ABSTRACT
Chinese diesel trucks are the main contributors to NOx and particulate matter (PM) vehicle emissions. An increase in diesel trucks could aggravate air pollution and damage human health. The Chinese government has recently implemented a series of emission control technologies and measures for air quality improvement. This paper summarizes recent control technologies and measures for diesel truck emissions in China and introduces the comprehensive application of control technologies and measures in Beijing-Tianjin-Hebei and surrounding regions. Remote online monitoring technology has been adopted according to the China VI standard for heavy-duty diesel trucks, and control measures such as transportation structure adjustment and heavy pollution enterprise classification control continue to support the battle action plan for pollution control. Perspectives and suggestions are provided for promoting pollution control and supervision of diesel truck emissions: adhere to the concept of overall management and control, vigorously promote the application of systematic and technological means in emission monitoring, continuously facilitate cargo transportation structure adjustment and promote new energy freight vehicles. This paper aims to accelerate the implementation of control technologies and measures throughout China. China is endeavouring to control diesel truck exhaust pollution. China is willing to cooperate with the world to protect the global ecological environment.
Subject(s)
Air Pollutants , Air Pollution , Environmental Monitoring , Particulate Matter , Vehicle Emissions , Vehicle Emissions/analysis , China , Air Pollutants/analysis , Air Pollution/prevention & control , Air Pollution/statistics & numerical data , Environmental Monitoring/methods , Particulate Matter/analysis , Motor VehiclesABSTRACT
To evaluate the measurement accuracy of horizontal and vertical remote emission sensing (RES) equipment, a real-world dynamic test was carried out in Chengdu by using electric vehicles equipped with various concentrations of standard gases. In addition, a new vertical remote sensing spectral data algorithm based on image processing (ISPA) was developed to improve the measurement capability. The results showed that the ISPA provided a greater percentage of valid data and lower relative errors; thus, our new algorithm could more effectively analyze the spectral data to measure vehicle emission levels. The percentages of valid horizontal and vertical RES data were 71% and 84%, respectively. The mean relative errors of CO2, CO, HC and NO measured by the vertical RES were about 5%, 20%, 20% and 40%, respectively, and those of CO2, CO and NO measured by the horizontal RES were 3%, 13% and 15%, respectively. For the common vehicle emission concentration, the percentage of valid data for the two RES types increased with increasing gas concentration. As the vehicle speed increased, the relative errors of the horizontal RES equipment showed an increasing trend for the same concentration of gas. Furthermore, for the same speed segment, the relative errors of the horizontal RES equipment increased as the simulated emission concentration decreased. The vertical RES equipment did not exhibit a consistent trend in terms of changes. This study provides a data quality reference for further RES applications.
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The development of necroptosis inhibitors has emerged as a promising strategy to effectively mitigate necroptosis-related inflammatory diseases, neurodegenerative diseases, and cancers. In this paper, we reported a series of 6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazole derivatives as potent necroptosis inhibitors. The representative compound 26 displayed potent anti-necroptotic activity in both human and mouse cellular assays and exhibited potent inhibitory activity against receptor-interacting protein kinase 1 (RIPK1). In vivo pharmacokinetic studies were performed to determine the oral exposure of compound 26. Finally, molecular docking elucidated that compound 26 could effectively bind to the allosteric pocket of RIPK1 and serve as a type III inhibitor. Taken together, our findings highlighted that compound 26 represented a promising lead compound for future necroptosis inhibitor development.
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Metal halide perovskites (MHPs) have emerged as attractive candidates for producing green hydrogen via photocatalytic pathway. However, the presence of abundant defects and absence of efficient hydrogen evolution reaction (HER) active sites on MHPs seriously limit the solar-to-chemical (STC) conversion efficiency. Herein, to address this issue, we present a bi-functionalization strategy through decorating MHPs with a molecular molybdenum-sulfur-containing co-catalyst precursor. By virtue of the strong chemical interaction between lead and sulfur and the good dispersion of the molecular co-catalyst precursor in the deposition solution, a uniform and intimate decoration of the MHPs surface with lead sulfide (PbS) and amorphous molybdenum sulfide (MoSx) co-catalysts is obtained simultaneously. We show that the PbS co-catalyst can effectively passivate the Pb-related defects on the MHPs surface, thus retarding the charge recombination and promoting the charge transfer efficiency significantly. The amorphous MoSx co-catalyst further promotes the extraction of photogenerated electrons from MHPs and facilitates the HER catalysis. Consequently, drastically enhanced photocatalytic HER activities are obtained on representative MHPs through the synergistic functionalization of PbS and MoSx co-catalysts. A solar-to-chemical (STC) conversion efficiency of ca. 4.63% is achieved on the bi-functionalized FAPbBr3-xIx, which is among the highest values reported for MHPs.
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Necroptosis is a form of regulated necrotic cell death and has been confirmed to play pivotal roles in the pathogenesis of multiple autoimmune diseases such as rheumatoid arthritis (RA) and psoriasis. The development of necroptosis inhibitors may offer a promising therapeutic strategy for the treatment of these autoimmune diseases. Herein, starting from the in-house hit compound 1, we systematically performed structural optimization to discover potent necroptosis inhibitors with good pharmacokinetic profiles. The resulting compound 33 was a potent necroptosis inhibitor for both human I2.1 cells (IC50 < 0.2 nM) and murine Hepa1-6 cells (IC50 < 5 nM). Further target identification revealed that compound 33 was an inhibitor of receptor interacting protein kinase 1 (RIPK1) with favorable selectivity. In addition, compound 33 also exhibited favorable pharmacokinetic profiles (T1/2 = 1.32 h, AUC = 1157 ng·h/mL) in Sprague-Dawley rats. Molecular docking and molecular dynamics simulations confirmed that compound 33 could bind to RIPK1 with high affinity. In silico ADMET analysis demonstrated that compound 33 possesses good drug-likeness profiles. Collectively, compound 33 is a promising candidate for antinecroptotic drug discovery.
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BACKGROUND: Whether programmed cell death-1/ligand-1 (PD-1/PD-L1) blockade-based neoadjuvant treatment may benefit locally advanced oncogene-mutant non-small cell lung cancer (NSCLC) patients remains controversial. This retrospective study was designed to observe the efficacy and safety of neoadjuvant PD-1/PD-L1 blockade plus chemotherapy versus chemotherapy and corresponding tyrosine kinase inhibitors (TKIs) in patients with resectable oncogene-positive NSCLC. METHODS: Patients with potential resectable NSCLC harbouring oncogene alterations who had received neoadjuvant treatment were retrospectively recruited, and an oncogene-negative cohort of patients who received neoadjuvant PD-(L)1 blockade-based neoadjuvant treatment was reviewed for comparison during the same period. The primary aim was to observe the treatment efficacy and event-free survival (EFS) of these agents. Safety profile, molecular target, and immunologic factor data, including PD-L1 expression and tumour mutational burden (TMB), were also obtained. RESULTS: A total of 46 patients were recruited. Thirty-one of them harboured oncogene alterations, including EGFR, KRAS, ERBB2, ROS1, MET, RET, ALK, and FGFR3 alterations. Among the oncogene-positive patients, 18 patients received neoadjuvant PD-(L)1 blockade immunotherapy plus chemotherapy (oncogene-positive IO group), 13 patients were treated with neoadjuvant chemotherapy and/or corresponding TKIs or TKIs alone (oncogene-positive chemo/TKIs group), and the other 15 patients were oncogene negative and received neoadjuvant PD-(L)1 blockade plus chemotherapy (oncogene-negative IO group). The pathological complete response (pCR) and major pathological response (MPR) rates were 22.2% (4 of 18) and 44.4% (8 of 18) in the oncogene-positive IO group, 0% (P = 0.120) and 23.1% (3 of 13) (P = 0.276) in the oncogene-positive chemo/TKIs group, and 46.7% (7 of 15) (P = 0.163) and 80.0% (12 of 15) (P = 0.072) in the oncogene-negative IO group, respectively. By the last follow-up, the median EFS time had not reached in the oncogene-positive IO group, and was 29.5 months in the oncogene-positive chemo/TKIs group and 38.4 months in the oncogene-negative IO group. CONCLUSION: Compared with chemotherapy/TKIs treatment, neoadjuvant treatment with PD-(L)1 blockade plus platinum-based chemotherapy was associated with higher pCR/MPR rates in patients with partially resectable oncogene-mutant NSCLC, while the pCR/MPR rates were lower than their oncogene-negative counterparts treated with PD-(L)1 blockade-based treatment. Specifically, oncogene alteration types and other predictors of response to immunotherapy should be taken into account in clinical practice.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , B7-H1 Antigen , Carcinoma, Non-Small-Cell Lung , Immune Checkpoint Inhibitors , Lung Neoplasms , Neoadjuvant Therapy , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/genetics , Female , Male , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Middle Aged , Neoadjuvant Therapy/methods , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Aged , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/metabolism , Immune Checkpoint Inhibitors/therapeutic use , Follow-Up Studies , Survival Rate , Adult , Prognosis , Oncogenes/genetics , Protein Kinase Inhibitors/therapeutic use , Mutation , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/metabolismABSTRACT
One challenge of the structural design of a fluorescent probe is how to improve the detection performance on trace target analytes in complex samples. Herein a new polymer fluorescent nanoprobe (2DSP-C28) has been synthesized, by adopting a two-dimensional (2D), spiropyran (SP)-based nanosheet structure with hydrophobic long-chain alkanes (C28). Unlike a traditional SP-based small molecule probe, the 2DSP-C28probe can exhibit quantitative-fluorescent and photochromic properties. Under the detection of metal-ions, the nanoprobe in dimethyl sulfoxide aqueous solution is selectively fluorescent-quenched-responsive for Fe-ions (â¼100µM), with a characteristic stoichiometric ratio of <10, a high sensitivity (limit of detection: â¼0.2µM). When the nanoprobe is incorporated into electrospun polyethylene oxide, it can be used for gas detection, and display a color-change with acid-base gas and identify the HF gas. It is expected that this new polymer fluorescent nanoprobe can be promisingly applied for rapidly environmental monitoring on the ion or gas pollution.
ABSTRACT
Stimulator of interferon gene (STING) plays critical roles in the cytoplasmic DNA-sensing pathway and in the induction of inflammatory response. Aberrant cytoplasmic DNA accumulation and STING activation are implicated in numerous inflammatory and autoimmune diseases. Here, we reported the discovery of a series of thiazolecarboxamide-based STING inhibitors through a molecular planarity/symmetry disruption strategy. The privileged compound 15b significantly inhibited STING signaling and suppressed immune-inflammatory cytokine levels in both human and murine cells. In vivo experiments demonstrated 15b effectively ameliorated immune-inflammatory cytokines upregulation in MSA-2-stimulated and Trex1-D18N mice. Furthermore, compound 15b exhibited enhanced efficacy in suppressing interferon-stimulated gene 15 (ISG15), a critical positive feedback regulator of STING. Overall, compound 15b deserves further development for the treatment of STING-associated inflammatory and autoimmune diseases.
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In recent years, there has been an increasing amount of research on nitrogen oxides (NOx) emissions, and the environmental impact of aviation NOx emissions at cruising altitudes has received widespread attention. NOx may play a crucial role in altering the composition of the atmosphere, particularly regarding ozone formation in the upper troposphere. At present, the ground emission database based on the landing and takeoff (LTO) cycle is more comprehensive, while high-altitude emission data is scarce due to the prohibitively high cost and the inevitable measurement uncertainty associated with in-flight sampling. Therefore, it is necessary to establish a comprehensive NOx emission database for the entire flight envelope, encompassing both ground and cruise phases. This will enable a thorough assessment of the impact of aviation NOx emissions on climate and air quality. In this study, a prediction model has been developed via convolutional neural network (CNN) technology. This model can predict the ground and cruise NOx emission index for turbofan engines and mixed turbofan engines fueled by either conventional aviation kerosene or sustainable aviation fuels (SAFs). The model utilizes data from the engine emission database (EEDB) released by the International Civil Aviation Organization (ICAO) and results obtained from several in-situ emission measurements conducted during ground and cruise phases. The model has been validated by comparing measured and predicted data, and the results demonstrate its high prediction accuracy for both the ground (R2 > 0.95) and cruise phases (R2 > 0.9). This surpasses traditional prediction models that rely on fuel flow rate, such as the Boeing Fuel Flow Method 2 (BFFM2). Furthermore, the model can predict NOx emissions from aircrafts burning SAFs with satisfactory accuracy, facilitating the development of a more complete and accurate aviation NOx emission inventory, which can serve as a basis for aviation environmental and climatic research. SYNOPSIS: The utilization of the ANOEPM-CNN offers a foundation for establishing more precise emission inventories, thereby reducing inaccuracies in assessing the impact of aviation NOx emissions on climate and air quality.
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Metal-organic frameworks (MOFs) have emerged as promising platforms for photocatalytic hydrogen evolution reaction (HER) due to their fascinating physiochemical properties. Rationally engineering the compositions and structures of MOFs can provide abundant opportunities for their optimization. In recent years, high-entropy materials (HEMs) have demonstrated great potential in the energy and environment fields. However, there is still no report on the development of high-entropy MOFs (HE-MOFs) for photocatalytic HER in aqueous solution. Herein, the authors report the synthesis of a novel p-type HE-MOFs single crystal (HE-MOF-SC) and the corresponding HE-MOFs nanosheets (HE-MOF-NS) capable of realizing visible-light-driven photocatalytic HER. Both HE-MOF-SC and HE-MOF-NS exhibit higher photocatalytic HER activity than all the single-metal MOFs, which are supposed to be ascribed to the interplay between the different metal nodes in the HE-MOFs that enables more efficient charge transfer. Moreover, impressively, the HE-MOF-NS demonstrates much higher photocatalytic activity than the HE-MOF-SC due to its thin thickness and enhanced surface area. At optimum conditions, the rate of H2 evolution on the HE-MOF-NS is ≈13.24 mmol h-1 g-1, which is among the highest values reported for water-stable MOF photocatalysts. This work highlights the importance of developing advanced high-entropy materials toward enhanced photocatalysis.
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Hematopoietic progenitor kinase 1 (HPK1) is a key negative regulator of T-cell receptor (TCR) signaling and a promising target for cancer immunotherapy. The development of novel HPK1 inhibitors is challenging yet promising. In this study, we used a combination of machine learning (ML)-based virtual screening and free energy perturbation (FEP) calculations to identify novel HPK1 inhibitors. ML-based screening yielded 10 potent HPK1 inhibitors (IC50 < 1 µM). The FEP-guided modification of the in-house false-positive hit, DW21302, revealed that a single key atom change could trigger activity cliffs. The resulting DW21302-A was a potent HPK1 inhibitor (IC50 = 2.1 nM) and potently inhibited cellular HPK1 signaling and enhanced T-cell function. Molecular dynamics (MD) simulations and ADME predictions confirmed DW21302-A as candidate compound. This study provides new strategies and chemical scaffolds for HPK1 inhibitor development.Communicated by Ramaswamy H. Sarma.
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The receptor tyrosine kinase AXL has emerged as an attractive target in anticancer drug discovery. Herein, we described the discovery of a new series of 1,6-naphthyridin-4-one derivatives as potent AXL inhibitors. Starting from a low in vivo potency compound 9 which was previously reported by our group, we utilized structure-based drug design and scaffold hopping strategies to discover potent AXL inhibitors. The privileged compound 13c was a highly potent and orally bioavailable AXL inhibitor with an IC50 value of 3.2 ± 0.3 nM. Compound 13c exhibited significantly improved in vivo antitumor efficacy in AXL-driven tumor xenograft mice, causing tumor regression at well-tolerated dose, and demonstrated favorable pharmacokinetic properties (MRT = 16.5 h, AUC0-∞ = 59,815 ng h/mL) in Sprague-Dawley rats. These results suggest that 13c is a promising therapeutic candidate for AXL-targeting cancer treatment.
Subject(s)
Axl Receptor Tyrosine Kinase , Neoplasms , Rats , Humans , Mice , Animals , Proto-Oncogene Proteins , Rats, Sprague-Dawley , Receptor Protein-Tyrosine Kinases , Protein Kinase Inhibitors/pharmacokinetics , Cell Line, Tumor , Cell ProliferationABSTRACT
The photocuring technology based on thiol-ene click reaction can be easily applied for copolymerizing or crosslinking the acrylate monomers for ionogels. However, there is still a problem: when the acrylate monomers contain the popular spiropyran as the stimuli-responsive group, it should be concerned about the participation of the active CîC bond from the ring-opened spiropyran during a thiol-ene reaction, which may in turn affect the stimuli-responsiveness of the spiropyran. Up to now, the structure and properties of spiropyran-containing ionogels in this case have still not been well investigated. Therefore, in this work we carefully study a new spiropyran-containing polyurethane ionogel by crosslinking an acrylate-terminated, spiropyran-containing polyurethane prepolymer and a polythiol in ionic liquid through thiol-ene chemistry. It is found for the first time that, during constructing an ionogel, the coexistence of a reversible thiol-ene reaction between the CîC bond from the ring-opened spiropyran and the thiol group can bring about a different reverse photochromic behavior. The proposed mechanism of the abnormal photochromism is analyzed. In addition, it is also observed that the thiol-ene chemistry can incorporate photomechanical and photoconductive properties into the new spiropyran-containing ionogel.
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Ammonia emissions from motor vehicles have great effect on air pollution and human health in urban areas. Recently, many countries have focus on ammonia emission measurement and control technologies for light-duty gasoline vehicles (LDGVs). To analyze ammonia emission characteristics, three conventional LDGVs and one hybrid electric light-duty vehicle (HEV) were evaluated over different driving cycles. The average ammonia emission factor at 23â was 4.5 ± 1.6 mg/km over Worldwide harmonized light vehicles test cycle (WLTC). Most ammonia emissions mainly concentrated in low and medium speed sections at cold-start stage, which were related to rich burn conditions. The increasing ambient temperatures led to the decrease of ammonia emissions, but high load caused by extremely elevated ambient temperature led to obvious ammonia emissions. The ammonia formation is also related to three-way catalytic converter (TWC) temperatures, and underfloor TWC catalyst could eliminate ammonia partly. The ammonia emission from HEV, which are significant less than LDGV, corresponded to the engine working state. The large temperature difference in the catalysts caused by power source shifts were the main reason. Exploring the effects of various factors on the ammonia emission is beneficial for revealing the instinct formation conditions, providing theoretical support for the future regulations.
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Resonance-enhanced emission (REE) effect was discovered and lead to a novel dye family of hydrostyryl pyridinium derivatives in our recent work. Herein, the REE effect was employed to design a red and near-infrared dual-state emissive fluorophore family of SW-OH-NO2 derivatives which were easily synthesized by coupling an electron-withdrawing group (W) onto nitro(hydroxyl)styryl (S-OH-NO2 ) through a C=C double bond as π-bridge. The deprotonation of a phenolic hydroxyl group promoted by a nitro group and the electron-withdrawing group (W) on the other side of the π-bridge triggered resonance, resulting in significantly red-shifted emission. All the resultant SW-OH-NO2 compounds showed excellent dual-state emission behavior. Remarkably, hydrostyryl quinolinium (SQ-OH-NO2 ) is one of the smallest NIR emitter molecular skeleton (λem =725â nm, MW<400) and showed dual-state emission characteristics and obvious viscosity-depended fluorescent behaviors. In addition to constructing electron donor-acceptor structures and prolonging π-bridges, the REE effect promises a reliable strategy toward novel fluorophores with small size, long emissive wavelength, and dual-emission characteristics, and importantly, feasible industrial manufactures and applications due to their easy and low-cost synthesis strategy.
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Ruthenium (Ru) has been considered a promising electrocatalyst for electrochemical hydrogen evolution reaction (HER) while its performance is limited due to the problems of particle aggregation and competitive adsorption of the reaction intermediates. Herein, we reported the synthesis of a zinc (Zn) modified Ru nanocluster electrocatalyst anchored on multiwalled carbon nanotubes (Ru-Zn/MWCNTs). The Ru-Zn catalysts were found to be highly dispersed on the MWCNTs substrate. Moreover, the Ru-Zn/MWCNTs exhibited low overpotentials of 26 and 119 mV for achieving current intensities of 10 and 100 mA cm-2 under alkaline conditions, respectively, surpassing Ru/MWCNTs with the same Ru loading and the commercial 5 wt% Pt/C (47 and 270 mV). Moreover, the Ru-Zn/MWCNTs showed greatly enhanced stability compared to Ru/MWCNTs with no significant decay after 10,000 cycles of CV sweeps and long-term operation for 90 h. The incorporation of Zn species was found to modify the electronic structure of the Ru active species and thus modulate the adsorption energy of the Had and OHad intermediates, which could be the main reason for the enhanced HER performance. This study provides a strategy to develop efficient and stable electrocatalysts towards the clean energy conversion field.
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In recent years, great efforts have been devoted to reducing emissions from mobile sources with the dramatic growth of motor vehicle and nonroad mobile source populations. Compilation of a mobile source emission inventory is conducive to the analysis of pollution emission characteristics and the formulation of emission reduction policies. This study summarizes the latest compilation approaches and data acquisition methods for mobile source emission inventories. For motor vehicles, a high-resolution emission inventory can be developed based on a bottom-up approach with a refined traffic flow model and real-world speed-coupled emission factors. The top-down approach has advantages when dealing with macroscale vehicle emission estimation without substantial traffic flow infrastructure. For nonroad mobile sources, nonroad machinery, inland river ships, locomotives, and civil aviation aircraft, a top-down approach based on fuel consumption or power is adopted. For ocean-going ships, a bottom-up approach based on automatic identification system (AIS) data is adopted. Three typical cases are studied, including emission reduction potential, a cost-benefit model, and marine shipping emission control. Outlooks and suggestions are given on future research directions for emission inventories for mobile sources: building localized emission models and factor databases, improving the dynamic updating capability of emission inventories, establishing a database of emission factors of unconventional pollutants and greenhouse gas from mobile sources, and establishing an urban high temporal-spatial resolution volatile organic compound (VOC) evaporation emission inventory.
Subject(s)
Air Pollutants , Volatile Organic Compounds , Air Pollutants/analysis , Environmental Monitoring/methods , Vehicle Emissions/analysis , Volatile Organic Compounds/analysis , ShipsABSTRACT
It is critical to determine the real-world performance of vaccines against coronavirus disease 2019 (COVID-19) so that appropriate treatments and policies can be implemented. There was a rapid wave of infections by the Omicron variant in Jilin Province (China) during spring 2022. We examined the effectiveness of inactivated vaccines against Omicron using real-world data from this epidemic. This retrospective case-case study of vaccine effectiveness (VE) examined infected patients who were quarantined and treated from April 16 to June 8, 2022 and responded to an electronic questionnaire. Data were analyzed by univariable and multivariable analyses. A total of 2968 cases with SARS-CoV-2 infections (asymptomatic: 1061, mild disease: 1763, pneumonia: 126, severe disease: 18) were enrolled in the study. Multivariable regression indicated that the risk for pneumonia or severe disease was greater in those who were older or had underlying diseases, but was less in those who received COVID-19 vaccines. Relative to no vaccination, VE against the composite of pneumonia and severe disease was significant for those who received 2 doses (60.1%, 95%CI: 40.0%, 73.5%) or 3 doses (68.1%, 95%CI: 44.6%, 81.7%), and VE was similar in the subgroups of males and females. However, VE against the composite of all three classes of symptomatic diseases was not significant overall, nor after stratification by sex. There was no statistical difference in the VE of vaccines from different manufacturers. The inactivated COVID-19 vaccines protected patients against pneumonia and severe disease from Omicron infection, and booster vaccination enhanced this effect.