Imaging the Meissner effect in hydride superconductors using quantum sensors.

By directly altering microscopic interactions, pressure provides a powerful tuning knob for the exploration of condensed phases and geophysical phenomena1. The megabar regime represents an interesting frontier, in which recent discoveries include high-temperature superconductors, as well as structural and valence phase transitions2-6. However, at such high pressures, many conventional measurement techniques fail. Here we demonstrate the ability to perform local magnetometry inside a diamond anvil cell with sub-micron spatial resolution at megabar pressures. Our approach uses a shallow layer of nitrogen-vacancy colour centres implanted directly within the anvil7-9; crucially, we choose a crystal cut compatible with the intrinsic symmetries of the nitrogen-vacancy centre to enable functionality at megabar pressures. We apply our technique to characterize a recently discovered hydride superconductor, CeH9 (ref. 10). By performing simultaneous magnetometry and electrical transport measurements, we observe the dual signatures of superconductivity: diamagnetism characteristic of the Meissner effect and a sharp drop of the resistance to near zero. By locally mapping both the diamagnetic response and flux trapping, we directly image the geometry of superconducting regions, showing marked inhomogeneities at the micron scale. Our work brings quantum sensing to the megabar frontier and enables the closed-loop optimization of superhydride materials synthesis.

Experimental Limits on Solar Reflected Dark Matter with a New Approach on Accelerated-Dark-Matter-Electron Analysis in Semiconductors.

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

Molecular rectification induced by magnetization alignment in organic-ferromagnetic devices.

Spin-dependent transport in ferromagnet/organic-ferromagnet/ferromagnet junctions is investigated theoretically under different alignment of magnetization orientations. The results demonstrate a significant current rectification at low bias voltages, and the rectifying direction relies on the relative magnetization orientation in each component. The orbital analysis demonstrates two underlying mechanisms for the rectification, the slight structural asymmetry of the molecule from spin radicals and distinct spin match between conducting electrons and the magnetic molecule upon the reversal of bias. The latter is responsible for the strong low-bias rectification and relies on the magnetization alignment. The effects of parameter strength, temperature and size on the rectification are discussed. This work explores a new route to achieve high-performance molecular rectifiers operating at low bias with controlled rectifying direction.

Prenatal exposure to PM2.5 components and the risk of different types of preterm birth and the mediating effect of pregnancy complications: a cohort study.

OBJECTIVES: This study aims to reveal the single and mixed associations of PM2.5 and its components with very, moderately, and late preterm births and to explore the potential mediating role of pregnancy complications in PM2.5-induced preterm birth. STUDY DESIGN: This was a retrospective cohort study. METHODS: We enrolled 168,852 mothers and matched the concentrations of PM2.5 and its five components (OM, SO42-, BC, NO3-, and NH4+) based on their geographical location. Next, we used generalized linear models, quantile g-computation, and mediation analysis to evaluate the associations of PM2.5 and its components with very, moderately, and late preterm births and the mediating role of pregnancy complications. RESULTS: Prenatal exposure to PM2.5 and its components was associated with preterm birth, and the association was strongest in the third trimester. Preterm birth was associated with co-exposure to a mixture of PM2.5 components in the third trimester, and the contributions of NO3-, NH4+, and BC to the risk of preterm birth were positive. Meanwhile, pregnancy complications mediated PM2.5-induced preterm birth. Moreover, very and moderately preterm births were associated with PM2.5 and its components in the second and third trimesters, and very and late preterm births were associated with co-exposure to a mixture of PM2.5 components in the third trimester. CONCLUSIONS: Later exposure to PM2.5 during pregnancy will cause earlier preterm birth. Targeted and positive interventions for anthropogenic sources of specific PM2.5 components and pregnancy complications are helpful for preterm birth prevention.

[Ameliorative effect of rare ginsenosides on reproductive injury induced by cyclophosphamide in female rats: based on metabonomics].

Objective: To investigate the effect of rare ginsenosides (RGS) on reproductive injury induced by cyclophosphamide (CP) in female rats. Methods: Twenty-four female rats were divided into four groups [normal control (NC), RGS, CP, and CP+RGS group] with 6 rats in each group. CP group (the model group) and CP+RGS group (the treatment group) were intraperitoneally injected with CP 30 mg/kg for 5 days for modeling, and CP+RGS group was given RGS intragastric intervention. General growth status of rats in each group was observed, the organ index was calculated, and the pathological changes of ovary, uterus, liver and kidney were observed by hematoxylin-eosin staining. Serum levels of estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), pro-inflammatory factors interleukin (IL) 6, IL-1ß, tumor necrosis factor-α were detected. The urine samples were collected after RGS treatment for metabonomics analysis. Metabolomic profiling based on ultra performance liquid chromatography (UPLC) coupled with mass spectrometry (MS) was used to analyze and determine the urine metabolites of rats in each group. Results: Compared with NC group, the ovary index of CP group [(0.054±0.015) %] was significantly decreased (P<0.05), the uterus index [(0.293±0.036) %] and estradiol level [(62.9±6.4) pmol/L] were significantly decreased (all P<0.01), serum levels of FSH, LH, IL-6 and IL-1ß [(20.4±1.0) U/L, (29.0±3.0) U/L, (185.4±28.6) ng/L, (72.9±2.0) ng/L, respectively] were significantly increased (all P<0.01). Compared with CP group, the ovary index in CP+RGS group [(0.075±0.010) %] was significantly increased (P<0.05), serum estradiol level [(122.1±16.2) pmol/L] was significantly increased (P<0.01), serum FSH, IL-1ß and IL-6 levels [(16.7±1.0) U/L, (111.8±17.4) ng/L, (60.1±2.2) ng/L, respectively] were significantly decreased (all P<0.01). Metabonomics analysis results showed that, a total of 352 metabolites were detected in urine, of which 12 were found to be potential markers associated with reproductive injury according to the screening standard. After treatment with RGS, differential metabolites were improved in the direction of NC group. Pathway enrichment suggests that the therapeutic effect of RGS was related to multiple metabolic pathways, including purine metabolism and taurine and hypotaurine metabolism. Conclusion: RGS might reduce inflammation and thus ameliorate the damage caused by CP to the reproductive system of female rats by affecting purine metabolism and other pathways.

[Monitoring and analysis on host animals of hemorrhagic fever with renal syndrome in Henan Province from 2019 to 2022].

Objective: To investigate the distribution and hantavirus (HV) carrying state in host animals of hemorrhagic fever with renal syndrome (HFRS) in Henan Province from 2019 to 2022. Methods: Host animal monitoring was carried out at the monitoring sites of HFRS in Henan Province. The real-time fluorescence quantitative PCR was used to detect hantavirus in rat lungs. The types of hantavirus were analyzed. The positive samples were sequenced and then sequence homology and variation were analyzed. Results: A total of 1 308 rodents were captured from 2019 to 2022, 16 specimens of rat lungs tested positive for hantavirus nucleic acid. The positive rate of HV was 1.22% (16/1 308). According to type, the positive rate of HV in Apodius agrarius was the highest (68.75%, 11/16). According to distribution, the positive rate of HV in field samples was the highest (2.50%, 12/480), and the positive rate of HV in residential samples was 0.53% (4/759). The typing results of 16 positive samples showed that all viruses were hantavirus type Ⅰ (hantaan virus). The positive samples were sequenced and eight S gene fragments (GenBank number: OQ681444-OQ681451) and six M gene fragments (OQ681438-OQ681443) were obtained. The S and M gene fragments were similar to the Shaanxi 84FLi strain and Sichuan SN7 strain. Phylogenetic analysis of S and M gene fragments showed that they all belonged to the hantaan virus-H5 subtype. Amino acid sequence analysis revealed that, compared with the hantaan virus vaccine strain 84FLi, the 74th amino acid encoded by eight S fragments was replaced by aspartamide with serine. Tryptophan was replaced by glycine at the 14th position of Gn region in XC2022047, and isoleucine was replaced by alanine at the 359 position of XC2022022 and XC2022024. Conclusion: The hantavirus carried by host animals in Henan Province from 2019 to 2022 belongs to the type Ⅰ (hantaan virus), and Apodemus agrarius is still the dominant host animal of the hantaan virus. Compared with the vaccine strains, amino acid sites are replaced in the immune epitopes of the S and M gene fragments.

[A case of pleural metastasis of malignant peripheral nerve sheath tumor].

Malignant peripheral nerve sheath tumor (MPNST) frequently metastasizes to the lungs, although pleural metastasis is rare. This article reported a case of pleural metastasis of MPNST. The patient was a young man who presented with 1 week of shortness of breath with dry cough. He had a history of malignant peripheral nerve sheath tumor. The patient was diagnosed with MPNST pleural metastasis after a thoracoscopic pleural biopsy, which revealed short spindle cell hyperplasia, immunohistochemical staining for S-100(+), SOX-10(+), Ki-67(+) with a positive index of 20%, and H3K27Me3(-) in the pleural pathology.

[An analysis of disease burden of occupational lung cancer in China from 1990 to 2019].

Objective: To analyze the trend of disease burden, including mortality and disability-adjusted life years (DALYs) , of occupational lung cancer in China from 1990 to 2019. Methods: In June 2022, the data of occupational lung cancer was obtained from Global Burden of Disease Study 2019 (GBD) . Excel summarized the data, and the mortality rate, DALYs and age-normalized rate were analyzed. Applying Joinpoint Regression Program software annual Percentage Change (APC) and Average Annual Percentage Change Rate (AAPC) . Results: Age-standardized mortality rates ranged from 2.41 in 1990 to 3.14 per 100 000 in 2019, with gender differences and a positive correlation with age. DALYs increased from 580, 000 person-years in 1990 to 1 509 900 person-years in 2019. The rate of standardized DALYs increased from 63.03 per 100 000 in 1990 to 71.65 per 100 000 in 2019. According to the annual percentage change (APC) analysis by Joinpoint Regression Program software, the age-normalized mortality and DALY rates decreased from 2011 to 2016, and the increasing trend from 2016 to 2019 was significantly lower than that before 2011. And the increase at this stage was not statistically significant. The APCC values of mortality rate, standardized mortality rate, DALYs rate and changed DALYs rate were 3.28, 0.92, 2.64 and 0.44, respectively, and the trend differences were statistically significant. Conclusion: The disease burden of occupational lung cancer is increasing from 1990 to 2019. Lung cancer screening should be carried out among high-risk populations to achieve early diagnosis and treatment.

"Triple-low" radiation dose bronchial artery CT angiography before bronchial artery embolisation: a feasibility study.

AIM: To explore the feasibility of a "triple-low" dose (low tube voltage, low tube current, and low contrast agent volume) bronchial artery computed tomography (CT) angiography (CTA) to replace routine dose bronchial artery CTA before bronchial artery embolisation (BAE). MATERIALS AND METHODS: CTA was obtained from 60 patients with body mass index (BMI) < 30 kg/m2 using a 256 multi-section iCT system, and they were divided into two groups: (1) group A: 100 kVp, 100 mAs, 50 ml contrast medium (CM); (2) group B: 120 kVp, automatic tube current modulation (ACTM), 80 ml CM. CT attenuation of the thoracic aorta, image noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated, and subjective image quality scores and traceability scores assessed. The effective radiation dose was calculated. RESULTS: The radiation dose was reduced by 79.7% in group A compared to group B (p<0.05). The CT attenuation of the thoracic aorta was increased by approximately 13% in group A compared to group B (p<0.05). Higher image noise, lower SNR, and CNR were obtained in group A compared to group B (all p<0.05). Both subjective image quality scores and traceability scores did not differ between groups A and B (both p>0.05). CONCLUSION: It is feasible to use the "triple-low" dose CTA protocol for patients with a body mass index (BMI) < 30 kg/m2. The radiation dose was reduced by 79.7%, and the dose of contrast medium was reduced by 37.5% to ensure the diagnostic value.

Factors associated with early failure of the femoral neck system (FNS) in patients with femoral neck fractures.

BACKGROUND: Femoral neck system (FNS) is a new type of internal fixation system which has been widely used for treating femoral neck fractures (FNFs).Compared with other internal fixation methods, FNS is minimally invasive and stable, and often achieves satisfactory short-term efficacy.Early failure of FNS (EFFNS) is not uncommon, however, there are few literatures and reports on factors associated with EFFNS.This study aimed to survey the prevalence and risk factors of EFFNS. METHODS: We retrospectively analysed 62 patients with FNFs and underwent FNS fixation between 2019 and 2021. Demographic data, clinical characteristics, radiographic features and treatment process were described. Multifactor logistic regression analysis was used to analyse the different influencing factors. RESULTS: Out of the 62 FNFs patients, 10 patients (16.1%) developed EFFNS, including 6 cases of severe femoral neck shortening, 2 cases of screw-out, 1 case of avascular necrosis of the femoral head and 1 case of nonunion. In the failure group, all patients were younger than 65 years old, which was significantly higher than 59.6% in the healing group (P = 0.012). There were no significant differences in sex(P = 0.490), BMI (P = 0.709), injured side (P = 0.312), injury mechanism (P = 0.617), reduction method(P = 0.570),femoral neck-shaft angle(P = 0.545), Pauwels classification (P = 0.564) and Garden classification (P = 0.195). Moreover, we not found that Garden classification (P = 0.464) and age (P = 0.128) were statistically significant risk factors for EFFNS at multivariate analysis. CONCLUSION: In this study, sex, BMI, injury side, injury mechanism, reduction method, Pauwels angle, femoral neck-shift angle, Pauwels classification and Garden classification were excluded as EFFNS risk factors. Moreover, our study demonstrated that age and Garden classification were not significant risk factors at multivariate analysis. TRIAL REGISTRATION: ChiCTR, ChiCTR2100051360. Registered on 21 September, 2021. https://www.chictr.org.cn/index.aspx .

[Preliminary analysis of neuroprotective effects of capillary fascia preservation recurrent laryngeal nerve anatomical method in right level â ¥ dissection].

Objective: To investigate the application and effect of capillary fascia preservation between the recurrent laryngeal nerve (RLN) and common carotid artery (fascia preservation method) in nerve protection when dissecting right level Ⅵ lymph nodes for patients with papillary thyroid carcinoma. Methods: A retrospective cohort study enrolling 195 patients with papillary thyroid carcinoma undergoing right level Ⅵ lymph node dissection in Beijing Tongren Hospital from March 2021 to August 2022 was carried out. The RLN was dissected by fascia preservation method in study group and by routine method in control group. The intraoperative electrical signal amplitude of the RLN, the number of dissected lymph nodes, and the postoperative complications were recorded and analyzed. Results: A total of 195 patients (study group: 94 cases, control group: 101 cases) were collected. There were 71 males and 124 females, with the median age of 32 (39, 51) years. In the study group, the total number of right level Ⅵ lymph nodes was significantly larger than the number of right Ⅵa level lymph nodes [8 (6, 11) vs 6 (4, 8), P<0.001]. There were no significant differences between the two groups in the number of level Ⅵa or level Ⅵb lymph nodes [Ⅵa: 6 (4, 8) vs 5 (3, 7), P=0.373; Ⅵb: 3 (1, 4) vs 2 (1, 4), P=0.337] and metastasis rate [Ⅵa: 51.1% (48/94) vs 52.5% (53/101), P=0.844; Ⅵb: 12.8% (12/94) vs 15.8% (16/101), P=0.541]. The ratio of electromyography (EMG) amplitude R2 in lower level Ⅵ and entry into larynx (grouped as>90%, 50%~90%,<50%) in the study group was significantly higher than that in the control group (P<0.001). No significant differences were detected between the two groups in temporary RLN paralysis [1.1% (1/94) vs 2.0% (2/101), P=1.000]. Conclusions: Fascia preservation method can decrease the stimulus and traction to RLN and preserve the capillary network serving RLN. It can thoroughly dissect lymph nodes and decrease the injury of RLN.

[Association between chronic lung diseases and the risk of lung cancer in UK Biobank: observational and Mendelian randomization analyses].

Objective: To investigate the association between chronic lung diseases and the risk of lung cancer. Methods: Using UK Biobank (UKB) survey data, 472 397 participants who had not previously been diagnosed with cancer and whose self-reported sex was consistent with their genetic sex were studied. Information on the prevalence of previous chronic lung diseases, general demographic characteristics and the prevalence of lung cancer was collected using baseline questionnaires and national health system data. The multivariate Cox proportional risk regression model was used to analyze the association between four previous chronic lung diseases (asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and interstitial pulmonary disease) and the risk of lung cancer. A total of 458 526 participants with genotype data in the observational study were selected as research objects, and the closely related and independent genetic loci with four chronic lung diseases were selected as instrumental variables, and the association between four chronic lung diseases and the risk of lung cancer was analyzed by Mendelian randomization (MR). The dose-response relationship between genetic risk score and the risk of lung cancer in different chronic lung diseases was evaluated using a restricted cubic spline function. Results: The age [M (Q1, Q3)] of the subjects was 57 (50, 63) years old, and there were 3 516 new cases of lung cancer (0.74%) during follow-up. The multivariate Cox proportional hazard regression model analysis showed that previous chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis were associated with the risk of lung cancer, about 1.61 (1.49-1.75) and 2.61 (1.24-5.49), respectively. MR Studies showed that genetically predicted chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis were associated with the risk of lung cancer, with HR (95%CI) of 1.10 (1.03-1.19) and 1.04 (1.01-1.08), respectively. The results of restricted cubic spline function analysis showed that the risk of lung cancer increased linearly with the increase of genetic risk scores for chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis (P<0.05). Neither observational studies nor Mendelian randomization analysis found an association between previous asthma or interstitial lung disease and the risk of lung cancer (both P values>0.05). Conclusion: Chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis are potential risk factors for lung cancer.

[Prediction models for respiratory event types in OSA patients based on hypoxic parameters].

Objective: To analyze the hypoxic parameters in patients with obstructive sleep apnea (OSA), to explore the difference and association between different types of respiratory events and to construct predictive models for respiratory event types. Methods: Fifty patients [including 41 males and 9 females with age 18-74(45.72±13.39) years ] with OSA diagnosed by polysomnography (PSG) were selected for retrospective analysis, and all respiratory events with pulse oximetry (SpO2) desaturation in the recorded overnight data were divided into hypopnea group (Hyp, 3 316), obstructive apnea group (OA, 5 552), central apnea group (CA, 1 088) and mixed apnea group (MA, 1 369) according to the type of events, and all event records were exported separately from the PSG software as comma-separated variable (.csv) files, which were imported and analyzed using the in-house built Matlab software. A total of 13 hypoxic parameter differences were compared among the four groups, including minimum oxygen saturation of events (e-minSpO2), the depth of desaturation (ΔSpO2), the duration of desaturation and resaturation (DSpO2), the duration of desaturation (d.DSpO2), duration of resaturation (r.DSpO2), duration of SpO2<90% (T90), duration of SpO2<90% during desaturation (d.T90), duration of SpO2<90% during resaturation (r.T90), area under the curve of SpO2<90% (ST90), area under the curve of SpO2<90% during desaturation (d.ST90), area under the curve of SpO2<90% during resaturation (r.ST90), oxygen desaturation rate (ODR) and oxygen resaturation rate (ORR). Hyp model (H), OA model (O), CA model (C) and MA model (M) were constructed respectively; group differences for the different hypoxia parameters were assessed using single factor analysis and Kruskal-Wallis H test. For different categories of respiratory events, binary logistic regression was used to identify the variables included in the regression model. Receiver operating characteristic (ROC) curves were generated to assess and compare the sensitivity, specificity, positive predictive value and negative predictive value of the four models, thereby gauging the predictive precision of each model. Results: ΔSpO2, ODR, ORR, T90, d.T90, r.T90, ST90, d.ST90 and r.ST90 for each type of respiratory events showed MA>OA>CA>Hyp, and e-minSpO2 showed MA

[Clinical features and long-term prognosis of primary biliary cholangitis in patients with past hepatitis B virus infection].

Objective: To investigate the clinical features and long-term prognosis of primary biliary cholangitis (PBC) in patients with past hepatitis B virus (HBV) infection. Methods: 353 cases with PBC who visited the Liver Disease Center of Beijing Friendship Hospital Affiliated to Capital Medical University between January 2000 and January 2018 were retrospectively analyzed and were divided into the past HBV infection group (156 cases) and the no HBV infection group (197 cases). The two groups' baseline clinical features were compared. Ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, and long-term liver transplantation-free survival rate were compared through outpatient and telephone follow-up. Results: PBC with past HBV infection had a significantly reduced female proportion compared to the no HBV infection group (91.9% vs. 79.5%, P = 0.001). However, there were no statistically significant differences in age, biochemical indices, immunological indicators, platelet count, cirrhosis proportion, and others. Ursodeoxycholic acid biochemical response rate was reduced in patients with past HBV infection at the end of one year of treatment, but the difference was not statistically significant (65.8% vs. 78.2%, P = 0.068). In addition, there were no statistically significant differences between the GLOBE score (0.57 vs. 0.59, P = 0.26) and UK-PBC 5-year (2.87% vs. 2.87%, P = 0.38), 10-year (9.29% vs. 8.2%, P = 0.39) and 15-year liver transplantation rates (16.6% vs. 14.73%, P = 0.39). Lastly, the overall 5-year liver transplantation-free survival rate had no statistically significant difference between the two groups of patients (86.4% vs. 87.5%, P = 0.796). Conclusion: Primary biliary cholangitis had no discernible effect in terms of age at onset, biochemical indices, immunological indicators, cirrhosis proportion, ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, or overall liver transplantation-free survival rate in patients with past hepatitis B virus infections.

[Current application and prospect of accurate navigation technology in orthopaedic trauma].

In the past decades,a dramatic development of navigation technology in orthopaedic surgery has been witnessed. By assisting the localization of surgical region,verification of target bony structure,preoperative planning of fixation,intraoperative identification of planned entry point and direction of instruments or even automated insertion of implants,its ability and potential to reduce operation time,intraoperative radiation,surgical trauma,and improve accuracy has been proved. However,in contrast to the widespread use of navigation technology in arthroplasty,orthopaedic tumor,and spine surgery,its application in orthopaedic trauma is relatively less. In this manuscript,the main purpose is to introduce the technical principles of navigation devices,outline the current clinical application of navigation systems in orthopaedic trauma,analyze the current challenges confronting its further application in clinical practice and its prospect in the future.

Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML.

The BCL-2 inhibitor venetoclax combined with hypomethylating agents or low-dose cytarabine represents an important new therapy for older or unfit patients with acute myeloid leukemia (AML). We analyzed 81 patients receiving these venetoclax-based combinations to identify molecular correlates of durable remission, response followed by relapse (adaptive resistance), or refractory disease (primary resistance). High response rates and durable remissions were typically associated with NPM1 or IDH2 mutations, with prolonged molecular remissions prevalent for NPM1 mutations. Primary and adaptive resistance to venetoclax-based combinations was most commonly characterized by acquisition or enrichment of clones activating signaling pathways such as FLT3 or RAS or biallelically perturbing TP53. Single-cell studies highlighted the polyclonal nature of intratumoral resistance mechanisms in some cases. Among cases that were primary refractory, we identified heterogeneous and sometimes divergent interval changes in leukemic clones within a single cycle of therapy, highlighting the dynamic and rapid occurrence of therapeutic selection in AML. In functional studies, FLT3 internal tandem duplication gain or TP53 loss conferred cross-resistance to both venetoclax and cytotoxic-based therapies. Collectively, we highlight molecular determinants of outcome with clinical relevance to patients with AML receiving venetoclax-based combination therapies.

Constraints on Sub-GeV Dark Matter-Electron Scattering from the CDEX-10 Experiment.

We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4 kg·day dataset from the CDEX-10 experiment. Using a novel calculation technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m_{χ} larger than 80 MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m_{χ} larger than 90 MeV/c^{2} with heavy mediators and m_{χ} larger than 100 MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.

Exotic Dark Matter Search with the CDEX-10 Experiment at China's Jinping Underground Laboratory.

A search for exotic dark matter (DM) in the sub-GeV mass range has been conducted using 205 kg day data taken from a p-type point contact germanium detector of the CDEX-10 experiment at China's Jinping underground laboratory. New low-mass dark matter searching channels, neutral current fermionic DM absorption (χ+A→ν+A) and DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), have been analyzed with an energy threshold of 160 eVee. No significant signal was found; thus new limits on the DM-nucleon interaction cross section are set for both models at the sub-GeV DM mass region. A cross section limit for the fermionic DM absorption is set to be 2.5×10^{-46} cm^{2} (90% C.L.) at DM mass of 10 MeV/c^{2}. For the DM-nucleus 3→2 scattering scenario, limits are extended to DM mass of 5 and 14 MeV/c^{2} for the massless dark photon and bound DM final state, respectively.

Three novel structural variations at the major histocompatibility complex and IL12B predispose to psoriasis.

BACKGROUND: Structural variations (SVs; defined as DNA variants ≥ 50 base pairs) have been associated with various complex human diseases. However, research to screen the whole genome for SVs predisposing to psoriasis is lacking. OBJECTIVES: To investigate the association of SVs and psoriasis. METHODS: Using imputation, we performed a genome-wide screen of SVs on five independent cohorts with 45 386 participants from the Han Chinese population. Fine-mapping analysis, genetic interaction analysis and RNA expression analysis were conducted to explore the mechanism of SVs. RESULTS: In total, we obtained 4535 SVs and identified two novel deletions [esv3608550, odds ratio (OR) 2·73 (P < 2·00 × 10-308 ); esv3608542, OR 0·47 (P = 7·40 × 10-28 )] at 6q21·33 (major histocompatibility complex), one novel Alu element insertion [esv3607339; OR 1·22 (P = 1·18 × 10-35 )] at 5q33·3 (IL12B) and confirmed one previously reported deletion [esv3587563; OR 1·30 (P = 9·52 × 10-60 )] at 1q21·2 (late cornified envelope) for psoriasis. Fine-mapping analysis including single-nucleotide polymorphisms (SNPs) and small insertions/deletions revealed that esv3608550 and esv3608542 were independently associated with psoriasis, and a novel independent SNP [rs9378188; OR, 1·65 (P = 3·46 × 10-38 )] was identified at 6q21·33. By genetic interaction analysis and RNA expression analysis, we speculate that the association of two deletions at 6q21·33 with psoriasis might relate to their influence on the expression of HLA-C. CONCLUSIONS: We have constructed the most comprehensive SV map for psoriasis thus far and enriched the genetic architecture and pathogenesis of psoriasis, and highlight the non-negligible impact of SVs on complex diseases.

Bifocal 532/1064 nm alternately illuminated photoacoustic microscopy for capturing deep vascular morphology in human skin.

BACKGROUND: As a promising technology, photoacoustic microscopy (PAM) plays a critical role in diagnosis and assessment of dermatological conditions by providing subtle vascular networks non-invasively. However, the established PAMs are insufficient for clinical dermatology when faced with complex structures of human skin instead of animal models owing to high melanin content and superimposed vasculature for Asians, which cannot balance the spatial resolution and the imaging depth. OBJECTIVES: To evaluate the ability of bifocal 532/1064-nm alternately illuminated photoacoustic microscopy (BF-PAM) to non-invasively reveal the morphological structure of human skin for improving the diagnosis and therapeutic efficacy of skin diseases. METHODS: A BF-PAM was developed to capture biopsy-like information of human skin from epidermis to hypodermis. The optical foci of the two excitation beams are staggered in the axial direction to form an extended depth-of-field, which can maintain the lateral resolution and the contrast of PA image. RESULTS: The imaging capability of the BF-PAM was demonstrated by depicting the vascular morphology of multilayered skin with imaging depth of ˜3 mm. Furtherly, vascular malformations in port-wine stains skin were quantitatively assessed without the need for any contrast agent, and the distribution, depth and diameter of the ectatic vessels can determine an optimal treatment protocol for port-wine stains lesions. CONCLUSIONS: The quantitative vascular morphology in the dermis can be used to accurately assess vascular characteristics, in which case it enables clinicians to determine optimum treatment parameters in individual patients. As a non-invasive imaging technique, BF-PAM holds great potential to provide objective assessment to enhance the therapeutic efficacy. ETHICAL STATEMENT: The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT20200184) and registered with Chinese Clinical Trial Registry (ChiCTR2000034400). Before skin imaging, written informed consent was taken from all individual participants.