Effects of Kv1.3 knockout on pyramidal neuron excitability and synaptic plasticity in piriform cortex of mice.

Kv1.3 belongs to the voltage-gated potassium (Kv) channel family, which is widely expressed in the central nervous system and associated with a variety of neuropsychiatric disorders. Kv1.3 is highly expressed in the olfactory bulb and piriform cortex and involved in the process of odor perception and nutrient metabolism in animals. Previous studies have explored the function of Kv1.3 in olfactory bulb, while the role of Kv1.3 in piriform cortex was less known. In this study, we investigated the neuronal changes of piriform cortex and feeding behavior after smell stimulation, thus revealing a link between the olfactory sensation and body weight in Kv1.3 KO mice. Coronal slices including the anterior piriform cortex were prepared, whole-cell recording and Ca2+ imaging of pyramidal neurons were conducted. We showed that the firing frequency evoked by depolarization pulses and Ca2+ influx evoked by high K+ solution were significantly increased in pyramidal neurons of Kv1.3 knockout (KO) mice compared to WT mice. Western blotting and immunofluorescence analyses revealed that the downstream signaling molecules CaMKII and PKCα were activated in piriform cortex of Kv1.3 KO mice. Pyramidal neurons in Kv1.3 KO mice exhibited significantly reduced paired-pulse ratio and increased presynaptic Cav2.1 expression, proving that the presynaptic vesicle release might be elevated by Ca2+ influx. Using Golgi staining, we found significantly increased dendritic spine density of pyramidal neurons in Kv1.3 KO mice, supporting the stronger postsynaptic responses in these neurons. In olfactory recognition and feeding behavior tests, we showed that Kv1.3 conditional knockout or cannula injection of 5-(4-phenoxybutoxy) psoralen, a Kv1.3 channel blocker, in piriform cortex both elevated the olfactory recognition index and altered the feeding behavior in mice. In summary, Kv1.3 is a key molecule in regulating neuronal activity of the piriform cortex, which may lay a foundation for the treatment of diseases related to piriform cortex and olfactory detection.

Multi-model analysis of gallbladder cancer reveals the role of OxLDL-absorbing neutrophils in promoting liver invasion.

BACKGROUND: Gallbladder cancer (GBC) is the most common and lethal malignancy of the biliary tract that lacks effective therapy. In many GBC cases, infiltration into adjacent organs or distant metastasis happened long before the diagnosis, especially the direct liver invasion, which is the most common and unfavorable way of spreading. METHODS: Single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), proteomics, and multiplexed immunohistochemistry (mIHC) were performed on GBC across multiple tumor stages to characterize the tumor microenvironment (TME), focusing specifically on the preferential enrichment of neutrophils in GBC liver invasion (GBC-LI). RESULTS: Multi-model Analysis reveals the immunosuppressive TME of GBC-LI that was characterized by the enrichment of neutrophils at the invasive front. We identified the context-dependent transcriptional states of neutrophils, with the Tumor-Modifying state being associated with oxidized low-density lipoprotein (oxLDL) metabolism. In vitro assays showed that the direct cell-cell contact between GBC cells and neutrophils led to the drastic increase in oxLDL uptake of neutrophils, which was primarily mediated by the elevated OLR1 on neutrophils. The oxLDL-absorbing neutrophils displayed a higher potential to promote tumor invasion while demonstrating lower cancer cytotoxicity. Finally, we identified a neutrophil-promoting niche at the invasive front of GBC-LI that constituted of KRT17+ GBC cells, neutrophils, and surrounding fibroblasts, which may help cultivate the oxLDL-absorbing neutrophils. CONCLUSIONS: Our study reveals the existence of a subset of pro-tumoral neutrophils with a unique ability to absorb oxLDL via OLR1, a phenomenon induced through cell-cell contact with KRT17+ GBC cells in GBC-LI.

Optimizing electronic states of Pd/WO3 nanofibers for enhanced catalytic reduction of hexavalent chromium with formic acid.

Through theoretical calculations, we show that integrating Pd with WO3 nanomaterials can trigger the interfacial electron transfer from Pd to WO3, thus upshifting the d-band center (εd) of Pd to optimize toxic hexavalent chromium (Cr(VI)) reduction. The elevated εd can derive stronger chemisorption capability toward crucial formic acid molecules, notably lowering the thermodynamic energy barrier and speeding up the kinetics process. In order to realize this concept, we synthesized unique Pd/WO3 nanofibers by loading Pd nanoparticles onto electrospun WO3 nanofibers through an in situ photodeposition technique. Extensive structural, morphological, and X-ray photoelectron spectrometer (XPS) characterizations confirm the successful formation of the above nanofibers. As anticipated, the as-designed Pd/WO3 nanofibers exhibit enhanced catalytic performance in the Cr(VI) reduction with a high turnover frequency (TOF) value of 62.12 min-1, surpassing a series of reported Pd-based catalysts. Such nanofibrous WO3-induced electronic modification of Pd with a high specific area leads to catalytic enhancement, providing a novel model for catalyst design.

A Study on the Heating and Deicing Performance of Microwave-Absorbing Asphalt Mixtures.

Road icing in winter brings challenges to traffic safety, and microwave heating and deicing technology is an effective method with the advantages of high efficiency and environmental protection. Magnetite has been widely used as a microwave-absorbing material in pavement. In this paper, magnetite powder formed by crushing natural magnetite and high-purity Fe3O4 powder after purification were mixed to replace mineral powder, and the magnetite aggregate was used to replace the limestone aggregate with the same particle size to enhance the asphalt mixtures' microwave absorption capacity. The effect of microwave heating time and microwave power on the heating of the asphalt mixtures was studied, and the heating performance of different thicknesses of the asphalt mixtures under microwave radiation was evaluated. The heating performance of the mixtures under different initial temperatures and ice layer thicknesses was also assessed. The results showed that the addition of the magnetite powder-Fe3O4 powder and the magnetite aggregate significantly enhanced the heating performance of the asphalt mixtures by microwave heating. The replacement of the magnetite powder-Fe3O4 powder, the microwave heating time, and the microwave power had positive effects on the heating efficiency of the asphalt mixtures. Moreover, the thinner asphalt mixtures had a better heating performance. The heating and deicing performance of the mixtures decreased with a decline in initial temperature. As the ice thickness increased, the deicing time of the specimen surface to reach 0 °C also increased.

High Mechanical Strength and Multifunctional Microphase-Separated Supramolecular Hydrogels Fabricated by Liquid-Crystalline Block Copolymer.

The development of multifunctional supramolecular hydrogels with high mechanical strength and multifunction is in high demand. In this work, the diblock copolymer poly(acrylamide-co-1-benzyl-3-vinylimidazolium bromide)-block-polyAzobenzene is synthesized through reversible addition-fragmentation chain transfer polymerization. The dynamic host-guest interactions between the host molecule cucurbit[8] uril and guest units are used to fabricate a 3D network of supramolecular hydrogels. Investigations on the properties of the supramolecular hydrogels show that the tensile stress of the sample is 1.46 MPa, eight times higher than that of hydrogel without liquid-crystalline block copolymer, and the self-healing efficiency of the supramolecular hydrogels at room temperature is 88.3% (fracture stress) and 100% (fracture strain) after 24 h. Results show that microphase-separated structure plays a key role in the high-strength hydrogel, whereas the host-guest interaction endows the hydrogel with self-healing properties. The supramolecular hydrogels with high mechanical strength, photo-responsivity, injectability, and biocompatibility can be used in various potential applications.

Current research scenario for biological effect of exogenous factors on microcystin synthesis.

In natural water bodies, numerous cyanobacteria have the potential to intracellularly synthesize cyanotoxins, among which microcystin (MC) is the ubiquitous toxin that has been well known to be carcinogenic for hepatocytes. MC synthesis is a complex process, which involves about 10 non-ribosomal proteins encoded by the mcy gene cluster. In the natural environments containing MC-producing cyanobacteria, a variety of external factors can affect the generation of MC by mediating the expression of synthesizing genes. These factors can be generally divided into biotic factors (e.g., daphnia, virioplankton, MC-degrading bacteria, algicidal bacteria) and abiotic factors (e.g., nutrients, physical factors, chemicals, phytochemicals, essential trace elements), which are of great significance to the effective reduction of MC. Furthermore, comparison of MC-synthesizing genes in different cyanobacterial strains was performed, and the related factors affecting MC synthesis were summarized. Then, the problems and gaps regarding the biological effect of exogenous factors on microcystin synthesis were discussed. This review article may provide new ideas for addressing the challenges and bottlenecks of MC management.

Unique insights into photocatalytic VOCs oxidation over WO3/carbon dots nanohybrids assisted by water activation and electron transfer at interfaces.

Internal electric field (IEF) at heterojunction interfaces can separate photoexcited charge carriers and promote photocatalytic performance. Here we have modified WO3 nanoplates with carbon dots (CDs) and constructed an interfacial IEF directing from CDs to WO3 with assistance of their remarkably different work functions. Such electric field drove photoexcited electrons to transport towards CDs and retained photoexcited holes to stay at WO3, achieving electron/hole spatial separation. H2O preferred chemisorption on the five-coordinated W atoms of WO3 with an elongated H-O bond and bent H-O-H angle, which allowed the activation of H2O and favorable production of ·OH radicals. The WO3/CDs (WC1) showed a superior photocatalytic activity for visible-light photooxidation of HCHO and CH3COCH3 with CO2 production rate of 411 and 188 µmol g-1 h-1, respectively, outperforming most of WO3-based photocatalysts. The enhanced photocatalytic performance correlated with the IEF-induced charge separation, favorable ·OH production and VOCs chemisorption. Our work confirms the role of CDs cocatalyst in the photocatalytic oxidation of VOCs, which will inspire enthusiasm to develop more advanced heterojunction photocatalysts involving carbon nanomaterials.

Three-Dimensional CT for Quantification of Longitudinal Lung and Pneumonia Variations in COVID-19 Patients.

Objectives: Visual chest CT is subjective with interobserver variability. We aimed to quantify the dynamic changes of lung and pneumonia on three-dimensional CT (3D-CT) images in coronavirus disease 2019 (COVID-19) patients during hospitalization. Methods: A total of 110 laboratory-confirmed COVID-19 patients who underwent chest CT from January 3 to February 29, 2020 were retrospectively reviewed. Pneumonia lesions were classified as four stages: early, progressive, peak, and absorption stages on chest CT. A computer-aided diagnostic (CAD) system calculated the total lung volume (TLV), the percentage of low attenuation areas (LAA%), the volume of pneumonia, the volume of ground-glass opacities (GGO), the volume of consolidation plus the GGO/consolidation ratio. The CT score was visually assessed by radiologists. Comparisons of lung and pneumonia parameters among the four stages were performed by one-way ANOVA with post-hoc tests. The relationship between the CT score and the volume of pneumonia, and between LAA% and the volume of pneumonia in four stages was assessed by Spearman's rank correlation analysis. Results: A total of 534 chest CT scans were performed with a median interval of 4 days. TLV, LAA%, and the GGO/consolidation ratio were significantly decreased, while the volume of pneumonia, GGO, and consolidation were significantly increased in the progressive and peak stages (for all, P < 0.05). The CT score was significantly correlated with the pneumonia volume in the four stages (r = 0.731, 0.761, 0.715, and 0.669, respectively, P < 0.001). Conclusion: 3D-CT could be used as a useful quantification method in monitoring the dynamic changes of COVID-19 pneumonia.

CT-based radiomics for predicting the rapid progression of coronavirus disease 2019 (COVID-19) pneumonia lesions.

OBJECTIVES: To develop and validate a radiomic model to predict the rapid progression (defined as volume growth of pneumonia lesions > 50% within seven days) in patients with coronavirus disease 2019 (COVID-19). METHODS: Patients with laboratory-confirmed COVID-19 who underwent longitudinal chest CT between January 01 and February 18, 2020 were included. A total of 1316 radiomic features were extracted from the lung parenchyma window for each CT. The least absolute shrinkage and selection operator (LASSO), Relief, Las Vegas Wrapper (LVW), L1-norm-Support Vector Machine (L1-norm-SVM), and recursive feature elimination (RFE) were applied to select the features that associated with rapid progression. Four machine learning classifiers were used for modeling, including Support Vector Machine (SVM), Random Forest (RF), Logistic Regression (LR), and Decision Tree (DT). Accordingly, 20 radiomic models were developed on the basis of 296 CT scans and validated in 74 CT scans. Model performance was determined by the receiver operating characteristic curve. RESULTS: A total of 107 patients (median age, 49.0 years, interquartile range, 35-54) were evaluated. The patients underwent a total of 370 chest CT scans with a median interval of 4 days (interquartile range, 3-5 days). The combination methods of L1-norm SVM and SVM with 17 radiomic features yielded the highest performance in predicting the likelihood of rapid progression of pneumonia lesions on next CT scan, with an AUC of 0.857 (95% CI: 0.766-0.947), sensitivity of 87.5%, and specificity of 70.7%. CONCLUSIONS: Our radiomic model based on longitudinal chest CT data could predict the rapid progression of pneumonia lesions, which may facilitate the CT follow-up intervals and reduce the radiation. ADVANCES IN KNOWLEDGE: Radiomic features extracted from the current chest CT have potential in predicting the likelihood of rapid progression of pneumonia lesions on the next chest CT, which would improve clinical decision-making regarding timely treatment.

MBP-activated autoimmunity plays a role in arsenic-induced peripheral neuropathy and the potential protective effect of mecobalamin.

Intake excessive arsenic (As) is related to the occurrence of peripheral neuropathy. However, both the underlying mechanism and the preventive approach remain largely unknown. In the present study, As treatment significantly decreased the mechanical withdrawal threshold and increased the titer of anti-myelin basic protein antibody in rats, accompanied with damaged BNB. The levels of inflammatory cytokines and proteolytic enzymes were also significantly upregulated. However, administration of MeCbl in As-treated rats significantly reversed the decline in hindfoot mechanical withdrawal threshold, as well as BNB failure and sciatic nerve inflammation. Repeated As treatment in athymic nude mice indicated that sciatic nerve inflammation and mechanical hyperalgesia were T cell-dependent. These data implicated that MBP-activated autoimmunity and the related neuroinflammation probably contributed to As-induced mechanical hyperalgesia and MeCbl exerted a protective role probably via maintenance the integrity of BNB and inhibition of neuroinflammation.

Corrigendum: Programmable Ce6 Delivery via Cyclopamine Based Tumor Microenvironment Modulating Nano-System for Enhanced Photodynamic Therapy in Breast Cancer.

[This corrects the article DOI: 10.3389/fchem.2019.00853.].

A multifunctional SN38-conjugated nanosystem for defeating myelosuppression and diarrhea induced by irinotecan in esophageal cancer.

A combination of chemotherapy and phototherapy has been proposed as a promising treatment for esophageal cancer (EC). Irinotecan as a first-line treatment option is widely prescribed for metastatic EC, however, its clinical application is extremely restricted by the low conversion rate to SN38, severe myelosuppression and diarrhea. As a more potent active metabolite of irinotecan, SN38 is a better substitution for irinotecan, but the poor water solubility and the difficulty of encapsulation hindered its medical application. Herein, a multifunctional SN38-conjugated nanosystem (FA-PDA@PZM/SN38@BSA-MnO2, denoted as FA-PPSM) is designed for overcoming the above-mentioned drawbacks and achieving collaborative chemotherapy, photodynamic therapy (PDT) and photothermal therapy (PTT). The tumor acidic microenvironment induces decomposition of BSA-MnO2 nanoparticles into O2 and Mn2+, thus enhancing oxygen-dependent PDT efficacy; meanwhile, Mn2+ can be employed as a magnetic resonance imaging (MRI) contrast agent. Under 650 and 808 nm laser irradiation, the FA-PPSM nanocomposites exhibit superior antitumor efficacy in Eca-109-tumor bearing mice. Notably, there is low gastrointestinal toxicity and myelosuppression in the FA-PPSM treated mice compared with those treated with irinotecan (alone). Taken together, this work highlights the great potential of the FA-PPSM nanocomposites for MRI-guided chemotherapy in combination with endoscopic light therapy for esophageal cancer.

A Cu9S5 nanoparticle-based CpG delivery system for synergistic photothermal-, photodynamic- and immunotherapy.

Despite its great potential in cancer therapy, phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), often cause metastasis of tumors. Immunotherapy has revolutionized the cancer treatment owing to the capability of activating immune system to eliminate tumors. However, the integration of phototherapy and immunotherapy in a single nanoagent for cancer therapy is still a challenging task. Here, we fabricated (Cu9S5@mSiO2-PpIX@MnO2@CpG (CSPM@CpG)) as a synergistic therapeutic model for phototherapy enhanced immunotherapy. The intracellular uptake of cytosine-phosphate-guanine (CpG) promoted the infiltration of cytotoxic T lymphocytes (CTLs) in tumor tissue, further stimulating the production of interferon gamma (IFN-γ) and remarkably elevating the immune response level. Excellent anti-tumor effects have been achieved by synergistic PTT/PDT/immunotherapy. The metastasis of tumors was effectively inhibited by the immune response of CpG. Thus, our proposed work provides a strategy to combine phototherapy with immunotherapy to enhance the therapeutic efficiency and further inhibit metastasis of tumors.

The Efficiency of Primary Health Care Institutions in the Counties of Hunan Province, China: Data from 2009 to 2017.

This study aimed to estimate the efficiency and its influencing factors of Primary Health Care Institutions (PHCIs) in counties in Hunan Province, China, and put forward feasible suggestions for improving the efficiency of PHCIs in Hunan Province. We applied the Input-Oriented Data Envelopment Analysis (DEA) method and the Malmquist Index Model to estimate the efficiency of PHCIs in 86 counties in Hunan Province from 2009 to 2017. Then, the Tobit model was used to estimate the factors that influence the efficiency of PHCIs. Since the implementation of the new health-care reform in 2009, the number of health resources in PHCIs in Hunan Province has increased significantly, but most counties' PHCIs remain inefficient. The efficiency of PHCIs is mainly affected by the total population, city level, the proportion of health technicians and the proportion of beds, but the changes in per capita GDP have not yet played a significant role in influencing efficiency. In the future, the efficiency of PHCIs should be improved by increasing medical technology skills and enthusiasm of health technicians and by improving the payment policies of medical insurance funds.

Post-synthesis strategy to integrate porphyrinic metal-organic frameworks with CuS NPs for synergistic enhanced photo-therapy.

Multifunctional nanotheranostic systems with both therapeutic and imaging functions are highly desired for the development of more effective and less toxic anti-tumor drugs. Herein, a simple but effective method is reported to fabricate a novel PCN-CuS-FA-ICG-based nanoplatform for dual-modal imaging-guided synergistic photothermal/photodynamic therapy. Porphyrinic metal-organic frameworks with CuS NPs are obtained in aqueous solution via a simple post-synthesis strategy. Furthermore, to obtain a more effective therapy, indocyanine green (ICG) was incorporated into the multifunctional theranostic platform to promote the photothermal therapeutic effect. The as-prepared PCN-CuS-FA-ICG not only exhibits an excellent 1O2 generation efficiency under 650 nm irradiation to achieve remarkable photodynamic cell killing, but also presents outstanding photothermal conversion under 808 nm irradiation to destroy tumor tissues by hyperthermia. In particular, the nanotherapeutic agent realized fluorescence and thermal imaging dual-modal imaging-guided cancer treatment. Meanwhile, in vivo experiments confirmed the evident accumulation of nanoparticles (NPs) at local tumors, and tumor growth was inhibited obviously via synergistic photothermal/photodynamic therapy with negligible side effects.

Functional role of bloom-forming cyanobacterium Planktothrix in ecologically shaping aquatic environments.

Diverse metabolic behaviors endow microorganisms with various ecological functions, and metabolic activities of microbial species may affect the environmental conditions of their habitats. In this study, genome-guided analysis of Planktothrix spp. first divided these strains into six distinct groups, and comparisons of Planktothrix genomes revealed the inter- and intra-species variation. Prediction of central metabolism showed the functional diversity with regard to uptake of carbon, nitrogen, and sulfur sources. As the carbon-fixing microorganisms, Planktothrix isolates played a critical role in transforming the atmospheric carbon into organic carbon-the waterbodies' pool of available carbon. Diazotrophic lifestyle in certain Planktothrix strains may provide valuable avenues for supporting the equilibrium community. Furthermore, genome mining supported the exploration of biosynthetic gene clusters dedicated to cyanobacterial natural products, mainly including non-ribosomal peptide, polyketide, cyanobactin, and microviridin. Notably, some Planktothrix strains had the potential to non-ribosomally synthesize the microcystin (MC), a potent cyclic heptapeptide toxin, and MC-mediated cycling might strengthen the association between MC-producing and MC-degrading microorganisms. In short, genome-wide study of Planktothrix strains advances our current understanding of their metabolic potential and especially ecological roles in shaping natural environments.

Insights into ecological roles and potential evolution of Mlr-dependent microcystin-degrading bacteria.

Over decades many studies have focused on the biodegradation of microcystins (MCs), and some Mlr-dependent MC-degrading bacteria were recorded, but the ecological functions, metabolic traits, and potential evolution of these organisms remain poorly understood. In this study, 16S rRNA-based phylogeny unraveled a wide range of genetic diversity across bacterial lineage, accompanied by re-evaluation of taxonomic placement of some MC-degrading species. Genome-wide comparison showed that considerable genes unique in individual organisms were identified, suggesting genetic differentiation among these Mlr-dependent MC-degrading bacteria. Notably, analyses of metabolic profiles first revealed the presence of functional genes involved in phenylacetate biodegradation in the specialized genomic regions, and mlr gene cluster was located around the neighborhood. The identification of transposable elements further indicated that these genomic regions might undergo horizontal gene transfer events to recruit novel functionalities, suggesting an adaptive force driving genome evolution of these organisms. In short, phylogenetic and genetic content analyses of Mlr-dependent MC-degraders shed light on their metabolic potential, ecological roles, and bacterial evolution, and expand the understanding of ecological status of MCs biodegradation.

Clinical Utility of a Nomogram for Predicting 30-Days Poor Outcome in Hospitalized Patients With COVID-19: Multicenter External Validation and Decision Curve Analysis.

Aim: Early detection of coronavirus disease 2019 (COVID-19) patients who are likely to develop worse outcomes is of great importance, which may help select patients at risk of rapid deterioration who should require high-level monitoring and more aggressive treatment. We aimed to develop and validate a nomogram for predicting 30-days poor outcome of patients with COVID-19. Methods: The prediction model was developed in a primary cohort consisting of 233 patients with laboratory-confirmed COVID-19, and data were collected from January 3 to March 20, 2020. We identified and integrated significant prognostic factors for 30-days poor outcome to construct a nomogram. The model was subjected to internal validation and to external validation with two separate cohorts of 110 and 118 cases, respectively. The performance of the nomogram was assessed with respect to its predictive accuracy, discriminative ability, and clinical usefulness. Results: In the primary cohort, the mean age of patients was 55.4 years and 129 (55.4%) were male. Prognostic factors contained in the clinical nomogram were age, lactic dehydrogenase, aspartate aminotransferase, prothrombin time, serum creatinine, serum sodium, fasting blood glucose, and D-dimer. The model was externally validated in two cohorts achieving an AUC of 0.946 and 0.878, sensitivity of 100 and 79%, and specificity of 76.5 and 83.8%, respectively. Although adding CT score to the clinical nomogram (clinical-CT nomogram) did not yield better predictive performance, decision curve analysis showed that the clinical-CT nomogram provided better clinical utility than the clinical nomogram. Conclusions: We established and validated a nomogram that can provide an individual prediction of 30-days poor outcome for COVID-19 patients. This practical prognostic model may help clinicians in decision making and reduce mortality.

Combined effects of ambient air pollution and home environmental factors on low birth weight.

BACKGROUND: Low birth weight (LBW) remains a major public health problem worldwide, yet its crucial environmental risk factors are still unclear. OBJECTIVE: To examine the association between LBW (term and preterm LBW) and prenatal exposure to ambient air pollution and home environmental factors as well as their combination, in order to identify critical time window for exposure and key outdoor and indoor factors in LBW development. METHODS: A cohort study of 3509 preschool children was performed in Changsha, China during the period 2011-2012. A questionnaire was conducted to survey each child's birth outcome and each mother's exposure to home environmental factors including parental smoking, new furniture, redecoration, mold/damp stains, window pane condensation, and household pets during pregnancy. Maternal exposure to inhalable particulate matter (PM10), industrial air pollutant (SO2), and traffic air pollutant (NO2) was estimated during different time windows of gestation, including conception month, three trimesters, birth month, and whole gestation. Associations of term and preterm LBW with ambient air pollutants and home environmental factors were assessed by multiple logistic regression models in terms of odds ratio (OR) with 95% confidence interval (CI). RESULTS: Term LBW (TLBW) was significantly associated with exposure to ambient PM10 during pregnancy, with OR (95% CI) = 1.47 (1.00-2.14) for per IQR increase after adjustment for the covariates and home environmental factors. Specifically, we identified the significant association in early phase of pregnancy including conception month (1.90, 1.09-3.30) and the first trimester (1.72, 1.10-2.69). We further found that TLBW was significantly related with parental smoking at home, OR (95% CI) = 2.17 (1.09-4.33). However, no association was observed for preterm LBW (PLBW). The TLBW risk of ambient air pollution and home environmental factors was independent each other and hence the combined exposure to ambient PM10 and indoor parental smoking caused the highest risk. Sensitivity analysis suggested that foetus with younger mothers were significantly more susceptible to risk of indoor parental smoking, while those with smaller house and cockroaches were more sensitive to risk of outdoor PM10 exposure. CONCLUSION: Prenatal exposure to combined outdoor and indoor air pollution, particularly in critical window(s) during early pregnancy, significantly increases the risk of term LBW.