HPV integration: a precise biomarker for detection of residual/recurrent disease after treatment of CIN2-3.

BACKGROUND: This study aimed to investigate whether persistent human papillomavirus integration at the same loci (PHISL) before and after treatment can predict recurrent/residual disease in women with CIN2-3. METHODS: A total of 151 CIN2-3 women treated with conization between August 2020 and September 2021 were included. To investigate the precision of HPV integration, we further analyzed HPV integration-positive patients. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and the Youden index for predicting recurrence/residual disease were calculated. RESULTS: Among the 151 enrolled CIN2-3 women, 56 were HPV integration-positive and 95 had HPV integration-negative results. Six (10.7%) experienced recurrence among 56 HPV integration-positive patients, which was more than those in HPV integration-negative patients (one patient, 1.1%). In the 56 HPV integration-positive patients, 12 had positive HPV results after treatment, seven had PHISL, and two had positive cone margin. Among the seven patients who tested with PHISL, six (85.7%) had residual/recurrent disease. PHISL was a prominent predictor of persistent/recurrent disease. The HPV test, the HPV integration test, and PHISL all had a sensitivity of 100% and a NPV of 100% for residual/recurrent disease. PHISL showed better specificity (98.0% vs. 82.0%, p = 0.005) and PPV (85.7% vs. 40.0%, p = 0.001) than the HPV test for predicting recurrence. CONCLUSIONS: The HPV-integration-positive CIN2-3 women had much higher relapse rates than HPV-integration-negative CIN2-3 women. The findings indicate that PHISL derived from preoperative and postoperative HPV integration tests may be a precise biomarker for the identification of residual/recurrent CIN 2/3.

A case report of right-sided heart failure secondary to JAK2-mutation Loeffler endocarditis.

Loeffler's endocarditis (LE) is the cardiac manifestation of hypereosinophilic syndrome. We present a case of LE in a 45-year-old female, resulting in diffuse endothelial fibrosis and severe right-sided heart failure. The patient was admitted with dyspnoea and oedema, with haematology revealing an absolute eosinophil count of 20.9 × 109. Imaging showed near-complete obliteration of the right ventricular apical and formation of thromboses. Endomyocardial biopsy indicated diffuse fibrous hyperplasia of the endocardium with fibrinous thrombi rich in eosinophils. Molecular and cytogenetic analyses of bone marrow cells showed no signs of FIP1L1-PDGFRA fusion, PDGFRB mutation, abnormal myeloid maturation, or a lymphoproliferative disorder. Flow cytometry indicated no clonality, ruling out chronic eosinophilic leukaemia. Gene mutation screening discovered a p.L583_A586delinesS mutation in the JAK2 gene. Following treatment with ruxolitinib, the patient's eosinophil levels normalized, but unfortunately, the damage to the heart was irreversible. The patient was hospitalized multiple times due to right heart failure and resistance to diuretics. After thorough discussions with the medical team, it was determined that a heart transplantation would be the most effective treatment. Following the surgery, the patient successfully navigated the postoperative critical period with the support of an intra-aortic balloon pump (IABP), continuous renal replacement therapy (CRRT), and ventilator-assisted ventilation but subsequently developed an acquired Intensive care unit-acquired weakness (ICU-AW) and a depressive state. Fortunately, the patient gradually recovered from these complications.

Highlighting immune features of the tumor ecosystem and prognostic value of Tfh and Th17 cell infiltration in head and neck squamous cell carcinoma by single-cell RNA-seq.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) typically present with a complex anatomical distribution, often accompanied by insidious symptoms. This combination contributes to its high incidence and poor prognosis. It is now understood that the immune features of cellular components within the tumor ecosystem and their complex interactions are critical factors influencing both tumor progression and the effective immune response. METHODS: We obtained single-cell RNA sequencing data of 26,496 cells from three tumor tissues and five normal tissues and performed subsequent analyses. Immunohistochemical staining on tumor sections was used to validate the presence of malignant cells. Additionally, we included bulk RNA sequencing data from 502 HNSCC patients. Kaplan-Meier analysis and the log-rank test were employed to assess predictors of patient outcomes. RESULTS: We identified three epithelial subclusters exhibiting immune-related features. These subclusters promoted the infiltration of T cells, dendritic cells, and monocytes into the tumor microenvironment. Additionally, cancer-associated fibroblasts displayed tumor-promoting and angiogenesis characteristics, contrasting with the predominant antigen-presenting and inflammatory roles observed in fibroblasts from normal tissues. Furthermore, tumor endothelial subsets exhibited a double-sided effect, promoting tumor progression and enhancing the effectiveness of immune response. Finally, follicular helper T cells and T helper 17 cells were found to be significantly correlated with improved outcomes in HNSCC patients. These CD4+ T cell subpopulations could promote the anti-tumor immune response by recruiting and activating B and T cells. CONCLUSION: Our findings provide deeper insights into the immune features of the tumor ecosystem and reveal the prognostic significance of follicular helper T cells and T helper 17 cells. These findings may pave the way for the development of therapeutic approaches.

Fast, high-quality, and unshielded 0.2 T low-field mobile MRI using minimal hardware resources.

OBJECTIVE: To propose a deep learning-based low-field mobile MRI strategy for fast, high-quality, unshielded imaging using minimal hardware resources. METHODS: Firstly, we analyze the correlation of EMI signals between the sensing coil and the MRI coil to preliminarily verify the feasibility of active EMI shielding using a single sensing coil. Then, a powerful deep learning EMI elimination model is proposed, which can accurately predict the EMI components in the MRI coil signals using EMI signals from at least one sensing coil. Further, deep learning models with different task objectives (super-resolution and denoising) are strategically stacked for multi-level post-processing to enable fast and high-quality low-field MRI. Finally, extensive phantom and brain experiments were conducted on a home-built 0.2 T mobile brain scanner for the evaluation of the proposed strategy. RESULTS: 20 healthy volunteers were recruited to participate in the experiment. The results show that the proposed strategy enables the 0.2 T scanner to generate images with sufficient anatomical information and diagnostic value under unshielded conditions using a single sensing coil. In particular, the EMI elimination outperforms the state-of-the-art deep learning methods and numerical computation methods. In addition, 2 × super-resolution (DDSRNet) and denoising (SwinIR) techniques enable further improvements in imaging speed and quality. DISCUSSION: The proposed strategy enables low-field mobile MRI scanners to achieve fast, high-quality imaging under unshielded conditions using minimal hardware resources, which has great significance for the widespread deployment of low-field mobile MRI scanners.

The efficacy of and user satisfaction with different antiandrogens in Chinese transgender women.

Objective: Cyproterone acetate (CPA) and spironolactone (SPL) are different antiandrogens in gender-affirming hormone therapy (GAHT) for transgender women. Few studies have evaluated their efficacy and user satisfaction, especially among East Asians. This study aimed to evaluate these aspects in Chinese transgender women. Methods: Data were collected retrospectively from transgender women visiting the Peking University Third Hospital from 2012 to 2021. From 639 people identified as transgender women, 151 of them (80 using CPA and 71 using SPL, 16 to 40-year-old) under stable GAHT ≥6 months were enrolled. Total testosterone levels and visual analogue scale (VAS)-based satisfaction scores were evaluated. Results: No difference was observed in age between the CPA and SPL groups (median [IQR], 22 [20-24] years and 23 [20-26] years, respectively). The duration of GAHT was longer in CPA group than in SPL group (18 [10-32] months vs. 12 [8-21] months, p = 0.009). Total testosterone levels were significantly lower with CPA treatment (25 mg/d) than with SPL treatment (100 mg/d) (median [IQR]: 0.7 [0.7-2.1] nmol/L vs. 13.0 [6.0-17.8] nmol/L, p < 0.001). The proportion of total testosterone levels reaching the recommended range was significantly higher in CPA group than in SPL group (75.0% vs. 11.3%, p < 0.001). VAS-based satisfaction scores for erection decreased and figure feminization were higher in CPA group than in SPL group, which remained unchanged after adjusting for age, treatment duration, estradiol dose, and comorbid mental disorders (p < 0.05). The prolactin levels were higher in CPA group than in SPL group (18.9 [11.8-28.1] ng/ml vs. 11.8 [7.9-18.4] ng/ml, p < 0.001). No severe safety events were reported in both groups. Conclusion: In Chinese transgender women, CPA was more effective than SPL in lowering testosterone levels. Additionally, VAS scores indicated greater satisfaction with erection decreased and figure feminization using CPA compared to SPL.

A Nanoreactor Based on Metal-Organic Frameworks With Triple Synergistic Therapy for Hepatocellular Carcinoma.

The transformation of monotherapy into multimodal combined targeted therapy to fully exploit synergistic efficacy is of increasing interest in tumor treatment. In this work, a novel nanodrug-carrying platform based on iron-based MOFs, which is loaded with doxorubicin hydrochloride (DOX), dihydroartemisinin (DHA), and glucose oxidase (GOx), and concurrently covalently linked to the photosensitizer 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP) in polydopamine (PDA)-encapsulated MIL-101(Fe) (denoted as MIL-101(Fe)-DOX-DHA@TCPP/GOx@PDA, MDDTG@P), is successfully developed. Upon entering the tumor microenvironment, MDDTG@P catalyzes the hydrogen peroxide (H2O2) into hydroxyl radicals (·OH) and depletes glutathione (GSH); thus, exerting the role of chemodynamic therapy (CDT). The reduced Fe2+ can also activate DHA, further expanding CDT and promoting tumor cell apoptosis. The introduced GOx will rapidly consume glucose and oxygen (O2) in the tumor; while, replenishing H2O2 for Fenton reaction, starving the cancer cells; and thus, realizing starvation and chemodynamic therapy. In addition, the covalent linkage of TCPP endows MDDTG@P with good photodynamic therapeutic (PDT) properties. Therefore, this study develops a nanocarrier platform for triple synergistic chemodynamic/photodynamic/starvation therapy, which has promising applications in the efficient treatment of tumors.

Pullulan Polysaccharide as an Eco-Friendly Depressant for Flotation Separation of Chalcopyrite and Molybdenite.

It is difficult to separate molybdenite and chalcopyrite by froth flotation due to the good floatability of the two minerals. In this paper, the separation of copper-molybdenum sulfide minerals was realized by using pullulan polysaccharide (PU) as the depressant. The flotation test results showed that the copper concentrate grade increased from 16.24 to 29.86%, and the copper concentrate recovery reached 83.55% under low alkali conditions. The selective separation mechanism of the two minerals by PU was revealed through contact angle measurements, ζ-potential measurements, Fourier transform infrared (FTIR) spectroscopy analyses, and X-ray photoelectron spectroscopy (XPS) analyses. The ζ-potential and contact angle results showed that PU is more easily adsorbed on molybdenite to strengthen the hydrophilicity of molybdenite. The FTIR and XPS results showed that PU is adsorbed on molybdenite by physical interactions, and hydrophobic interactions and hydrogen bonding play a major role.

Gut microbiota mediates ambient PM2.5 exposure-induced abnormal glucose metabolism via short-chain fatty acids.

PM2.5 exposure has been found to cause gut dysbiosis and impair glucose homeostasis in human and animals, yet their underlying biological connection remain unclear. In the present study, we aim to investigate the biological significance of gut microbiota in PM2.5-induced glucose metabolic abnormalities. Our results showed that microbiota depletion by antibiotics treatment significantly alleviated PM2.5-induced glucose intolerance and insulin resistance, as indicated by the intraperitoneal glucose tolerance test, glucose-induced insulin secretion, insulin tolerance test, insulin-induced phosphorylation levels of Akt and GSK-3ß in insulin sensitive tissues. In addition, faecal microbiota transplantation (FMT) from PM2.5-exposed donor mice successfully remodeled the glucose metabolism abnormalities in recipient mice, while the transplantation of autoclaved faecal materials did not. Faecal microbiota analysis demonstrated that the composition and alpha diversity of the gut bacterial community were altered by PM2.5 exposure and in FMT recipient mice. Furthermore, short-chain fatty acids levels analysis showed that the circulating acetate was significantly decreased in PM2.5-exposed donor and FMT recipient mice, and supplementation of sodium acetate for 3 months successfully improved the glucose metabolism abnormalities induced by PM2.5 exposure. These results indicate that manipulating gut microbiota or its metabolites could be a potential strategy for preventing the adverse health effects of ambient PM2.5.

Biomimetic nanomedicine cocktail enables selective cell targeting to enhance ovarian Cancer chemo- and immunotherapy.

Ovarian cancer is one of the deadliest cancers, and combined chemo- and immunotherapies are potential strategies to combat it. However, the anti-cancer efficacy of the combined therapies may be limited by the non-selective co-delivery of chemotherapy and immunotherapy. Herein, a combined chemo- and immunotherapy is designed to selectively target ovarian tumor (ID8) cells and dendritic cells (DCs) using ID8 cell membrane (IM) and bacterial outer membrane vesicles (OMVs), respectively. Doxorubicin (DOX) and Ovalbumin (OVA) peptide (OVA257-264) are chosen as model chemotherapy and immunotherapy agents, respectively. A DNA nanocube capable of easily loading DOX or OVA257-264 is chosen as the carrier. Firstly, the DNA nanocube is used to load DOX or OVA257-264 to prepare cube-DOX or cube-OVA. This nanocube was then encapsulated with IM to form IM@Cube-DOX and with OMV to form OMV@Cube-OVA. IM@Cube-DOX can be selectively taken up by ID8 cells, leading to effective cell killing, while OMV@Cube-OVA targets and activates DC2.4 cells in vitro. Both IM@Cube-DOX and OMV@Cube-OVA show increased accumulation at ID8 tumors in C57BL/6 mice. Combined IM@Cube-DOX + OMV@Cube-OVA therapy demonstrates better anti-tumor efficacy than non-selective delivery methods such as OMV@(Cube-DOX + Cube-OVA) or IM@(Cube-DOX + Cube-OVA) in ID8-OVA tumor-bearing mice. In conclusion, this study demonstrates a biomimetic delivery strategy that enables selective drug delivery to tumor cells and DCs, thereby enhancing the anti-tumor efficacy of combined chemo- and immunotherapy through the selective delivery strategy.

PtbNet: Based on Local Few-Shot Classes and Small Objects to accurately detect PTB.

Pulmonary Tuberculosis (PTB) is one of the world's most infectious illnesses, and its early detection is critical for preventing PTB. Digital Radiography (DR) has been the most common and effective technique to examine PTB. However, due to the variety and weak specificity of phenotypes on DR chest X-ray (DCR), it is difficult to make reliable diagnoses for radiologists. Although artificial intelligence technology has made considerable gains in assisting the diagnosis of PTB, it lacks methods to identify the lesions of PTB with few-shot classes and small objects. To solve these problems, geometric data augmentation was used to increase the size of the DCRs. For this purpose, a diffusion probability model was implemented for six few-shot classes. Importantly, we propose a new multi-lesion detector PtbNet based on RetinaNet, which was constructed to detect small objects of PTB lesions. The results showed that by two data augmentations, the number of DCRs increased by 80% from 570 to 2,859. In the pre-evaluation experiments with the baseline, RetinaNet, the AP improved by 9.9 for six few-shot classes. Our extensive empirical evaluation showed that the AP of PtbNet achieved 28.2, outperforming the other 9 state-of-the-art methods. In the ablation study, combined with BiFPN+ and PSPD-Conv, the AP increased by 2.1, APs increased by 5.0, and grew by an average of 9.8 in APm and APl. In summary, PtbNet not only improves the detection of small-object lesions but also enhances the ability to detect different types of PTB uniformly, which helps physicians diagnose PTB lesions accurately. The code is available at https://github.com/Wenhui-person/PtbNet/tree/master.

Dual Nickel/Photoredox-Catalyzed Arylsulfonylation of Allenes.

The nickel/photoredox dual catalysis system is an efficient conversion platform for the difunctionalization of unsaturated hydrocarbons. Herein, we disclose the first dual nickel/photoredox-catalyzed intramolecular 1,2-arylsulfonylation of allenes, which can accurately construct a C(sp2)-C(sp2) bond and a C(sp3)-S bond. The reaction exhibits excellent chemoselectivity and regioselectivity, allowing modular conformations of a diverse series of 3-sulfonylmethylbenzofuran derivatives. Control experiments showed that the bipyridine ligand is crucial for the formation of a stable σ-alkyl nickel intermediate, providing the possibility for sulfonyl radical insertion. Meanwhile, the electrophilic sulfonyl radical facilitates further oxidative addition of the σ-alkyl nickel intermediate and inhibits addition with allenes. In addition, control experiments, cyclic voltammetry tests, Stern-Volmer experiments, and density functional theory calculations afford evidence for the Ni(0)/Ni(I)/Ni(II)/Ni(III) pathway in this 1,2-arylsulfonylation.

Silver-catalyzed P-centered anion nucleophilic addition to isocyanide: access to 2-phosphinoyl indoles/indol-3-ols.

A silver-catalyzed chemoselective cascade nucleophilic addition of a P-centered anion to isocyanides and cyclization reaction was developed for the efficient and practical synthesis of a wide range of 2-phosphinoyl indole and indol-3-ol derivatives. Unlike the well-documented synthesis of phosphorus-functionalized heterocycles via a P-centered radical, an anionic reactivity profile of phosphine oxides is most likely involved in this domino transformation.

Mice fatal pneumonia model induced by less-virulent Streptococcus pneumoniae via intratracheal aerosolization.

Aim: Animal models of fatal pneumonia caused by Streptococcus pneumoniae (Spn) have not been reliably generated using many strains of less virulent serotypes.Materials & methods: Pulmonary infection of a less virulent Spn serotype1 strain in the immunocompetent mice was established via the intratracheal aerosolization (ITA) route. The survival, local and systemic bacterial spread, pathological changes and inflammatory responses of this model were compared with those of mice challenged via the intratracheal instillation, intranasal instillation and intraperitoneal injection routes.Results: ITA and intratracheal instillation both induced fatal pneumonia; however, ITA resulted in better lung bacterial deposition and distribution, pathological homogeneity and delivery efficiency.Conclusion: ITA is an optimal route for developing animal models of severe pulmonary infections.

What is this article about? Streptococcus pneumoniae (Spn), a type of bacteria, can cause serious illness and death in otherwise healthy people. One way that we study pneumonia is using animals. However, pneumonia in animals infected with Spn in the laboratory does not mimic that in humans very well. To study this illness, we need a new way to set up a proper animal model.What were the results? This study set up a method called intratracheal aerosolization (ITA). In ITA, bacteria can form small droplets called aerosols and reach the deepest parts of a mouse's lung. ITA can cause deadly illness in mice infected with Spn, even if the mice are healthy.What do the results of the study mean? The ITA method could be a useful tool to set up animal models of serious pneumonia with less virulent bacteria.

Securinine inhibits carcinogenesis in gastric cancer by targeting AURKA-ß-catenin/Akt/STAT3 and the cell cycle pathway.

BACKGROUND: Gastric cancer (GC) is difficult to treat with currently available treatments. Securinine (SCR) has a lengthy history of use in the treatment of disorders of the nervous system, and its anticancer potential has been gaining attention in recent years. The aim of this study was to explore the repressive effect of SCR on GC and its fundamental mechanism. METHODS: The efficacy of SCR in GC cells was detected by MTT assays. Colony formation, flow cytometry and Transwell assays were used to assess the changes in the proliferation, apoptosis, cell cycle distribution, migration and invasion of GC cells after treatment. AGS (human gastric carcinoma cell)-derived xenografts were used to observe the effect of SCR on tumor growth in vivo. The molecular mechanism of action of SCR in GC was explored via RNA sequencing, bioinformatics analysis, Western blotting, molecular docking, and immunohistochemistry. RESULTS: SCR was first discovered to inhibit the proliferation, migration, and invasion of GC cells while initiating apoptosis and cell cycle arrest in vitro. It was also established that SCR has excellent anticancer effects in vivo. Interestingly, AURKA acts as a crucial target of SCR, and AURKA expression can be blocked by SCR. Moreover, this study revealed that SCR suppresses the cell cycle and the ß-catenin/Akt/STAT3 pathways, which were previously reported to be regulated by AURKA. CONCLUSION: SCR exerts a notable anticancer effect on GC by targeting AURKA and blocking the cell cycle and ß-catenin/Akt/STAT3 pathway. Thus, SCR is a promising pharmacological option for the treatment of GC.

PD-1 antibody in combination with chemotherapy for the treatment of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum: Two case reports.

BACKGROUND: SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting (SWI/SNF) complexes and plays an essential role in oncogenesis. SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis. There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies. Programmed death 1 (PD-1) antibodies, known as immune checkpoint inhibitor antibodies, potentially play a role in treating gastrointestinal tract malignancies. CASE SUMMARY: We present two patients with SMARCA4 deficiency and TP53 gene mutation in advanced undifferentiated carcinomas of the duodenum. For both patients, SMARCA4 deficiency was confirmed by immunohistochemical staining for the BRG1 protein, while TP53 gene mutations were observed via next-generation sequencing. Both patients were administered chemotherapy in combination with an anti-PD-1 antibody. The two patients exhibited completely different responses to treatment and had different prognoses. Case 1 experienced rapid progression after PD-1 infusion and chemotherapy, case 2 experienced a remarkable response after treatment, and the progression-free survival was more than 6 months. CONCLUSION: This study described our clinical and pathological observations of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum. PD-1 combined with chemotherapy showed a certain efficacy in select patients, providing options for treating these highly malignant tumors. Patients with liver metastases had a worse prognosis than did those with only lymph node metastasis.

Molecular Simulation Study on the Hydrogen Permeation Behavior and Mechanism of Common Polymers.

This research aimed to provide an understanding of the selection and safe application of pipeline liner materials for hydrogen transport by examining the permeation properties and mechanisms of hydrogen within polymers commonly used for this purpose, such as high-density polyethylene (HDPE) and ethylene-vinyl alcohol copolymer (EVOH), through molecular simulation. The study was carried out within defined operational parameters of temperature (ranging from room temperature to 80 °C) and pressure (from 2.5 to 10 MPa) that are pertinent to hydrogen pipeline infrastructures. The results reveal that with an increase in temperature from 30 °C to 80 °C, the solubility, diffusion, and permeability coefficients of hydrogen in HDPE increase by 18.7%, 92.9%, and 129.0%, respectively. Similarly, in EVOH, these coefficients experience increments of 15.9%, 81.6%, and 112.7%. Conversely, pressure variations have a negligible effect on permeability in both polymers. HDPE exhibits significantly higher hydrogen permeability compared to EVOH. The unique chain segment configuration of EVOH leads to the formation of robust hydrogen bonds among the hydroxyl groups, thereby impeding the permeation of hydrogen. The process by which hydrogen is adsorbed in polymers involves aggregation at low potential energy levels. During diffusion, the hydrogen molecule primarily vibrates within a limited range, with intermittent occurrences of significant hole-to-hole transitions over larger distances. Hydrogen exhibits a stronger interaction with HDPE compared to EVOH, leading to a higher number of adsorption sites and increased hydrogen adsorption capacity in HDPE. Hydrogen molecules move more actively in HDPE than in EVOH, exhibiting greater hole amplitude and more holes in transition during the diffusion process.

Arsenic field test kits based on solid-phase fluorescence filter effect induced by silver nanoparticle formation.

Millions of people worldwide are affected by naturally occurring arsenic in groundwater. The development of a low-cost, highly sensitive, portable assay for rapid field detection of arsenic in water is important to identify areas for safe wells and to help prioritize testing. Herein, a novel paper-based fluorescence assay was developed for the on-site analysis of arsenic, which was constructed by the solid-phase fluorescence filter effect (SPFFE) of AsH3-induced the generation of silver nanoparticles (AgNPs) toward carbon dots. The proposed SPFFE-based assay achieves a low arsenic detection limit of 0.36 µg/L due to the efficient reduction of Ag+ by AsH3 and the high molar extinction coefficient of AgNPs. In conjunction with a smartphone and an integrated sample processing and sensing platform, field-sensitive detection of arsenic could be achieved. The accuracy of the portable assay was validated by successfully analyzing surface and groundwater samples, with no significant difference from the results obtained through mass spectrometry. Compared to other methods for arsenic analysis, this developed system offers excellent sensitivity, portability, and low cost. It holds promising potential for on-site analysis of arsenic in groundwater to identify safe well locations and quickly obtain output from the global map of groundwater arsenic.

Rapid development of double-hit mRNA antibody cocktail against orthopoxviruses.

The Orthopoxvirus genus, especially variola virus (VARV), monkeypox virus (MPXV), remains a significant public health threat worldwide. The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes. mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production. Herein, by using the established lipid nanoparticle (LNP)-encapsulated mRNA platform, we constructed four mRNA combinations that encode monoclonal antibodies with broad neutralization activities against orthopoxviruses. In vivo characterization demonstrated that a single intravenous injection of each LNP-encapsulated mRNA antibody in mice resulted in the rapid production of neutralizing antibodies. More importantly, mRNA antibody treatments showed significant protection from weight loss and mortality in the vaccinia virus (VACV) lethal challenge mouse model, and a unique mRNA antibody cocktail, Mix2a, exhibited superior in vivo protection by targeting both intracellular mature virus (IMV)-form and extracellular enveloped virus (EEV)-form viruses. In summary, our results demonstrate the proof-of-concept production of orthopoxvirus antibodies via the LNP-mRNA platform, highlighting the great potential of tailored mRNA antibody combinations as a universal strategy to combat orthopoxvirus as well as other emerging viruses.

Electrochemical Azo-free Mitsunobu-type Reaction.

The classic chemical Mitsunobu reaction suffers from the need of excess alcohol activation reagents and the generation of significant by-products. Efforts to overcome these limitations have resulted in numerous creative solutions, but the substrate scope of these catalytic processes remains limited. Here we report an electrochemical Mitsunobu-type reaction, which features azo-free alcohol activation and broad substrate scope. This user-friendly technology allows a vast collection of heterocycles as the nucleophile, which can couple with a series of chiral cyclic and acyclic alcohols in moderate to high yields and excellent ee's. This practical reaction is scalable, chemoselective, uses simple Electrasyn setup with inexpensive electrodes and requires no precaution to exclude air and moisture. The synthetic utility is further demonstrated on the structural modification of diverse bioactive natural products and pharmaceutical derivatives and its straightforward application in a multiple-step synthesis of a drug candidate.

Portable purge and trap-microplasma optical emission spectrometric device for field detection of iodine in water.

Iodine is essential for human growth and can enter the body through food, water, and air. Analyzing its presence in the environment is crucial for ensuring healthy human development. However, current large-scale instruments have limitations in the field analysis of iodine. Herein, a miniaturized purge and trap point discharge microplasma optical emission spectrometric (P&T-µPD-OES) device was developed for the field analysis of iodine in water. Volatile iodine molecules were produced from total inorganic iodine (TII) through a basic redox reaction under acidic conditions, then the purge and trap module effectively separated and preconcentrated iodine molecules. The iodine molecules were subsequently atomized and excited by the integrated point discharge microplasma and an iodine atomic emission line at 206.24 nm was monitored by the spectrometer. Under optimal conditions, this proposed method had a detection limit of 16.2 µg L-1 for iodine and a precision better than 4.8%. Besides, the accuracy of the portable device was validated by successful analysis of surface and groundwater samples and a comparison of the mass spectrometry method. This proposed portable, low-power device is expected to support rapid access to iodine levels and distribution in water.