The design of metal oxide catalysts predominantly focuses on the composition or geometry engineering to enable optimized reactivity on the surface. Despite the numerous reports investigating the ...surface chemisorption of organic molecules on metal oxides, insights into how adsorption of organic modifiers can be exploited to optimize the catalytic properties of metal oxides are lacking. Herein, we describe the use of enolic acetylacetones to modify the surface Lewis acid properties of manganese oxide catalysts. The acetylacetone modification is stable under the reaction conditions and strongly influences the redox-acid cooperative catalysis of manganese oxides. This enables a rational control of the oxidation selectivity of structurally diverse arylmethyl amines to become switchable from nitriles to imines.
The Nucleocapsid Protein (NP) of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is not only the core structural protein required for viral packaging, but also participates in the ...regulation of viral replication, and its post‐translational modifications such as phosphorylation have been shown to be an important strategy for regulating virus proliferation. Our previous work identified NP could be ubiquitinated, as confirmed by two independent studies. But the function of NP ubiquitination is currently unknown. In this study, we first pinpointed TRIM6 as the E3 ubiquitin ligase responsible for NP ubiquitination, binding to NP's CTD via its RING and B‐box‐CCD domains. TRIM6 promotes the K29‐typed polyubiquitination of NP at K102, K347, and K361 residues, increasing its binding to viral genomic RNA. Consistently, functional experiments such as the use of the reverse genetic tool trVLP model and gene knockout of TRIM6 further confirmed that blocking the ubiquitination of NP by TRIM6 significantly inhibited the proliferation of SARS‐CoV‐2. Notably, the NP of coronavirus is relatively conserved, and the NP of SARS‐CoV can also be ubiquitinated by TRIM6, indicating that NP could be a broad‐spectrum anti‐coronavirus target. These findings shed light on the intricate interaction between SARS‐CoV‐2 and the host, potentially opening new opportunities for COVID‐19 therapeutic development.
Controlling the reaction selectivity of a heterobifunctional molecule is a fundamental challenge in many catalytic processes. Recent efforts to design chemoselective catalysts have focused on ...modifying the surface of metal nanoparticle materials having tunable properties. However, precise control over the surface properties of base-metal oxide catalysts remains a challenge. Here, we show that green modification of the surface with carboxylates can be used to tune the ammoxidation selectivity toward the desired products during the reaction of hydroxyaldehyde on manganese oxide catalysts. These modifications improve the selectivity for hydroxynitrile from 0 to 92% under identical reaction conditions. The product distribution of dinitrile and hydroxynitrile can be continuously tuned by adjusting the amount of carboxylate modifier. This property was attributed to the selective decrease in the hydroxyl adsorption affinity of the manganese oxides by the adsorbed carboxylate groups. The selectivity enhancement is not affected by the tail structure of the carboxylic acid.
Influenza vaccines for H7N9 subtype have shown low immunogenicity in human clinical trials. Using novel adjuvants might represent the optimal available option in vaccine development. In this study, ...we demonstrated that the using of the STING agonist cGAMP as a mucosal adjuvant is effective in enhancing humoral, cellular and mucosal immune responses of whole virus, inactivated H7N9 vaccine in mice. A single dose of immunization was able to completely protect mice against a high lethal doses of homologous virus challenge with an significant dose-sparing effect. We also found that intranasal co-administration of H7N9 vaccine with cGAMP could provide effective cross protection against H1N1, H3N2, and H9N2 influenza virus. Furthermore, cGAMP induced significantly higher nucleoprotein specific CD4
and CD8
T cells responses in immunized mice, as well as upregulated the IFN-γ and Granzyme B expression in the lung tissue of mice in the early stages post a heterosubtypic virus challenge. These results indicated that STING agonist cGAMP was expected to be an effective mucosal immune adjuvant for pre-pandemic vaccines such as H7N9 vaccines, and the cGAMP combined nasal inactivated influenza vaccine will also be a promising strategy for development of broad-spectrum influenza vaccines.
Although weight loss is common in nasopharyngeal carcinoma (NPC) patients receiving radiotherapy, the prognostic influence of weight loss and its impact modified by body mass index (BMI) are still ...unclear.
2433 NPC patients receiving radical radiotherapy at Sun Yat-sen University Cancer Center from November, 2000 to December, 2004 were enrolled. Weight change during radiation treatment was categorized into high weight loss (HWL) and low weight loss (LWL). The associations of HWL with overall survival (OS) and disease-specific survival (DSS) were analyzed by Cox regression.
Among underweight patients, HWL was independently associated with poor OS (hazard ratio HR, 2.06; 95% CI 1.36-3.11) and DSS (HR, 2.27; 95% CI 1.38-3.73), as compared with LWL, after adjusting for covariates. In normal weight patients, the impact of HWL on OS (HR, 1.47; 95% CI 1.19-1.80) and DSS (HR, 1.59; 95% CI 1.24-2.03) was moderate. Among overweight/obese patients, no significant association between HWL and OS (HR, 1.22; 95% CI 0.95-1.55), or DSS (HR, 1.23; 95% CI 0.93-1.64) was found.
Except for overweight/obese patients, high weight loss during radiation treatment was independently associated with poor survival in NPC. This impact was more prominent in the underweight patient group.
A high maternal triglyceride (mTG) level during early pregnancy is linked to adverse pregnancy outcomes, but the use of specific interventions has been met with limited success. A retrospective ...cohort study was designed to investigate the impact of gestational weight gain (GWG) on the relationship between high levels of mTG and adverse pregnancy outcomes in normal early pregnancy body mass index (BMI) women. The patients included 39,665 women with normal BMI who had a singleton pregnancy and underwent serum lipids screening during early pregnancy. The main outcomes were adverse pregnancy outcomes, including gestational hypertension, preeclampsia, gestational diabetes, cesarean delivery, preterm birth, and large or small size for gestational age (LGA or SGA) at birth. As a result, the high mTG (≥2.05mM) group had increased risks for gestational hypertension ((Adjusted odds ratio (AOR), 1.80; 95% CI, 1.46 to 2.24)), preeclampsia (1.70; 1.38 to 2.11), gestational diabetes (2.50; 2.26 to 2.76), cesarean delivery (1.22; 1.13 to 1.32), preterm birth (1.42, 1.21 to 1.66), and LGA (1.49, 1.33 to 1.68) compared to the low mTG group, after adjustment for potential confounding factors. Additionally, the risks of any adverse outcome were higher in each GWG subgroup among women with high mTG than those in the low mTG group. High mTG augmented risks of gestational hypertension, preeclampsia, preterm birth, and LGA among women with 50th or greater percentile of GWG. Interestingly, among women who gained less than the 50th percentile of GWG subgroups, there was no relationship between high mTG level and risks for those pregnancy outcomes when compared to low mTG women. Therefore, weight control and staying below 50th centile of the suggested GWG according to gestational age can diminish the increased risks of adverse pregnancy outcomes caused by high mTG during early pregnancy.
Background
Stereotactic body radiation therapy (SBRT) has gradually been recognized as favorable curative treatment for localized prostate cancer (PC). However, the high rate of erectile dysfunction ...(ED) after traditional photon‐based SBRT remains an ongoing challenge that greatly impacts the quality of life of PC survivors. Modern proton therapy allows higher conformal SBRT delivery and has the potential to reduce ED occurrence but its cost‐effectiveness remains uninvestigated.
Methods
A Markov decision model was designed to evaluate the cost‐effectiveness of proton SBRT versus photon SBRT in reducing irradiation‐related ED. Base‐case evaluation was performed on a 66‐year‐old (median age of PC) localized PC patient with normal pretreatment erectile function. Further, stratified analyses were performed for different age groups (50, 55, 60, 65, 70, and 75 years) and threshold analyses were conducted to estimate cost‐effective scenarios. A Chinese societal willingness‐to‐pay (WTP) threshold (37,653 US dollars $)/quality‐adjusted life‐year QALY) was adopted.
Results
For the base case, protons provided an additional 0.152 QALY at an additional cost of $7233.4, and the incremental cost‐effectiveness ratio was $47,456.5/QALY. Protons was cost‐effective for patients ≤62‐year‐old at the WTP of China (≤66‐year‐old at a WTP of $50,000/QALY; ≤73‐year‐old at a WTP of $100,000/QALY). For patients at median age, once the current proton cost ($18,000) was reduced to ≤$16,505.7 or the patient had a life expectancy ≥88 years, protons were cost‐effective at the WTP of China.
Conclusions
Upon assumption‐based modeling, the results of current study support the use of proton SBRT in younger localized PC patients who are previously potent, for better preservation of erectile function. The findings await further validation using data from future comparative clinical trials.
Background
Compared to conventional intensity‐modulated photon radiation therapy (IMRT), intensity‐modulated proton radiation therapy (IMPT) has potential to reduce irradiation‐induced late ...toxicities while maintaining excellent tumor control in patients with nasopharyngeal carcinoma (NPC). However, the relevant cost‐effectiveness remains controversial.
Methods
A Markov decision tree analysis was performed under the assumption that IMPT offered normal tissue complication probability reduction (NTCP reduction) in long‐term dysphagia, xerostomia, and hearing loss, compared to IMRT. Base‐case evaluation was performed on T2N2M0 NPC of median age (43 years old). A Chinese societal willingness‐to‐pay threshold (33558 US dollars $)/quality‐adjusted life‐year QALY) was adopted.
Results
For patients at median age and having NTCP reduction of 10%, 20%, 30%, 40%, 50%, and 60%, their incremental cost‐effectiveness ratios were $102684.0/QALY, $43161.2/QALY, $24134.7/QALY, $13991.6/QALY, $8259.8/QALY, and $4436.1/QALY, respectively; IMPT should provide an NTCP reduction of ≥24% to be considered cost‐effective.
Conclusions
IMPT has potential to be cost‐effective for average Chinese NPC patients and should be validated clinically.
Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines ...for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi‐disciplinary team comprising of experts from all sub‐specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence‐based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow‐up of NPC, which aim to improve the management of NPC.
The H7N9 influenza virus has been circulating in China for more than six years. The neuraminidase (NA) has gained great concern for the development of antiviral drugs, therapeutic antibodies, and new ...vaccines. In this study, we screened seven mouse monoclonal antibodies (mAbs) and compared their protective effects against H7N9 influenza virus. The epitope mapping from escape mutants showed that all the seven mAbs could bind to the head region of the N9 NA close to the enzyme activity sites, and four key sites of N9 NA were reported for the first time. The mAbs D3 and 7H2 could simultaneously inhibit the cleavage of the sialic acid of fetuin protein with large molecular weight and NA-XTD with small molecule weight in the NA inhibition experiment, prevent the formation of virus plaque at a low concentration, and effectively protect the mice from the challenge of the lethal dose of H7N9 virus.
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