Basiliximab Treatment for Patients With Steroid-Refractory Acute Graft-Versus-Host Disease Following Matched Sibling Donor Hematopoietic Stem Cell Transplantation.

Basiliximab is an important treatment for steroid-refractory acute graft-versus-host disease (SR-aGVHD). We performed this retrospective study to evaluate the efficacy and safety of basiliximab treatment in SR-aGVHD patients following matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) (n = 63). Overall response rate (ORR) was 63.5% and 54% at any time and at day 28 after basiliximab treatment. Grade III-IV aGVHD before basiliximab treatment predicted a poor ORR after basiliximab treatment. The rates of virus, bacteria, and fungi infections were 54%, 23.8%, and 3.1%, respectively. With a median follow-up of 730 (range, 67-3,042) days, the 1-year probability of overall survival and disease-free survival after basiliximab treatment were 58.6% (95% confidence interval [CI] = 47.6%-72.2%) and 55.4% (95% CI = 44.3%-69.2%), respectively. The 3-year cumulative incidence of relapse and non-relapse mortality after basiliximab treatment were 18.9% (95% CI = 8.3%-29.5%) and 33.8% (95% CI = 21.8%-45.7%), respectively. Comorbidities burden before allo-HSCT, severity of aGVHD and liver aGVHD before basiliximab treatment showed negative influences on survival. Thus, basiliximab was safe and effective treatment for SR-aGVHD following MSD-HSCT.

Organoboron-Promoted Electrochemical Chlorosulfonylation of Alkenes with Sulfonyl Chlorides.

Although extraordinary advances have been achieved by the transition-metal catalysis system, there is an urgent need to explore and develop alternative methodologies that are more environmentally friendly. Herein, we report an electrochemical chlorosulfonylation of alkenes using a wide range of sulfonyl chlorides with an inexpensive, degradable, and commercially available organoboron as a promoter. Furthermore, this protocol employs convergent paired electrolysis, reducing the need for sacrificial anodes and minimizing the extent of hydrogen evolution.

Efficacy of cardiopulmonary rehabilitation nursing in enhancing pulmonary function, sleep quality, and living ability in COVID-19 patients.

OBJECTIVE: The purpose of this study was to elucidate the impact of cardiopulmonary rehabilitation nursing on the pulmonary function, sleep quality, and living ability of patients afflicted with Coronavirus Disease 2019 (COVID-19). METHODS: A total of 98 patients with COVID-19 treated at The People's Hospital of Guang'an between September 2021 and January 2023 were retrospectively collected as the research subjects. Among them, 48 patients who received standard nursing care from September 2021 to September 2022 were set as the control group, and 50 patients who underwent cardiopulmonary rehabilitation nursing from October 2022 to January 2023 were set as the research group. The pulmonary function indicators [including Forced Expiratory Volume in 1 second (FEV1) and Left Ventricular Ejection Fraction (LVEF)], sleep quality [evaluated using the Pittsburgh Sleep Quality Index (PSQI)], and living ability [assessed by the 36-Item Short Form Survey (SF-36) scale] pre- and post-intervention were compared between the two groups. RESULTS: Pre-intervention, FEV1, LVEF, PSQI scores, inflammatory factor levels [C-reactive protein (CRP), procalcitonin (PCT)], and SF-36 scores showed no significant differences between the two groups (P>0.05). Post-intervention, the research group exhibited notably enhanced FEV1 and LVEF, lower PSQI scores, lower CRP and PCT, and higher SF-36 scores compared with the control group, with statistical significance (P<0.05). Multifactorial logistic regression analysis showed that non-receipt of cardiopulmonary rehabilitation, age ≥60 years, concurrent respiratory failure, coexistent heart failure, and acid-base imbalance were independent risk factors of adverse outcomes in COVID-19 patients (P<0.05). CONCLUSION: Application of cardiopulmonary rehabilitation nursing in COVID-19 patients can significantly improve pulmonary function, sleep quality, and overall quality of life, and relieve the inflammatory state of the patients, thereby enhancing prognosis. This approach has certain value of popularization and application.

Effects of integrated nursing and psychological intervention on pain relief and patient satisfaction in urinary calculi patients.

OBJECTIVE: We aimed to assess the impact of integrated nursing and psychological intervention on pain intensity and patient satisfaction in individuals with urinary calculi. METHODS: This retrospective study included 94 urological patients from the Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, between January 2020 and June 2022. Participants were divided into a control group (n=48), receiving routine nursing and psychological intervention, and a study group (n=46), receiving integrated nursing and psychological intervention. We compared pain intensity, pain relief rate, patient satisfaction, Numeric Rating Scale (NRS) score, Pittsburgh Sleep Quality Index (PSQI) score, Self-rating Depression Scale (SDS) score, Self-rating Anxiety Scale (SAS) score, and quality of life scores between the groups. RESULTS: The study group had shorter hospital stays and lower hospitalization costs than the control group (both P < 0.05). Pain relief and satisfaction rates were higher in the study group (both P < 0.05). Post-intervention, both groups showed significant reductions in NRS, PSQI, SDS, and SAS scores, with greater reductions in the study group (all P < 0.05). Quality of life scores increased in both groups, more so in the SG (P < 0.05). The study group also had fewer adverse events (P < 0.05). Both groups showed decreased serum creatinine and blood urea nitrogen levels post-intervention, with a more significant decline in the study group (P < 0.05). Education, marital status, and occupation were major factors influencing outcomes in urinary calculi patients. CONCLUSION: Integrated nursing and psychological intervention significantly alleviates pain, improves emotional well-being, enhances sleep quality, increases overall life quality, and contributes to high patient satisfaction among urinary calculi patients.

Clinical efficacy analysis of tip­flexible suctioning ureteral access sheath combined with disposable flexible ureteroscope to treat 2-4 cm renal stones.

PURPOSE: This study aims to evaluate the clinical efficacy of using a tip­flexible suctioning ureteral access sheath (TFS-UAS) in combination with a traditional ureteral access sheath (T-UAS) and a disposable flexible ureteroscope (DFU) for treating large renal stones (2-4 cm in diameter). METHODS: We retrospectively collected clinical data from 238 patients who underwent retrograde intrarenal surgery (RIRS) at Ganzhou People's Hospital between January 2019 and October 2023. The study included 238 patients who met the inclusion criteria, with 125 in the observation group using TFS-UAS and 113 in the control group using T-UAS. We compared differences in the stone-free rate (SFR), complication rates, surgery duration, and average hospital stay between the two groups. RESULTS: All 238 surgeries were successfully completed. The stone-free rates for the observation group at the first and thirtieth day post-surgery were 87.20% and 95.20%, respectively, whereas for the control group, the rates were 73.45% and 85.84%, showing statistically significant differences (P < 0.05). The overall complication rates were 1.6% for the observation group and 14.16% for the control group, also statistically significant (P < 0.001). The surgical times for stone removal were (101.17 ± 25.64) minutes for the observation group and (86.23 ± 20.35) minutes for the control group, with significant differences (P < 0.05). CONCLUSION: Compared to T-UAS, combining TFS-UAS with DFU for treating renal stones of 2-4 cm diameter, although more time-consuming, resulted in higher SFRs and improved safety.

Impact of Telemedicine on Blood Glucose Control and Ophthalmic Screenings for Patients with Diabetes in Remote Areas During the COVID-19 Pandemic: A Real-World Study in Northern Taiwan.

Introduction: The purpose of this study was to assess the impact of telemedicine on ophthalmic screening and blood glucose control for patients with diabetes in remote areas of Northern Taiwan during the coronavirus disease 2019 (COVID-19) pandemic. Methods: Telemedicine was implemented in Shiding and Wanli Districts using a 5G platform from April 2021 to December 2022. Patients with poorly controlled diabetes received real-time consultations from endocrinologists at Far Eastern Memorial Hospital, 50 km away, for medication adjustment, diet control, and lifestyle recommendations. The study also provided cloud-upload blood glucose meters for self-monitoring and regular medical advice from hospital nurses. Ophthalmic screenings included fundus imaging, external eye image, and intraocular pressure measurement, with instant communication and diagnosis by ophthalmologists through telemedicine. A satisfaction questionnaire survey was conducted. Results: The study enrolled 196 patients with diabetes. Blood glucose and glycosylated hemoglobin levels were significantly reduced after applying telemedicine (p = 0.01 and p = 0.005, respectively). Ophthalmic screenings led to hospital referrals for 16.0% with abnormal fundus images, 15.6% with severe cataract or anterior segment disorders, and 27.9% with ocular hypertension or glaucoma. Fundus screening rates remained high at 86.3% and 80.4% in 2022, mainly using telemedicine, comparable with the traditional screening rate in the past 5 years. The overall satisfaction rate was 98.5%. Conclusions: Telemedicine showed effectiveness and high satisfaction in managing diabetes and conducting ophthalmic screenings in remote areas during the COVID-19 pandemic. It facilitated early diagnosis and treatment of ocular conditions while maintaining good blood glucose control and fundus screening rates.

Chrysin mitigated neuropathic pain and peripheral sensitization in knee osteoarthritis rats by repressing the RAGE/PI3K/AKT pathway regulated by HMGB1.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic progressive osteoarthropathy. Chrysin's anti-KOA action has been demonstrated, however more research is needed to understand how chrysin contributes to KOA. METHODS: LPS/ATP-induced macrophages transfected with or without HMGB1 overexpression underwent 5 µg/mL chrysin. The cell viability and macrophage pyroptosis were examined by cell counting kit-8 and flow cytometer. In vivo experiments, rats were injected with 1 mg monosodium iodoacetate by the infrapatellar ligament of the bilateral knee joint to induce KOA. The histological damage was analyzed by Safranin O/Fast Green staining and hematoxylin and eosin staining. The PWT, PWL and inflammatory factors were analyzed via Von-Frey filaments, thermal radiometer and ELISA. Immunofluorescence assay examined the expressions of CGRP and iNOS. The levels of HMGB1/RAGE-, NLRP3-, PI3K/AKT- and neuronal ion channel-related markers were examined by qPCR and western blot. RESULTS: Chrysin alleviated macrophage pyroptosis by inhibiting HMGB1 and the repression of chrysin on HMGB1/RAGE pathway and ion channel activation was reversed by overexpressed HMGB1. HMGB1 facilitated neuronal ion channel activation through the RAGE/PI3K/AKT pathway. Chrysin could improve the pathological injury of knee joints in KOA rats. Chrysin suppressed the HMGB1-regulated RAGE/PI3K/AKT pathway, hence reducing KOA damage and peripheral sensitization. CONCLUSION: Chrysin mitigated neuropathic pain and peripheral sensitization in KOA rats by repressing the RAGE/PI3K/AKT pathway modulated by HMGB1.

Four weeks of off-treatment follow-up is sufficient to determine virologic responses at off-treatment week 12 in patients with hepatitis C virus infection receiving fixed-dose pangenotypic direct-acting antivirals.

Early confirmation of sustained virologic response (SVR) or viral relapse after direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection is essential based on public health perspectives, particularly for patients with high risk of nonadherence to posttreatment follow-ups. A total of 1011 patients who achieved end-of-treatment virologic response, including 526 receiving fixed-dose pangenotypic DAAs, and 485 receiving other types of DAAs, who had available off-treatment weeks 4 and 12 serum HCV RNA data to confirm SVR at off-treatment week 12 (SVR12) or viral relapse were included. The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 to predict patients with SVR12 or viral relapse were reported. Furthermore, we analyzed the proportion of concordance between SVR12 and SVR24 in 943 patients with available SVR24 data. The PPV and NPV of SVR4 to predict SVR12 were 98.5% (95% confidence interval [CI]: 98.0-98.9) and 100% (95% CI: 66.4-100) in the entire population. The PPV of SVR4 to predict SVR12 in patients receiving fixed-dose pangenotypic DAAs was higher than those receiving other types of DAAs (99.8% [95% CI: 98.9-100] vs. 97.1% [95% CI: 96.2-97.8], p < 0.001). The NPVs of SVR4 to predict viral relapse were 100%, regardless of the type of DAAs. Moreover, the concordance between SVR12 and SVR24 was 100%. In conclusion, an off-treatment week 4 serum HCV RNA testing is sufficient to provide an excellent prediction power of SVR or viral relapse at off-treatment week 12 among patients with HCV who are treated with fixed-dose pangenotypic DAAs.

Clinical Observations on the Combined Use of Hyperbaric Oxygenation and Conventional Medications in the Management of Type 2 Diabetes Mellitus Concurrent With Sudden Deafness.

Objective: The aim of this study is to investigate the effectiveness of combining hyperbaric oxygen therapy (HBOT) with conventional pharmacological interventions in the management of type 2 diabetes mellitus concurrent with sudden deafness. Methods: A cohort of 96 patients diagnosed with sudden deafness was enrolled and subsequently randomized into 2 groups: a treatment group (n = 50) and a control group (n = 46). The control group received standard conventional treatment aimed at enhancing microcirculation and nutritional support for nerves, while the treatment group underwent conventional symptomatic treatment coupled with HBOT. The evaluation encompassed the monitoring of blood glucose and blood lipid levels, clinical efficacy, and absolute hearing threshold improvement in both groups. Results: Following the intervention, noteworthy reductions in blood glucose and blood lipid levels were observed in both groups compared to their respective pretreatment values. Furthermore, posttreatment values in the treatment group exhibited a statistically significant decrease in comparison to those in the control group (P < .05). On assessing clinical efficacy posttreatment, the treatment group demonstrated a significantly higher efficacy than the control group (P < .05). In addition, the absolute hearing thresholds in both groups exhibited a significant decrease posttreatment compared to baseline values. Notably, the treatment group displayed a statistically significant reduction in absolute hearing thresholds compared to the control group posttreatment (P < .05). Conclusion: The combined therapeutic approach utilizing hyperbaric oxygen exhibits effectiveness in mitigating auditory impairment among individuals manifesting sudden deafness concomitant with type 2 diabetes mellitus. Furthermore, this treatment approach is associated with a concurrent reduction in blood glucose and blood lipid levels.

Efficacy and safety of Piwei Peiyuan Prescription in the treatment of chronic atrophic gastritis: A multicenter, double-blind, double-simulated, randomized, controlled clinical trial.

The incidence of chronic atrophic gastritis (CAG) is on the rise due to the growing pressure in modern social life, increasing bad living habits and emotional disorders (such as anxiety and depression), and the aging of the population. Of note, digestive system diseases are the dominant diseases in the field of traditional Chinese medicine (TCM). Therefore, this study evaluated the efficacy and safety of Piwei Peiyuan Prescription, a TCM prescription, in the treatment of CAG through a multicenter, double-blind, randomized, controlled design. This research was organized by the Second Affiliated Hospital of Anhui University of TCM and simultaneously performed in 6 centers. A total of 120 CAG patients were included and randomized into 2 groups: group A (treatment with Piwei Peiyuan granules plus Weifuchun Simulant) and Group B (treatment with Weifuchun Tablets plus Piwei Peiyuan Simulant). These 2 groups were compared in terms of gastroscopy scores, TCM syndrome scores, and serological indicators at baseline and within 12 weeks after treatment. According to endoscopic biopsy for pathological observation, atrophy (2.56 ±â€…1.08 vs 3.00 ±â€…1.00, P = .028) and intestinal epithelial hyperplasia (1.00 ±â€…1.43 vs 1.69 ±â€…1.80, P = .043) scores were lower in group A than in group B. For the more, group A had higher effective rates for inflammation, atrophy, and intestinal metaplasia (IM) in various regions of the stomach, especially for atrophy/IM of the gastric angle (64%, P = .034) and atrophy/IM of the lesser curvature of gastric antrum (63%, P = .042) than group B. According to TCM syndrome scores, Piwei Peiyuan Prescription improved the scores of gastric distension (2.30 ±â€…1.13 vs 2.80 ±â€…0.99, P = .022), preference for warmth and pressure (1.44 ±â€…1.06 vs 1.36 ±â€…1.10, P = .041), and poor appetite and indigestion (0.78 ±â€…0.66 vs 1.32 ±â€…0.72, P = .018). GAS, MTL, and PGE2 expression was significantly elevated after treatment with Piwei Peiyuan Prescription (P < .001). Piwei Peiyuan Prescription is effective for CAG treatment with high safety.

Dual Starvations Induce Pyroptosis for Orthotopic Pancreatic Cancer Therapy through Simultaneous Deprivation of Glucose and Glutamine.

Pancreatic cancer is a highly fatal disease, and existing treatment methods are ineffective, so it is urgent to develop new effective treatment strategies. The high dependence of pancreatic cancer cells on glucose and glutamine suggests that disrupting this dependency could serve as an alternative strategy for pancreatic cancer therapy. We identified the vital genes glucose transporter 1 (GLUT1) and alanine-serine-cysteine transporter 2 (ASCT2) through bioinformatics analysis, which regulate glucose and glutamine metabolism in pancreatic cancer, respectively. Human serum albumin nanoparticles (HSA NPs) for delivery of GLUT1 and ASCT2 inhibitors, BAY-876/V-9302@HSA NPs, were prepared by a self-assembly process. This nanodrug inhibits glucose and glutamine uptake of pancreatic cancer cells through the released BAY-876 and V-9302, leading to nutrition deprivation and oxidative stress. The inhibition of glutamine leads to the inhibition of the synthesis of the glutathione, which further aggravates oxidative stress. Both of them lead to a significant increase in reactive oxygen species, activating caspase 1 and GSDMD and finally inducing pyroptosis. This study provides a new effective strategy for orthotopic pancreatic cancer treatment by dual starvation-induced pyroptosis. The study for screening metabolic targets using bioinformatics analysis followed by constructing nanodrugs loaded with inhibitors will inspire future targeted metabolic therapy for pancreatic cancer.

NIR-II Fluorescence Imaging for In Vivo Quantitative Analysis.

In vivo real-time qualitative and quantitative analysis is essential for the diagnosis and treatment of diseases such as tumors. Near-infrared-II (NIR-II, 1000-1700 nm) bioimaging is an emerging visualization modality based on fluorescent materials. The advantages of NIR-II region fluorescent materials in terms of reduced photon scattering and low tissue autofluorescence enable NIR-II bioimaging with high resolution and increasing depth of tissue penetration, and thus have great potential for in vivo qualitative and quantitative analysis. In this review, we first summarize recent advances in NIR-II imaging, including fluorescent probe selection, quantitative analysis strategies, and imaging. Then, we describe in detail representative applications to illustrate how NIR-II fluorescence imaging has become an important tool for in vivo quantitative analysis. Finally, we describe the future possibilities and challenges of NIR-II fluorescence imaging.

COVID-19 was associated with the complications after allogeneic hematopoietic stem cell transplantation.

We aimed to identify the severity and duration of COVID-19 infection on complications after allo-HSCT. Enrolled 179 hospitalized patients with COVID-19 were categorized into long-term infection (> 18 days, n = 90) or short-term infection group (≤ 18 days, n = 89) according to the median duration of COVID-19. The severity of COVID-19 was categorized as asymptomatic infection, mild, moderate, severe, and critical illness according to guidelines of National Institutes of Health. Particularly, severe illness and critical illness were classified as serious infection. Asymptomatic infection, mild illness and moderate illness were classified as non-serious infection. The 150-day probabilities of poor graft function (PGF), cytomegalovirus (CMV) pneumonia and non-relapse mortality (NRM) were significantly higher in long-term infection group. The 150-day probabilities of CMV pneumonia and NRM after COVID-19 were higher in serious infection group. The 150-day probabilities of overall survival (OS) was significantly lower in long-term and serious infection group. In multivariable analysis, the severity of COVID-19 was associated with NRM and OS, and the duration of COVID-19 was associated with PGF. In summary, our data reported that the severity and duration of COVID-19 were associated with several complications and contribute to poor outcomes after allo-HSCT.

miR-141-3p attenuates RSL3-induced ferroptosis and intestinal epithelial-mesenchymal transition via directly inhabits ZEB1 in intestinal Behçet's syndrome.

The aims of this study were to investigate whether the ferroptosis is involved in intestinal Behçet's syndrome (IBS), and to identify if miR-141-3p could attenuate RAS-selective lethal 3 (RSL3)-induced ferroptosis and intestinal epithelial to mesenchymal transition (EMT) via directly inhabits zinc fnger E-box binding homeobox 1 (ZEB1). The expressions of ferroptosis-related proteins in the intestinal tissues of patients with IBS were investigated by immunohistochemistry and quantitative real-time PCR (qRT-PCR). Malondialdehyde (MDA) contents of the intestinal tissues and cells were detected. Serum from IBS patients and RSL3 were co-cultured with intestinal epithelial cells in vitro. In order to investigate whether RSL3-induced ferroptosis can be ameliorated by miR-141-3p, the intestinal epithelial cells were firstly stimulated with RSL3 and then incubated with miR-141-3p mimics. Western blot was used to measure the expression of EMT and ferroptosis-related proteins. Expression of GPX4 (22.51% ± 2.05%, 51.75% ± 3.47%, t = - 7.77, p = 0.000) and xCT (17.49% ± 1.57%, 28.73% ± 1.75%, t = - 4.38, p = 0.003) were significantly lower in intestinal mucosal tissues of patients with IBS compared with HC group. Compared with the HC samples, the IBS specimens had significantly higher MDA (t = 4.32, p = 0.01). Moreover, the relative mRNA levels of ferritin light chain (FTL) (t = 4.07, p = 0.02) and ferritin heavy chain (FTH) (t = 8.82, p = 0.001) in the intestinal tissues were significant higher in IBS patients than in HC group. Serum from IBS patients could induce intestinal epithelial cell ferroptosis in vitro. Moreover, miR-141-3p could attenuate intestinal epithelial cell ferroptosis-induced by RSL3 and intestinal EMT via targeting ZEB1 in vitro. Ferroptosis were induced in patients with IBS. Moreover, the serum from IBS patients could induce ferroptosis in vitro. miR-141-3p could attenuate intestinal epithelial cell ferroptosis and intestinal EMT via targeting ZEB1. Therefore, miR-141-3p may open new avenues for the treatment of IBS in the future. Key Points • Ferroptosis in IBS is first reported in this study. • In this study, we explored that the serum from IBS patients could induce ferroptosis in vitro and miR-141-3p could attenuate intestinal epithelial cell ferroptosis and intestinal EMT via targeting ZEB1.

Efficient and selective external activator-free cobalt catalyst for hydroboration of terminal alkynes enabled by BiPyPhos.

Herein, a robust catalyst system, composed of a bipyridine-based diphosphine ligand (BiPyPhos) and a cobalt precursor Co(acac)2, is successfully developed and applied in the hydroboration of terminal alkynes, exclusively affording various versatile ß-E-vinylboronates in high yields at room temperature.

Comparison of diagnostic performance among Abbott RealTime HCV Genotyping II, Abbott HCV Genotype plus RUO, and Roche Cobas HCV Genotyping assays for hepatitis C virus genotyping.

Comparison of diagnostic accuracy for commercial hepatitis C virus (HCV) genotyping (Abbott RealTime HCV Genotyping II, Roche Cobas Genotyping) and investigational Abbott HCV Genotype plus RUO assays designed to discriminate genotype (GT)-1a, 1b or 6 in cases of ambiguous GT from the Abbott commercial assay remains limited. 743 HCV-viremic samples were subjected to analysis using Abbott and Roche commercial as well as Abbott HCV Genotype plus RUO assays. Next-generation sequencing (NGS) targeting core region was employed as the reference standard. Diagnostic accuracy was reported as the number of participants (percentages) along with 95% confidence intervals (CIs). Using NGS, 741 samples (99.7%) yielded valid genotyping results. The diagnostic accuracies were 97.6% (95% CI: 96.1%-98.5%) and 95.3% (95% CI: 93.4%-96.6%) using Abbott and Roche commercial assays (p = 0.0174). Abbott commercial assay accurately diagnosed HCV GT-6a and 6w, whereas Roche commercial assay accurately diagnosed HCV GT-6a. Both assays demonstrated low accuracies for HCV GT-6b, 6e, 6g, and 6n. Abbott HCV Genotype plus RUO assay discriminated 13 of the 14 samples (92.9%; 95% CI: 64.2%-99.6%) that yielded ambiguous GT. Both assays were capable of diagnosing mixed HCV infections when the minor genotype comprised >8.4% of the viral load. The diagnostic performance of commercial HCV genotyping assays is commendable. Abbott assay demonstrated superior performance compared to Roche assay in diagnosing HCV GT-6. Abbott HCV Genotype plus RUO assay aids in discriminating ambiguous GT. Both commercial assays are proficient in diagnosing mixed HCV infections at a cut-off viral load of 8.4% in minor genotype.

Development of an mRNA-based therapeutic vaccine mHTV-03E2 for high-risk HPV-related malignancies.

Human papillomavirus (HPV) 16 and 18 infections are related to many human cancers. Despite several preventive vaccines for high-risk (hr) HPVs, there is still an urgent need to develop therapeutic HPV vaccines for targeting pre-existing hrHPV infections and lesions. In this study, we developed a lipid nanoparticle (LNP)-formulated mRNA-based HPV therapeutic vaccine (mHTV)-03E2, simultaneously targeting the E2/E6/E7 of both HPV16 and HPV18. mHTV-03E2 dramatically induced antigen-specific cellular immune responses, leading to significant CD8+ T cell infiltration and cytotoxicity in TC-1 tumors derived from primary lung epithelial cells of C57BL/6 mice expressing HPV E6/E7 antigens, mediated significant tumor regression, and prolonged animal survival, in a dose-dependent manner. We further demonstrated significant T cell immunity against HPV16/18 E6/E7 antigens for up to 4 months post-vaccination in immunological and distant tumor rechallenging experiments, suggesting robust memory T cell immunity against relapse. Finally, mHTV-03E2 synergized with immune checkpoint blockade to inhibit tumor growth and extend animal survival, indicating the potential in combination therapy. We conclude that mHTV-03E2 is an excellent candidate therapeutic mRNA vaccine for treating malignancies caused by HPV16 or HPV18 infections.

Near-Unity Photoluminescence Quantum Yield of Core-Only InP Quantum Dots via a Simple Postsynthetic InF3 Treatment.

Indium phosphide (InP) quantum dots (QDs) are considered the most promising alternative for Cd and Pb-based QDs for lighting and display applications. However, while core-only QDs of CdSe and CdTe have been prepared with near-unity photoluminescence quantum yield (PLQY), this is not yet achieved for InP QDs. Treatments with HF have been used to boost the PLQY of InP core-only QDs up to 85%. However, HF etches the QDs, causing loss of material and broadening of the optical features. Here, we present a simple postsynthesis HF-free treatment that is based on passivating the surface of the InP QDs with InF3. For optimized conditions, this results in a PLQY as high as 93% and nearly monoexponential photoluminescence decay. Etching of the particle surface is entirely avoided if the treatment is performed under stringent acid-free conditions. We show that this treatment is applicable to InP QDs with various sizes and InP QDs obtained via different synthesis routes. The optical properties of the resulting core-only InP QDs are on par with InP/ZnSe/ZnS core-shell QDs, with significantly higher absorption coefficients in the blue, and with potential for faster charge transport. These are important advantages when considering InP QDs for use in micro-LEDs or photodetectors.

Green Manuring Enhances Soil Multifunctionality in Tobacco Field in Southwest China.

The use of green manure can substantially increase the microbial diversity and multifunctionality of soil. Green manuring practices are becoming popular for tobacco production in China. However, the influence of different green manures in tobacco fields has not yet been clarified. Here, smooth vetch (SV), hairy vetch (HV), broad bean (BB), common vetch (CV), rapeseed (RS), and radish (RD) were selected as green manures to investigate their impact on soil multifunctionality and evaluate their effects on enhancing soil quality for tobacco cultivation in southwest China. The biomass of tobacco was highest in the SV treatment. Soil pH declined, and soil organic matter (SOM), total nitrogen (TN), and dissolved organic carbon (DOC) content in CV and BB and activity of extracellular enzymes in SV and CV treatments were higher than those in other treatments. Fungal diversity declined in SV and CV but did not affect soil multifunctionality, indicating that bacterial communities contributed more to soil multifunctionality than fungal communities. The abundance of Firmicutes, Rhizobiales, and Micrococcales in SV and CV treatments increased and was negatively correlated with soil pH but positively correlated with soil multifunctionality, suggesting that the decrease in soil pH contributed to increases in the abundance of functional bacteria. In the bacteria-fungi co-occurrence network, the relative abundance of key ecological modules negatively correlated with soil multifunctionality and was low in SV, CV, BB, and RS treatments, and this was associated with reductions in soil pH and increases in the content of SOM and nitrate nitrogen (NO3--N). Overall, we found that SV and CV are more beneficial for soil multifunctionality, and this was driven by the decrease in soil pH and the increase in SOM, TN, NO3--N, and C- and N-cycling functional bacteria.