface Dielectric Layer Engineering for Highly Efficient and Stable Inverted Perovskite Solar Cells and Modules.

Stability and scalability are essential and urgent requirements for the commercialization of perovskite solar cells (PSCs), which are retarded by the non-ideal interface leading to non-radiative recombination and degradation. Extensive efforts are devoted to reducing the defects at the perovskite surface. However, the effects of the buried interface on the degradation and non-radiative recombination need to be further investigated. Herein, an omnibearing strategy to modify buried and top surfaces of perovskite film to reduce interfacial defects, by incorporating aluminum oxide (Al2 O3 ) as a dielectric layer and growth scaffolds (buried surface) and phenethylammonium bromide as a passivation layer (buried and top surfaces), is demonstrated. Consequently, the open-circuit voltage is extensively boosted from 1.02 to 1.14 V with the incorporation of Al2 O3 filling the voids between grains, resulting in dense morphology of buried interface and reduced recombination centers. Finally, the impressive efficiencies of 23.1% (0.1 cm2 ) and 22.4% (1 cm2 ) are achieved with superior stability, which remain 96% (0.1 cm2 ) and 89% (1 cm2 ) of its initial performance after 1200 (0.1 cm2 ) and 2500 h (1 cm2 ) illumination, respectively. The dual modification provides a universal method to reduce interfacial defects, revealing a promising prospect in developing high-performance PSCs and modules.

Safety and Efficacy of Long-Acting Injectable Agents for HIV-1: Systematic Review and Meta-Analysis.

BACKGROUND: HIV-1 infection continues to affect global health. Although antiretrovirals can reduce the viral load or prevent HIV-1 infection, current drugs require daily oral use with a high adherence level. Long-acting antiretrovirals (LA-ARVs) significantly improve medication adherence and are essential for HIV-1 prophylaxis and therapy. OBJECTIVE: This study aimed to investigate the safety and efficacy of long-acting cabotegravir (CAB-LA) and long-acting rilpivirine (RPV-LA) in the prevention and treatment of HIV-1 infection. METHODS: PubMed, Embase, and the Cochrane Library were searched for studies from database inception to November 12, 2022. We included studies that reported efficacy and safety data on LA-ARV intervention in people living with HIV and excluded reviews, animal studies, and articles with missing or duplicate data. Virological suppression was defined as plasma viral load <50 copies/mL 6 months after antiviral therapy initiation. We extracted outcomes for analysis and expressed dichotomous data as risk ratios (RRs) and continuous data as mean differences. Depending on the heterogeneity assessment, a fixed- or random-effects model was used for data synthesis. We performed subgroup analyses of the partial safety and efficacy outcomes of CAB-LA+RPV-LA. The protocol was registered with the Open Science Framework. RESULTS: We included 12 trials comprising 10,957 individuals, of which 7 were prevention trials and 5 were treatment trials. CAB-LA and RPV-LA demonstrated safety profiles comparable with those of the placebo in terms of adverse event-related withdrawal. Moreover, the efficacy data showed that CAB-LA had a better effect on HIV-1 prevention than tenofovir disoproxil fumarate-emtricitabine (17/5161, 0.33% vs 75/5129, 1.46%; RR 0.21, 95% CI 0.07-0.61; I2=70%). Although CAB-LA+RPV-LA had more drug-related adverse events (556/681, 81.6% vs 37/598, 6.2%; RR 12.50, 95% CI 3.98-39.23; I2=85%), a mild or moderate injection site reaction was the most common reaction, and its frequency decreased over time. The efficacy of CAB-LA+RPV-LA was comparable with that of daily oral drugs at 48 and 96 weeks (1302/1424, 91.43% vs 915/993, 92.2%; RR 0.99, 95% CI 0.97-1.02; I2=0%), and a high level of virological suppression of 80.9% (186/230) was maintained even after 5 years of LA-ARV use. Similar efficacy outcomes were observed in both treatment-naive and treatment-experienced patients (849/911, 93.2% vs 615/654, 94%; RR 0.99, 95% CI 0.96-1.02; I2=0%). According to the questionnaires, more than 85% of people living with HIV favored LA-ARVs. CONCLUSIONS: LA-ARVs showed favorable safety profiles for both the prevention and treatment of HIV-1 infection and were well tolerated. CAB-LA has more satisfactory efficacy than tenofovir disoproxil fumarate-emtricitabine, significantly reducing the rate of HIV-1 infection. CAB-LA+RPV-LA maintains virological suppression for a long time and may be a viable switching strategy with enhanced public health benefits by reducing transmission. However, further trials are required to confirm the efficacy of these drugs.

miR-148a-3p facilitates osteogenic differentiation of fibroblasts in ankylosing spondylitis by activating the Wnt pathway and targeting DKK1.

Ankylosing spondylitis (AS) is a chronic inflammatory form of arthritis. MicroRNAs (miRNAs) have been identified to serve as therapeutic targets in various inflammatory diseases. The aim of the present study was to determine the functional mechanism of miR-148a-3p on AS. Specimens were collected from AS patients and non-AS patients. Fibroblasts were delivered with the aid of miR-148a-3p inhibitor. Cell staining was performed to observe the morphological changes, calcified nodules, and mineralization degree. The binding sites of miR-148a-3p and DKK1 were predicted on the Starbase website and subsequently verified by means of dual-luciferase reporter assay. AS fibroblasts with silenced miR-148a-3p were transfected with si-DKK1. Levels of RUNX2 and Osteocalcin, DKK1 and Wnt1 protein and phosphorylation level of ß-catenin were detected by means of western blot analysis. Results of the present study denoted that AS upregulated miR-148a-3p in fibroblasts to exacerbate osteogenic differentiation, resulting in increased calcified nodules and mineralization degree. Silencing miR-148a-3p could reverse the upregulation of RUNX2 and Osteocalcin in AS fibroblasts and reduce the calcified nodules and mineralization degree. miR-148a-3p targeted DKK1. DKK1 knockdown averted the effect of silencing miR-148a-3p in AS fibroblasts. In addition, silencing miR-148a-3p reversed the upregulation of Wnt1 and ß-catenin proteins in AS fibroblasts. To conclude, miR-148a-3p exacerbated the osteogenic differentiation of AS fibroblasts by inhibiting DKK1 expression and activating the Wnt pathway.