Chirality is an asymmetric property widely found in nature. Here, we propose and demonstrate experimentally the spontaneous emergence of chirality in an on-chip ultrahigh-Q whispering-gallery ...microresonator, without broken parity or time-reversal symmetry. This counterintuitive effect arises due to the inherent Kerr-nonlinearity-modulated coupling between clockwise and counterclockwise propagating waves. Above an input threshold of a few hundred microwatts, the initial chiral symmetry is broken spontaneously, and the counterpropagating output ratio exceeds 20∶1 with bidirectional inputs. The spontaneous chirality in an on-chip microresonator holds great potential in studies of fundamental physics and applied photonic devices.
Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency ...of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next‐generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non‐BRCA1/2 gene. Major mutant non‐BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non‐BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER‐2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non‐BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non‐BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.
What's new?
The prevalence of mutations in breast cancer predisposition genesare not well investigated in Asia. We assessed germline mutations of 40 cancer susceptibility genes in 937 consecutive selected breast cancer patients from 26 centers of China, and discovered 23.8% of participates carried the pathogenic mutation, including 6.8% with mutations in non‐BRCA1/2 genes, while TP53 and PALB2 had a relatively high mutation rates (1.9% and 1.2%).There was no factors predicted for detrimental mutations in non‐BRCA1/2 genes when treated as a whole.
The present study aimed to discover novel susceptibility loci associated with risk of rheumatoid arthritis (RA).
We performed a new genome-wide association study (GWAS) in Chinese subjects (1027 RA ...cases and 2879 controls) and further conducted an expanded meta-analysis with previous GWAS summary data and replication studies. The functional roles of the associated loci were interrogated using publicly available databases. Dual-luciferase reporter and cytokine assay were also used for exploring variant function.
We identified five new susceptibility loci (
,
,
,
and
; p
<5.00E-08) with same effect direction in each study cohort. The sensitivity analyses showed that the genetic association of at least three loci was reliable and robust. All these lead variants are expression quantitative trait loci and overlapped with epigenetic marks in immune cells. Furthermore, genes within the five loci are genetically associated with risk of other autoimmune diseases, and genes within four loci are known functional players in autoimmunity, which supports the validity of our findings. The reporter assay showed that the risk allele of rs8030390 in
have significantly increased reporter activity in HEK293T cells. In addition, the cytokine assay found that the risk allele of rs244672 in
was most significantly associated with increased plasma IL-17A levels in healthy controls. Finally, identified likely causal genes in these loci significantly interacted with RA drug targets.
This study identified novel RA risk loci and highlighted that comprehensive genetic study can provide important information for RA pathogenesis and drug therapy.
Hand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV‐A71) is a contagious viral disease, and toll‐like receptors (TLRs) play essential roles in resisting the pathogen. The aim of this ...study was to assess the potential relationship between several TLRs polymorphisms and the HFMD severity in a Chinese children population. A total of 328 Chinese children with HFMD were included in the present study. The polymorphisms of TLR3 (rs3775290, rs3775291, rs3775296, rs1879026, rs5743312, rs5743313, rs5743303, rs13126816, and rs3775292), TLR4 (rs4986790, rs4986791, rs2149356, rs11536889, and rs41426344), TLR7 (rs179009, rs179010, rs179016, rs3853839, rs2302267, rs1634323, and rs5741880), and TLR8 (rs3764880, rs2159377, rs2407992, rs5744080, rs3747414, rs3764879, and rs5744069) genes were selected. The study indicated that individuals with the GG genotype of TLR3 single‐nucleotide polymorphism rs1879026 had a higher risk of developing severe cases (GG vs. GT: OR = 1.875; 95% CI, 1.183–2.971; p = .007). Meanwhile, TLR3 rs3775290 CC genotype and C allele were associated with lower disease severity in females (CC vs. CT: OR = 0.350; 95% CI, 0.163–0.751; p = .006; C vs. T: OR = 0.566; 95% CI, 0.332–0.965; p = .036). TLR3 rs3775291 CC genotype showed 2.537 folds higher risk of developing severe cases in females (CC vs. CT: OR = 2.537; 95% CI, 1.108–5.806; p = .026). Moreover, TLR3 rs1879026 GG genotype was found to be related to increased risk of severe cases in males (GG vs. GT: OR = 2.076; 95% CI, 1.144–3.768; p = .016). The current findings show that the genetic variants of TLR3 rs1879026, rs3775290, and rs3775291 are associated with the severity of EV‐A71‐associated HFMD in a Chinese children population.
To investigated the association between single nucleotide polymorphisms (SNPs) in microRNA-146a (miR-146a) gene and susceptibility of rheumatoid arthritis (RA).
We systemically extracted the genetic ...data of miR-146a from previous genome-wide association studies (GWASs) of RA. Subsequently, we performed a replication study in an independent Chinese cohort for selected variant. A meta-analysis combined the previous GWASs with the replication study was also conducted. The epigenetic annotation and cytokine assay were used for exploring potential variant function.
The extracted genetic association data from three previous GWASs showed that the allele T of functional SNP rs2431697 increased RA susceptibility. The significant association for the SNP was also found in the Chinese replication cohort (OR = 1.24, 95% CI = 1.06-1.46, p = 8.69E-03). The estimated effect size for this SNP was larger in Asian population than that in European population (Asian meta-analysis: OR = 1.15, 95% CI = 1.09-1.22, p = 4.37E-07; Tran-ethnic meta-analysis: OR = 1.07, 95% CI = 1.04-1.10, p = 1.79E-06). The cytokine assay also showed that the risk allele T of the SNP rs2431697 is inversely associated with plasma TNF-α levels in health controls (p = .016).
In summary, this study supports that genetic variant in miR-146a gene is associated with RA risk.
KEY MESSAGES
The association between SNPs in miR-146a gene and susceptibility of RA was unclear.
We investigated the genetic association using GWASs data and a replication study.
The SNP rs2431697 in miR-146a gene is associated with RA risk.
HMOs (human milk oligosaccharides) are the third most important nutrient in breast milk. As complex glycans, HMOs play an important role in regulating neonatal intestinal immunity, resisting viral ...and bacterial infections, displaying anti-inflammatory characteristics, and promoting brain development. Although there have been some previous reports of HMOs, a detailed literature review summarizing the structure–activity relationships and dose-dependent effects of HMOs is lacking. Hence, after introducing the structures and synthetic pathways of HMOs, this review summarizes and categorizes identified structure–function relationships of HMOs. Differential mechanisms of different structural HMOs utilization by microorganisms are summarized. This review also emphasizes the recent advances in the interactions between different health benefits and the variance of dosage effect based on in vitro cell tests, animal experiments, and human intervention studies. The potential relationships between the chemical structure, the dosage selection, and the physiological properties of HMOs as functional foods are vital for further understanding of HMOs and their future applications.
Introduction
Whether lung ultrasound (LUS) can be used for pathogenic diagnosis remains controversial. This study was conducted to clarify whether ultrasound has diagnostic value for etiology.
...Methods
A total of 135 neonatal pneumonia patients with an identified pathogen were enrolled from the newborn intensive care units of 10 tertiary hospitals in China. The study ran from November 2020 to December 2021. The infants were divided into various groups according to pathogens, time of infection, gestational age, and disease severity. The distribution of pleural line abnormalities, B‐line signs, and pulmonary consolidation, as well as the incidence of air bronchogram and pleural effusion based on LUS, were compared between these groups.
Results
There were significant differences in pulmonary consolidation. The sensitivity and specificity of the diagnosis of severe pneumonia based on the extent of pulmonary consolidation were 83.3% and 85.2%, respectively. The area under the receiver operating characteristic curve for the identification of mild or severe pneumonia based on the distribution of pulmonary consolidation was 0.776.
Conclusion
LUS has good performance in diagnosing and differentiating the severity of neonatal pneumonia but cannot be used for pathogenic identification in the early stages of pneumonia.
To explore the influence of rapid urbanization development on the accumulation of 16 priority PAHs in urban environment, thirty-three surface sediments from city lakes in different urbanized areas of ...Shanghai were collected to evaluate the occurrence characteristic and source apportionment of PAHs. The concentrations of Σ16PAHs in lake surface sediments ranged from 55.7 to 4928 ng g−1 with a mean value of 1131 ng g−1 (standard deviation, 1228 ng g−1), of which 4-, 5- and 6-ring PAHs were the dominant components. Spatial distribution of PAHs in lake surface sediments showed a significantly declining trend along with a decreasing urbanization gradient (one-way ANOVA, p < .05). Two hotspots of sediment PAHs were mainly distributed at highly urbanized areas with intensive population density and heavy traffic activities and at burgeoning industrial towns in the suburb. Source apportionment of total PAHs identified by a constrained positive matrix factorization model revealed that vehicle emission and combustion of coal, biomass and natural gas were the absolutely predominant sources, respectively accounting for 55.0% and 40.45% of total PAHs burden in lake sediments. Land use regression (LUR) models were successfully developed to evaluate spatial variation of PAHs contamination in urban sediments based on their significant correlations with residential land, commercial land, traffic variables, industrial sources, and population density. All PAH compounds showed strong associations with one or two source indicators (the traffic congestion index and the number of industrial sources), with the fitting R2 varying from 0.529 to 0.984. Our findings suggest that energy consumption related to land use activities obviously promoted PAH accumulations in urban sediment environment during rapid development of urbanization and industrialization in Shanghai.
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•PAH contaminations were investigated in surface sediments of Shanghai park lakes.•PAH concentrations in lake sediments showed significant urbanization disparity.•Combustion of fossil fuels was the predominant sources of PAHs in lake sediments.•Traffic ingestion index and industrial source were crucial factors in LUR models.
Intensive industrial and traffic activities caused by rapid urbanization promoted PAHs contamination in park lake sediments.
The accuracy of GNSS/Acoustic seafloor geodetic calibration is greatly influenced by the temporal variation of sound velocity, especially in the vertical direction. Aiming at correcting of the ...unknown parameters related to both the positions and the sound velocity, this paper proposes a step-by-step inversion scheme based on moving survey data. The proposed method firstly estimates the horizontal normalized travel time delay with sound ray tracing strategy and then computes the horizontal position with circle line observations. We reconstructed an inversion scheme for extracting the surface sound velocity disturbance (SSVD) and corrected the vertical position from cross line data. The SSVD is decomposed into a sum of different period disturbances, and a new SSVD is reconstructed by combining the long period disturbance and short period disturbance. The proposed algorithm is verified by the South China Sea experiment for GNSS/Acoustic seafloor geodetic calibration. The results demonstrate that the new method can take the effects of sound velocity variation into consideration and improve the precision of the vertical position, which is superior to the least squares (LS), the single-difference LS for seafloor geodetic calibration.
Differentiated thyroid cancer (DTC) is commonly diagnosed in women of child-bearing age, but whether pregnancy influences the prognosis of DTC remains controversial. This study aimed to summarize ...existing evidence regarding the association of pregnancy with recurrence risk in patients previously treated for DTC.
We searched PubMed, Embase, Web of Science, Cochrane, and Scopus based on the prespecified protocol registered at PROSPERO (CRD42022367896). After study selection, two researchers independently extracted data from the included studies. For quantitative data synthesis, we used random-effects meta-analysis models to pool the proportion of recurrence (for pregnant women only) and odds ratio (OR; comparing the risk of recurrence between the pregnancy group and the nonpregnancy group), respectively. Then we conducted subgroup analyses to explore whether risk of recurrence differed by response to therapy status or duration of follow-up time. We also assessed quality of the included studies.
A total of ten studies were included. The sample size ranged from 8 to 235, with participants' age at pregnancy or delivery ranging from 28 to 35 years. The follow-up time varied from 0.1 to 36.0 years. The pooled proportion of recurrence in all pregnant patients was 0.13 (95% confidence intervals CI: 0.06-0.25; I2 : 0.58). Among six included studies reporting response to therapy status before pregnancy, we observed a trend for increasingly higher risk of recurrence from excellent, indeterminate, and biochemically incomplete to structurally incomplete response to therapy ( Ptrend <0.05). The pooled risk of recurrence in the pregnancy group showed no evidence of a significant difference from that in the nonpregnancy group (OR: 0.75; 95% CI: 0.45-1.23; I2 : 0). The difference in follow-up time (below/above five years) was not associated with either the proportion of recurrence in all pregnant patients ( P >0.05) or the OR of recurrence in studies with a comparison group ( P >0.05). Two included studies that focused on patients with distant metastasis also did not show a significant difference in disease recurrence between pregnancy and nonpregnancy groups (OR: 0.51 95% CI: 0.14-1.87; I2 : 59%).
In general, pregnancy appears to have a minimal association with the disease recurrence of DTC with initial treatment. Clinicians should pay more attention to progression of DTC among pregnant women with biochemical and/or structural persistence.
PROSPERO, https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42022367896.
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