Lattice Strain and Charge Redistribution of Pt Cluster/Ir Metallene Heterostructure for Ethylene Glycol to Glycolic Acid Conversion Coupled with Hydrogen Production.

Upgrading overall water splitting (OWS) system and developing high-performance electrocatalysts is an attractive way to the improve efficiency and reduce the consumption of hydrogen (H2 ) production from electrolyzed water. Here, a Pt cluster/Ir metallene heterojunction structure (Pt/Ir hetero-metallene) with a unique Pt/Ir interface is reported for the conversion of ethylene glycol (EG) to glycolic acid (GA) coupled with H2 production. With the assistance of ethylene glycol oxidation (EGOR), the Pt/Ir||Pt/Ir hetero-metallene two-electrode water electrolysis system exhibits a lower cell voltage of 0.36 V at 10 mA cm-2 . Furthermore, the Faradaic efficiency of EG to GA is as high as 87%. The excellent performance of this new heterostructure arise from the charge redistribution and strain effects induced by Pt-Ir interactions between the heterogeneous interfaces, as well as the larger specific surface area and more active sites due to the metallene structure.

Tetrahydrobiopterin inhibitor-based antioxidant metabolic strategy for enhanced cancer ferroptosis-immunotherapy.

The induction of immunogenic ferroptosis in cancer cell is limited by the complex and delicate antioxidant system in the organism. Synergistic induction of oxidative damage and inhibition of the defensive redox system in tumor cells is critical to promote lethal accumulation of lipid peroxides and activate immunogenic death (ICD). To address this challenge, we present a multifunctional and dual-responsive layered double hydroxide (LDH) nanosheet to enhance immunogenic ferroptosis. The MTX-LDH@MnO2 nanoplatform is constructed by intercalating methotrexate (MTX) into LDH interlayers and electrostatically absorbing biomineralized ovalbumin (OVA)-MnO2 onto the LDH surface. Specifically, the released Mn2+ from the incorporated MnO2 triggers a Fenton-like reaction, leading to reactive oxygen species (ROS) accumulation, while the depletion of reduced glutathione (GSH) further intensifies oxidative stress, resulting in the induction of ferroptosis. MTX is released in response to the acidic environment of tumor cells and inhibits the regeneration of tetrahydrobiopterin (BH4), modulating the GTP cyclic hydrolase 1 (GCH1)/BH4 axis. MTX disrupts the antioxidant metabolic activity regulated by GCH1/BH4 axis and inhibits ROS consumption, further boosting the ferroptosis effect, which promoted the release of damage-associated molecular patterns (DAMPs) and triggered ICD in the tumor. This activation subsequently leads to significant antitumor immune reactions, including DCs maturation, infiltration of CD4+/CD8+ T cells and cytokines release. The redox-controllable nanoplatform demonstrates promising anticancer efficacy in a mouse breast model providing a novel strategy for cancer immunotherapy.

Prospective, multi-center post-marketing surveillance cohort study to monitor the safety of the human papillomavirus-16/18 AS04-adjuvanted vaccine in Chinese girls and women aged 9 to 45 years, 2018-2020.

Following the approval of Cervarix for the immunization of girls and women in China against high-risk human papillomavirus types 16 and 18, a non-interventional post-authorization safety study was performed. A multi-center prospective cohort study assessed safety following Cervarix vaccination of Chinese girls and women aged 9-45 years between 31 May 2018 and 3 December 2020. Adverse events following immunization (AEFIs), potential immune-mediated diseases (pIMDs), and pregnancy-related outcomes were collected up to 12 months from the third immunization or 24 months from the first immunization, whichever came first. Among 3,013 women who received 8,839 Cervarix doses, 167 (5.5%) reported ≥ 1 any AEFI, and 22 (0.7%) reported 40 serious AEFIs. During the 30 days after each dose, 147 women (4.9%) reported 211 medically attended AEFIs, including 3 serious AEFIs reported by 1 woman (0.03%). One woman reported a pIMD. Cervarix was inadvertently administered to 65 women (2.2%) within 60 days before conception or during pregnancy. Of these women, 34 (52.3%) gave birth to live infant(s) with no apparent congenital anomalies, and 1 (1.5%) woman gave birth to a live infant with a congenital anomaly. No serious AEFIs or pIMDs were considered to be related to the vaccination. In Chinese women aged 9-45 years, immunization with the Cervarix three-dose schedule was well tolerated. Overall, no safety concerns were identified, although rare adverse events may have been missed due to the study sample size.Clinical trial registration: NCT03438006.

Infection with high-risk human papillomavirus is a prerequisite for cervical cancerCervarix is a human papillomavirus-16/18 AS04-adjuvanted vaccineMulti-centre prospective cohort study to monitor safety of Cervarix immunisationSafety was monitored in 3,013 girls/women aged 9­45 years in China (8,839 doses)Cervarix was well tolerated, and no safety concerns were identified.

Safety, immunogenicity, and efficacy of an mRNA COVID-19 vaccine (RQ3013) given as the fourth booster following three doses of inactivated vaccines: a double-blinded, randomised, controlled, phase 3b trial.

Background: Heterologous vaccine schedules have been recommended to provide superior immunity and protection against emergent SARS-CoV-2 variants of concern. We aimed to evaluate the safety, immunogenicity, and efficacy of an mRNA COVID-19 vaccine RQ3013 compared with adenoviral vectored vaccine Ad5-nCoV and protein subunit vaccine ZF2001 as the fourth dose in adults primed with three doses of inactivated vaccines in China. Methods: We conducted a double-blinded, randomised, controlled, phase 3b trial among healthy Chinese adults at Lancang County, Yunnan, China. Adults who had received three doses of inactivated COVID-19 vaccines at least 6 months prior were randomly allocated (3:1:1) to receive heterologous boosters with RQ3013, Ad5-nCoV, or ZF2001. We assessed safety within 28 days post boost and the serum geometric mean titres (GMTs) of neutralising antibodies (NAbs) against the live SARS-CoV-2 omicron variant BA.5 on day 14 post-boost. We used Poisson regression to assess the vaccine efficacy against the first episode of virologically confirmed symptomatic COVID-19 occurring at least 7 days post boost. Subgroup analyses categorized by age and sex were also performed for safety and immunogenicity outcomes. This trial has been registered with the Chinese Clinical Trial Registry (ChiCTR2200065281) and is now complete. Findings: Between December 12 and December 18, 2022, a total of 1382 adults were screened, and 1250 were enrolled and randomly assigned to receive one dose of RQ3013 (n = 750), Ad5-nCoV (n = 250), or ZF2001 (n = 250). Although solicited adverse reactions within 28 days post boost were more frequent in the RQ3013 group (175 [23.3%]) compared to the control groups (24 [9.6%] in both the Ad5-nCOV and ZF2001 groups, P < 0.05), incidences of Grade 3 events were low (9 [0.7%]) and comparable across three groups (P > 0.05). On day 14 post-boost, RQ3013 (GMT 69.14, 95% CI 47.90-99.81) elicited 4.8-fold and 5.6-fold higher concentrations of NAbs against BA.5 than did Ad5-nCoV (14.37, 7.78-26.56) and ZF2001 (12.21, 5.13-29.06), respectively. On day 28 post-boost, RQ3013 demonstrated a relative efficacy of 62.2% (95% CI 13.7-83.1, P = 0.02) compared to Ad5-nCoV, and of 69.0% (33.5-85.7, P = 0.002) compared to ZF2001. Interpretation: The administrations of all the three heterologous boosters were well tolerated. The heterologous prime-boost regimen with RQ3013 elicited superior immune responses and demonstrated better protection against symptomatic SARS-CoV-2 infections compared with Ad5-nCoV or ZF2001, supporting the use of RQ3013 as a booster vaccination in adults. Funding: Yunnan Province Science and Technology Department (grant no.202302AA310047).

Electron Regulation of Heterostructured Pt/Rh Metallene Boosts Ethylene Glycol Electrooxidation and Hydrogen Evolution.

The research on high-efficiency two-dimensional (2D) catalytic materials for the small-molecule oxidation-assisted hydrogen evolution reaction (HER) is prospective for efficient hydrogen production. Herein, we report heterostructured Pt/Rh metallene with Pt nanoparticles (NPs) uniformly anchored on Rh metallene for the HER and ethylene glycol oxidation reaction (EGOR). The ultrathin sheet structure of the Pt/Rh metallene offers high surface areas and sufficient active sites. More importantly, the Pt/Rh heterostructure can optimize catalytic active centers and adjust electronic structure. Thus, Pt/Rh metallene exhibits superior electrocatalytic HER activity with a low overpotential of 28 mV in 1 M KOH at 10 mA cm-2 and EGOR activity with a specific activity of 8.39 mA cm-2 in 1 M KOH with 3 M EG, along with outstanding CO tolerance. In a two-electrode system, Pt/Rh metallene requires a low potential of 0.51 V for stable and efficient hydrogen production at 10 mA cm-2 in 1 M KOH + 3 M EG, with the simultaneous production of high-value-added products. The job proposes an attractive strategy for the synthesis of 0D/2D metallene toward simultaneous energy-saving hydrogen production and chemical update.

SDH mutations, as potential predictor of chemotherapy prognosis in small cell lung cancer patients.

PURPOSE: Small cell lung cancer (SCLC) is an aggressive and rapidly progressive malignant tumor characterized by a poor prognosis. Chemotherapy remains the primary treatment in clinical practice; however, reliable biomarkers for predicting chemotherapy outcomes are scarce. METHODS: In this study, 78 SCLC patients were stratified into "good" or "poor" prognosis cohorts based on their overall survival (OS) following surgery and chemotherapeutic treatment. Next-generation sequencing was employed to analyze the mutation status of 315 tumorigenesis-associated genes in tumor tissues obtained from the patients. The random forest (RF) method, validated by the support vector machine (SVM), was utilized to identify single nucleotide mutations (SNVs) with predictive power. To verify the prognosis effect of SNVs, samples from the cbioportal database were utilized. RESULTS: The SVM and RF methods confirmed that 20 genes positively contributed to prognosis prediction, displaying an area under the validation curve with a value of 0.89. In the corresponding OS analysis, all patients with SDH, STAT3 and PDCD1LG2 mutations were in the poor prognosis cohort (15/15, 100%). Analysis of public databases further confirms that SDH mutations are significantly associated with worse OS. CONCLUSION: Our results provide a potential stratification of chemotherapy prognosis in SCLC patients, and have certain guiding significance for subsequent precise targeted therapy.

Morpholinyl silicon phthalocyanine nanoparticles with lysosome cell death and two-photon imaging functions for in vitro photodynamic therapy of cancer cells.

The lysosome is an important target for realizing antitumor therapy. Lysosomal cell death exerts significant therapeutic effects on apoptosis and drug-resistance. The development of lysosome-targeting nanoparticles to obtain efficient cancer treatment is challenging. In this article, nanoparticles composed of DSPE@M-SiPc and possessing bright two-photon fluorescence, lysosome targeting ability, and photodynamic therapy multifunctionalities are prepared by encapsulating morpholinyl-substituted silicon phthalocyanine (M-SiPc) with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (DSPE). Two photon fluorescence bioimaging showed that M-SiPc and DSPE@M-SiPc mainly locate in lysosomes after cellular internalization. Upon irradiation, DSPE@M-SiPc effectively generates reactive oxygen species and damages the function of lysosome, subsequently leading to lysosomal cell death. DSPE@M-SiPc is a promising photosensitizer for cancer treatment.

Synergistic coupling of IrNi/Ni(OH)2nanosheets with polypyrrole and iron oxyhydroxide layers for efficient electrochemical overall water splitting.

The design of electrocatalysts with excellent activity and stability for overall water splitting is highly desirable, and remains a challenge. Constructing heterojunctions onto the same substrate is beneficial for the integration of a water-splitting reaction. Herein, self-supported IrNi/Ni(OH)2@PPy and IrNi/Ni(OH)2@FeOOH are fabricated by coupling polypyrrole (PPy) and iron oxyhydroxide (FeOOH) on IrNi/Ni(OH)2nanosheets array, respectively. Benefiting from the nanosheet structure, composition, and heterogeneous interface, the as-constructed IrNi/Ni(OH)2@PPy and IrNi/Ni(OH)2@FeOOH catalysts can efficiently drive the hydrogen evolution reaction and oxygen evolution reaction, respectively. Moreover, the electrolyzer consisting of IrNi/Ni(OH)2@PPy and IrNi/Ni(OH)2@FeOOH for water splitting requires only a low cell voltage of 1.49 V to deliver 10 mA cm-2. This study provides a useful strategy for constructing efficient electrocatalysts by synergistic composition modulation and interface engineering.

Highly tough and elastic microspheric gel for transarterial catheter embolization in treatment of liver metastasis tumor.

Transarterial embolization is a widely recognized clinical treatment method for liver tumors. Given that the soft and easily damaged features of embolic particles may limit tumor embolization efficiency, the present study carries out an attempt of fabricating tough and elastic microspheric gel for promoting embolization efficiency. To promote the toughness of hydrogel, poly(ethylene glycol)-co-poly(ε-caprolactone)-co-poly(ethylene glycol) (PPP) and PPP with two terminal double bonds (PPPDA) are co-assembled into nano-micelles, which are connected with methacrylated chitosan (CSMA) to fabricate microspheric gels via microfluidic technology. Lowering double bond density of micelles promotes the freedom degree of micelles, significantly enhancing hydrogel toughness. To compensate for the strength loss caused by the decrease of double bond density of micelles, phytic acid (PA) are employed to interact with CS to form a physical network, further improving hydrogel strength and toughness. The CS-PPPDA&PPP-PA microspheric gels exhibit higher blocking effect in vitro. A rabbit VX2 liver metastasis tumor model is prepared to verify the embolization efficacy of CS-PPPDA&PPP-PA microspheric gels. Compared with clinical used microspheres, fewer CS-PPPDA&PPP-PA microspheric gels can achieve enough embolization efficiency. After embolization for 14 days, CS-PPPDA&PPP-PA microspheric gels exhibit improved tumor necrosis rate and promoted tumor cells apoptosis with reduced inflammation in surrounding tissues, confirming advanced embolic efficiency of tough microgels.

Selective CO2 Electroreduction to Formate on Polypyrrole-Modified Oxygen Vacancy-Rich Bi2 O3 Nanosheet Precatalysts by Local Microenvironment Modulation.

Challenges remain in the development of highly efficient catalysts for selective electrochemical transformation of carbon dioxide (CO2 ) to high-valued hydrocarbons. In this study, oxygen vacancy-rich Bi2 O3 nanosheets coated with polypyrrole (Bi2 O3 @PPy NSs) are designed and synthesized, as precatalysts for selective electrocatalytic CO2 reduction to formate. Systematic material characterization demonstrated that Bi2 O3 @PPy precatalyst can evolve intoBi2 O2 CO3 @PPy nanosheets with rich oxygen vacancies (Bi2 O2 CO3 @PPy NSs) via electrolyte-mediated conversion and function as the real active catalyst for CO2 reduction reaction electrocatalysis. Coating catalyst with a PPy shell can modulate the interfacial microenvironment of active sites, which work in coordination with rich oxygen vacancies in Bi2 O2 CO3 and efficiently mediate directional selective CO2 reduction toward formate formation. With the fine-tuning of interfacial microenvironment, the optimized Bi2 O3 @PPy-2 NSs derived Bi2 O2 CO3 @PPy-2 NSs exhibit a maximum Faradaic efficiency of 95.8% at -0.8 V (versus. reversible hydrogen electrode) for formate production. This work might shed some light on designing advanced catalysts toward selective electrocatalytic CO2 reduction through local microenvironment engineering.

Defect-Rich PdIr Bimetallene Nanoribbons with Interatomic Charge Localization for Isopropanol-Assisted Seawater Splitting.

Metallene with outstanding physicochemical properties is an efficient two-dimensional electrocatalysts for sustainable hydrogen (H2 ) production applications. However, the controllable fabrication of extended atomically thin metallene nanoribbons remains a formidable challenge. Herein, this work proposes a controllable preparation strategy for atomically thin defect-rich PdIr bimetallene nanoribbons (PdIr BNRs) with a thickness of only 1.5 nm for the efficient and stable isopropanol-assisted seawater electrolytic H2 production. When using PdIr BNRs as catalyst to build an isopropanol-assisted seawater electrolysis system, a voltage of only 0.38 V is required at @10 mA cm-2 to achieve energy-saving H2 production, while producing high value-added acetone at the anode. The aberration-corrected high-resolution transmission electron microscopy (HRTEM) clearly reveals that the PdIr BNRs possess abundant structural defects, which can additionally serve as highly catalytically active sites. Density functional theory (DFT) calculations combined with X-ray absorption spectroscopy studies reveal that the introduction of Ir atoms can induce the formation of a localized charge region and shift the d-band center of Pd down, thereby reducing the adsorption energy on the catalyst in favor of the rapid desorption of H2 . This work opens the way for the controllable design and construction of defect-rich atomically thin metallene nanoribbons for efficient electrocatalytic applications.

Staplers versus energy devices for the intersegmental plane separation in thoracoscopic segmentectomy: a comparative study.

BACKGROUND: In segmentectomy, in addition to the anatomy of the segmental hilum, the identification and separation of the intersegmental plane is also an important step of the operation. Because of its simplicity and high efficiency, most thoracic surgeons choose the staplers. But the energy devices also have its unique advantages in the separation of the intersegmental plane. This study compared the clinical efficacy of staplers and energy devices in the separation of the intersegmental planes during the uniport thoracoscopic segmentectomy through the clinical data. METHODS: Clinical data of 89 patients undergoing uniport VATS lung segmentectomy from January 2019 to October 2020 at the First Affiliated Hospital of Soochow University were analyzed retrospectively. According to the different treatment methods of intersegmental plane, the patients were divided into two groups, 55 in the stapler group and 34 in the energy device group. The clinical data of the two groups were compared and analyzed statistically. And the univariate and multivariate logistic regression were also used to explore the influencing factors of postoperative complications. RESULTS: Lung segmentectomy was successfully operated in both groups. There were statistically significant differences in operative duration, number of staplers used, surgical expenses and postoperative complications (P < 0.05). In terms of general data, including tumor location, operative hemorrhage, drainage volume on the first postoperative day, total postoperative drainage volume, postoperative chest tube retention duration, postoperative hospital stay, postoperative blood routine indexes, and postoperative pulmonary function indexes after 3 months, no significant differences were observed (P > 0.05). Smoking history (OR 5.08, 95% CI 1.05-24.56, P = 0.043) and intersegmental plane treatment (OR 3.18, 95% CI 1.11-9.14, P = 0.031) were risk factors for postoperative complications. Patients of the energy device group had a higher incidence of postoperative complications. CONCLUSIONS: In uniport thoracoscopic segmentectomy, the use of energy devices to treat the intersegmental plane will result in longer operative duration and higher postoperative complication rate, but it does not affect postoperative recovery and can help reduce surgical expenses. Both methods are safe and reliable. Clinically, the two methods can be reasonably selected according to the specific situation.

Rh metallene with functionalized polypyrrole surface for hydrogen evolution over a wide pH range.

Interface engineering of two-dimensional (2D) materials by conductive polymer modification is one of the valid methods to promote hydrogen evolution reaction (HER) performance. Herein, we report a simple and universal strategy for the synthesis of polypyrrole (PPy) modified Rh metallene (Rh@PPy metallene) towards an efficient pH-universal HER. Due to the unique ultrathin 2D metallene structure and the optimized electronic structure between the metallene-PPy surfaces, the as-prepared Rh@PPy metallene not only exhibits excellent HER activity with low overpotentials of 16, 39 and 42 mV in 0.5 M H2SO4, 1 M KOH, and 1 M phosphate buffer solution at current density of 10 mA cm-2, but also displays outstanding stability and durability. This work provides a well-founded pathway to constructe metallene-organic interfaces for various electrocatalytic applications.

Heterogeneous Pd-PdO mesoporous film for ammonia electrosynthesis.

Exploring cost-effective and highly active electrocatalysts is of great significance for sustainable electrochemical NH3synthesis. Palladium (Pd)-based catalysts have been unanimously considered as one of the most efficient catalysts for the nitrogen reduction reaction (NRR). Herein, self-supported mesoporous Pd film with partial oxidation on Ni foam (mPd-PdO/NF) was synthesized through the micelle-assisted chemical replacement method coupled with air oxidation under 260 °C, and the mPd-PdO/NF electrocatalyst exhibited superior NRR performance with the maximum values ofrNH3(24.8 mg h-1mgcat.-1) and FE (16.64%) were obtained at -0.1 V, relative to the single counterparts (mPd/NF and mPdO/NF). It is proposed that both metallic Pd and its oxide domains when co-existing with a phase boundary between them can facilitate nitrogen activation and hydrogenation, resulting in an enhanced NRR performance. This work provides an inspiring strategy for the rational design of highly active and durable metal-metal-oxide nanoarchitectonics for ammonia electrosynthesis.

Quercetin Inhibits Tumorigenesis of Colorectal Cancer Through Downregulation of hsa_circ_0006990.

Quercetin can significantly inhibit the progression of colorectal cancer (CRC). However, its specific mechanism remains largely unclear. In this study, we aimed to explore the correlation among quercetin, tumour-associated macrophages (TAMs) and circular RNAs (circRNAs) in the progression of CRC and to present a novel strategy for the treatment of CRC. In this study, we revealed that quercetin could suppress the autophagy of M2-TAMs and induced their differentiation into M1-TAMs, by which quercetin significantly reversed the inhibition of M2-TAMS on CRC cell apoptosis and the promotion of M2-TAMS on CRC cell proliferation. Moreover, quercetin could promote the expression of downregulated hsa_circ_0006990 in CRC cells co-cultured with M2-TAMs, and the overexpression of hsa_circ_0006990 significantly reversed the anti-tumour effect of quercetin on CRC. Furthermore, we found quercetin can notably suppress the progression of CRC via mediation of the hsa_circ_0006990/miR-132-3p/MUC13 axis. In conclusion, our results suggested that quercetin inhibits the tumorigenesis of CRC via inhibiting the polarisation of M2 macrophages and downregulating hsa_circ_0006990. Our study provides useful insights for those exploring new methods of treating CRC.

Maternal obesity induces liver lipid accumulation of offspring through the lncRNA Lockd/mTOR autophagy pathway.

Maternal obesity increases the risk of obesity and metabolic diseases in the offspring in early life, but the underlying mechanism has not been elucidated. The aim of this study is to explore whether lncRNA and autophagy are involved in the regulation of maternal obesity on the liver lipid metabolism of the offspring. C57BL/6 mice were fed high-fat diet (HFD) or standard chow diet (CD) for 12 weeks before the start of mating and continued until the end of the lactation period. The lipid metabolism indexes of the three-week-old offspring were detected. The RNA sequencing (RNA-seq) and western blot analysis for autophagy-related protein were performed on the offspring's liver to determine the comprehensive expression profile of lncRNA and autophagy level. In addition, AML12 cells were treated with small interfering RNA (siRNA) and rapamycin. Western blot, qRT-PCR and Oil Red O staining were used to detect protein expression, mRNA expression and lipid accumulation levels. As a result, maternal obesity leads to low expression of lncRNA Lockd and autophagy inhibition in the offspring's liver. Knockdown of lncRNA Lockd could further inhibit autophagy and aggravate lipid accumulation. Rapamycin treatment could improve lipid accumulation in AML12 cells. Our study revealed that maternal obesity caused low expression of lncRNA Lockd in the offspring's liver, and lncRNA Lockd positively regulates autophagy through the mTOR signaling pathway. This study provides new insights into the occurrence of lipid accumulation in the liver of offspring.

Global diversity of policy, coverage, and demand of COVID-19 vaccines: a descriptive study.

BACKGROUND: Hundreds of millions of doses of coronavirus disease 2019 (COVID-19) vaccines have been administered globally, but progress on vaccination varies considerably between countries. We aimed to provide an overall picture of COVID-19 vaccination campaigns, including policy, coverage, and demand of COVID-19 vaccines. METHODS: We conducted a descriptive study of vaccination policy and doses administered data obtained from multiple public sources as of 8 February 2022. We used these data to develop coverage indicators and explore associations of vaccine coverage with socioeconomic and healthcare-related factors. We estimated vaccine demand as numbers of doses required to complete vaccination of countries' target populations according to their national immunization program policies. RESULTS: Messenger RNA and adenovirus vectored vaccines were the most commonly used COVID-19 vaccines in high-income countries, while adenovirus vectored vaccines were the most widely used vaccines worldwide (180 countries). One hundred ninety-two countries have authorized vaccines for the general public, with 40.1% (77/192) targeting individuals over 12 years and 32.3% (62/192) targeting those ≥ 5 years. Forty-eight and 151 countries have started additional-dose and booster-dose vaccination programs, respectively. Globally, there have been 162.1 doses administered per 100 individuals in target populations, with marked inter-region and inter-country heterogeneity. Completed vaccination series coverage ranged from 0.1% to more than 95.0% of country target populations, and numbers of doses administered per 100 individuals in target populations ranged from 0.2 to 308.6. Doses administered per 100 individuals in whole populations correlated with healthcare access and quality index (R2 = 0.59), socio-demographic index (R2 = 0.52), and gross domestic product per capita (R2 = 0.61). At least 6.4 billion doses will be required to complete interim vaccination programs-3.3 billion for primary immunization and 3.1 billion for additional/booster programs. Globally, 0.53 and 0.74 doses per individual in target populations are needed for primary immunization and additional/booster dose programs, respectively. CONCLUSIONS: There is wide country-level disparity and inequity in COVID-19 vaccines rollout, suggesting large gaps in immunity, especially in low-income countries.

FAT1 and MSH2 Are Predictive Prognostic Markers for Chinese Osteosarcoma Patients Following Chemotherapeutic Treatment.

Osteosarcoma is characterized by diverse genetic mutations, including single-nucleotide variants (SNVs), which can complicate clinical outcomes of the treatment. This study identified key mutations or polymorphisms in genes that correlate with osteosarcoma prognoses. A total of 110 patients with osteosarcoma were assigned to "good" or "poor" cohorts depending on their 5-year disease-free survival (DFS) after surgery and chemotherapeutic treatment. We performed next-generation sequencing analysis of tumor tissues for prognosis-associated SNVs in 315 tumorigenesis-related genes, followed by modeling of clinical outcomes for these patients using random forest classification via a support vector machine (SVM). Data from the Chinese Millionome Database were used to compare SNV frequency in osteosarcoma patients and healthy people. SVM screening identified 17 nonsynonymous SNVs located in 15 genes, of which rs17224367 and rs3733406 (located in MSH2 and FAT1, respectively) were strongly correlated with osteosarcoma prognosis. These results were verified in a 26-patient validation cohort, confirming that these SNVs could be used to predict prognosis. These results demonstrated that two SNVs located in MSH2 and FAT1 are associated with prognosis of osteosarcoma patients. © 2022 American Society for Bone and Mineral Research (ASBMR).

Model-based evaluation of alternative reactive class closure strategies against COVID-19.

There are contrasting results concerning the effect of reactive school closure on SARS-CoV-2 transmission. To shed light on this controversy, we developed a data-driven computational model of SARS-CoV-2 transmission. We found that by reactively closing classes based on syndromic surveillance, SARS-CoV-2 infections are reduced by no more than 17.3% (95%CI: 8.0-26.8%), due to the low probability of timely identification of infections in the young population. We thus investigated an alternative triggering mechanism based on repeated screening of students using antigen tests. Depending on the contribution of schools to transmission, this strategy can greatly reduce COVID-19 burden even when school contribution to transmission and immunity in the population is low. Moving forward, the adoption of antigen-based screenings in schools could be instrumental to limit COVID-19 burden while vaccines continue to be rolled out.

A Germline Variant at 8q24 Contributes to the Serum p2PSA Level in a Chinese Prostate Biopsy Cohort.

INTRODUCTION: The clinical performance of [-2]proPSA (p2PSA) and its derivatives in predicting the presence and aggressiveness of prostate cancer (PCa) has been well evaluated in prostate biopsy patients. However, no study has been performed to evaluate the common genetic determinants that affect serum level of p2PSA. MATERIALS AND METHODS: Here, we performed a two-stage genome-wide association study (GWAS) on the p2PSA level in Chinese men who underwent a transperineal ultrasound-guided prostate biopsy at Huashan Hospital, Shanghai Cancer Center, and Ruijin Hospital in Shanghai, China. Germline variants significantly associated with the p2PSA level in the first stage (n = 886) were replicated in the second stage (n = 1,128). Multivariate linear regression was used to assess the independent contribution of confirmed single nucleotide polymorphisms (SNPs) and known covariates, such as age, to the level of p2PSA. RESULTS: A novel non-synonymous SNP, rs72725879, in region 8q24.21 of the PRNCR1 gene was significantly associated with the serum level of p2PSA in this two-stage GWAS (p = 2.28 × 10-9). Participants with homozygous "T" alleles at rs72725879 had higher p2PSA levels compared to allele "C" carriers. This variant was also nominally associated with PCa risk (p-combined = 3.44 × 10-18). The association with serum level of p2PSA was still significant after adjusting for PCa risk and age (p = 0.017). CONCLUSIONS: Our study shows that the genetic variants in the 8q24.21 region are associated with the serum level of p2PSA in a large-scale Chinese population. By taking inherited variations between individuals into account, the findings of these genetic variants may help improve the performance of p2PSA in predicting prostate cancer.