Quantum-metric-induced nonlinear transport in a topological antiferromagnet.

The Berry curvature and quantum metric are the imaginary part and real part, respectively, of the quantum geometric tensor, which characterizes the topology of quantum states1. The Berry curvature is known to generate a number of important transport phenomena, such as the quantum Hall effect and the anomalous Hall effect2,3; however, the consequences of the quantum metric have rarely been probed by transport measurements. Here we report the observation of quantum-metric-induced nonlinear transport, including both a nonlinear anomalous Hall effect and a diode-like non-reciprocal longitudinal response, in thin films of a topological antiferromagnet, MnBi2Te4. Our observations reveal that the transverse and longitudinal nonlinear conductivities reverse signs when reversing the antiferromagnetic order, diminish above the Néel temperature and are insensitive to disorder scattering, thus verifying their origin in the band-structure topology. They also flip signs between electron- and hole-doped regions, in agreement with theoretical calculations. Our work provides a means to probe the quantum metric through nonlinear transport and to design magnetic nonlinear devices.

Spatial Filtering of Interlayer Exciton Ground State in WSe2/MoS2 Heterobilayer.

Long-life interlayer excitons (IXs) in transition metal dichalcogenide (TMD) heterostructure are promising for realizing excitonic condensates at high temperatures. Critical to this objective is to separate the IX ground state (the lowest energy of IX state) emission from other states' emissions. Filtering the IX ground state is also essential in uncovering the dynamics of correlated excitonic states, such as the excitonic Mott insulator. Here, we show that the IX ground state in the WSe2/MoS2 heterobilayer can be separated from other states by its spatial profile. The emissions from different moiré IX modes are identified by their different energies and spatial distributions, which fits well with the rate-diffusion model for cascading emission. Our results show spatial filtering of the ground state mode and enrich the toolbox to realize correlated states at elevated temperatures.

Layer-dependent correlated phases in WSe2/MoS2 moiré superlattice.

Electron correlation plays an essential role in the macroscopic quantum phenomena in the moiré heterostructure, such as antiferromagnetism and correlated insulating phases. Unlike the phenomena where the interaction involves only electrons in one layer, the interaction of distinct phases in two or more layers represents a new horizon forward, such as the one in the Kondo lattice model. Here, using interlayer excitons as a probe, we show that the interlayer interactions in heterobilayers of tungsten diselenide and molybdenum disulfide (WSe2/MoS2) can be electrically switched on and off, resulting in a layer-dependent correlated phase diagram, including single-layer, layer-selective, excitonic-insulator and layer-hybridized regions. We demonstrate that these correlated phases affect the interlayer exciton non-radiative decay pathways. These results reveal the role of strong correlation on interlayer exciton dynamics and pave the way for studying the layer-resolved strong correlation behaviour in moiré heterostructures.

Robust Nuclear Spin Polarization via Ground-State Level Anticrossing of Boron Vacancy Defects in Hexagonal Boron Nitride.

Nuclear spin polarization plays a crucial role in quantum information processing and quantum sensing. In this work, we demonstrate a robust and efficient method for nuclear spin polarization with boron vacancy (V_{B}^{-}) defects in hexagonal boron nitride (h-BN) using ground-state level anticrossing (GSLAC). We show that GSLAC-assisted nuclear polarization can be achieved with significantly lower laser power than excited-state level anticrossing, making the process experimentally more viable. Furthermore, we have demonstrated direct optical readout of nuclear spins for V_{B}^{-} in h-BN. Our findings suggest that GSLAC is a promising technique for the precise control and manipulation of nuclear spins in V_{B}^{-} defects in h-BN.

Somatic mutation of targeted sequencing identifies risk stratification in advanced ovarian clear cell carcinoma.

BACKGROUND: Ovarian clear cell carcinoma (OCCC) is a unique subtype of epithelial ovarian cancer. Advanced OCCC display a poor prognosis. Therefore, we aimed to make risk stratification for precise medicine. METHODS: We performed a large next generation sequencing (NGS) gene panel on 44 patients with OCCC in FIGO stage II-IV. Then, by machine learning algorithms, including extreme gradient boosting (XGBoost), random survival forest (RSF), and Cox regression, we screened for feature genes associated with prognosis and constructed a 5-gene panel for risk stratification. The prediction efficacy of the 5-gene panel was compared with FIGO stage and residual disease by receiver operating characteristic curve and decision curve analysis. RESULTS: The feature mutated genes related to prognosis, selected by machine learning algorithms, include MUC16, ATM, NOTCH3, KMT2A, and CTNNA1. The 5-gene panel can effectively distinguish the prognosis, as well as platinum response, of advanced OCCC in both internal and external cohorts, with the predictive capability superior to FIGO stage and residual disease. CONCLUSIONS: Mutations in genes, including MUC16, ATM, NOTCH3, KMT2A, and CTNNA1, were associated with the poor prognosis of advanced OCCC. The risk stratification according to these genes demonstrated acceptable prediction power of prognosis and platinum response, suggesting the potential to be a novel target for precision medicine.

Spin Defects in hBN assisted by Metallic Nanotrenches for Quantum Sensing.

The omnipresence of hexagonal boron nitride (hBN) in devices embedding two-dimensional materials has prompted it as the most sought after platform to implement quantum sensing due to its testing while operating capability. The negatively charged boron vacancy (VB-) in hBN plays a prominent role, as it can be easily generated while its spin population can be initialized and read out by optical means at room-temperature. But the lower quantum yield hinders its widespread use as an integrated quantum sensor. Here, we demonstrate an emission enhancement amounting to 400 by nanotrench arrays compatible with coplanar waveguide (CPW) electrodes employed for spin-state detection. By monitoring the reflectance spectrum of the resonators as additional layers of hBN are transferred, we have optimized the overall hBN/nanotrench optical response, maximizing thereby the luminescence enhancement. Based on these finely tuned heterostructures, we achieved an enhanced DC magnetic field sensitivity as high as 6 × 10-5 T/Hz1/2.

2-Deoxy-D-glucose simultaneously targets glycolysis and Wnt/ß-catenin signaling to inhibit cervical cancer progression.

Cervical cancer is one of the most common female malignant tumors, with typical cancer metabolism characteristics of increased glycolysis flux and lactate accumulation. 2-Deoxy-D-glucose (2-DG) is a glycolysis inhibitor that acts on hexokinase, the first rate-limiting enzyme in the glycolysis pathway. In this research, we demonstrated that 2-DG effectively reduced glycolysis and impaired mitochondrial function in cervical cancer cell lines HeLa and SiHa. Cell function experiments revealed that 2-DG significantly inhibited cell growth, migration, and invasion, and induced G0/G1 phase arrest at non-cytotoxic concentrations. In addition, we found that 2-DG down-regulated Wingless-type (Wnt)/ß-catenin signaling. Mechanistically, 2-DG accelerated the degradation of ß-catenin protein, which resulted in the decrease of ß-catenin expression in both nucleus and cytoplasm. The Wnt agonist lithium chloride and ß-catenin overexpression vector could partially reverse the inhibition of malignant phenotype by 2-DG. These data suggested that 2-DG exerted its anti-cancer effects on cervical cancer by co-targeting glycolysis and Wnt/ß-catenin signaling. As expected, the combination of 2-DG and Wnt inhibitor synergistically inhibited cell growth. It is noteworthy that, down-regulation of Wnt/ß-catenin signaling also inhibited glycolysis, indicating a similar positive feedback regulation between glycolysis and Wnt/ß-catenin signaling. In conclusion, we investigated the molecular mechanism by which 2-DG inhibits the progression of cervical cancer in vitro, elucidated the interregulation between glycolysis and Wnt/ß-catenin signaling, and preliminarily explored the effect of combined targeting of glycolysis and Wnt/ß-catenin signaling on cell proliferation, which provides more possibilities for the formulation of subsequent clinical treatment strategies.

[68Ga]Ga-FAPI-04 PET/CT in the evaluation of epithelial ovarian cancer: comparison with [18F]F-FDG PET/CT.

PURPOSE: To compare the efficacy of [68Ga]Ga-FAPI-04 PET/CT in primary or recurrent tumors and metastatic lesions of epithelial ovarian cancer (EOC) with that of fluorine-18 fluorodeoxyglucose ([18F]F-FDG) PET/CT. METHODS: Forty-nine patients (median age, 57 years; IQR, 51-66 years) with histologically proven primary or relapsed EOC were enrolled. Participants underwent [18F]F-FDG and [68Ga]Ga-FAPI-04 PET/CT. The detection rate, diagnostic accuracy, semiquantitative parameters, tumor staging, and clinical management of the tracers were compared. The diagnostic performance of [18F]F-FDG and [68Ga]Ga-FAPI-04 PET/CT was evaluated and compared using surgical pathology. Differences between methods regarding the peritoneal cancer index (PCI) using preoperative imaging, surgical PCI, and tumor markers (CA125, HE4) were also assessed regarding peritoneal metastases. RESULTS: Among the 49 patients, 28 had primary EOC; 21 had relapsed EOC. [68Ga]Ga-FAPI-04 PET/CT outperformed [18F]F-FDG PET/CT in detecting peritoneal metastases (96.8% vs. 83.0%; p < 0.001), retroperitoneal (99.5% vs. 91.4%; p < 0.001), and supradiaphragmatic lymph node metastases (100% vs. 80.4%; p < 0.001). Compared with [18F]F-FDG, [68Ga]Ga-FAPI-04 showed higher SUVmax for peritoneal metastases (17.31 vs. 13.68; p = 0.026) and retroperitoneal (8.72 vs. 6.56; p < 0.001) and supradiaphragmatic lymph node metastases (6.39 vs. 4.20; p < 0.001). Moreover, [68Ga]Ga-FAPI-04 PET/CT showed higher sensitivity compared with [18F]F-FDG PET/CT for detecting metastatic lymph nodes (80.6% vs. 61.3%; p = 0.031) and peritoneal metastases (97.5% vs. 75.9%; p < 0.001), using surgical pathology as the gold standard. Compared with [18F]F-FDG PET/CT, [68Ga]Ga-FAPI-04 PET/CT led to an upgrade in 14.3% and 33.3% of treatment-naive and relapse participants, resulting in management changes in 10.7% and 19.0% of the patients, respectively. The median PCIFAPI scores were significantly higher than PCIFDG (15 vs. 11; p < 0.001) and positively correlated with CA125 and HE4 levels and surgical PCI. CONCLUSION: [68Ga]Ga-FAPI-04 PET/CT achieved higher sensitivity than [18F]F-FDG PET/CT in the detection and diagnosis of lymph node and peritoneal metastases, suggesting advantages regarding the preoperative staging of patients with EOC and, thereby, improving treatment decision-making. TRIAL REGISTRATION: NCT05034146. Registered February 23, 2021.

Strain Quantum Sensing with Spin Defects in Hexagonal Boron Nitride.

Hexagonal boron nitride is not only a promising functional material for the development of two-dimensional optoelectronic devices but also a good candidate for quantum sensing thanks to the presence of quantum emitters in the form of atom-like defects. Their exploitation in quantum technologies necessitates understanding their coherence properties as well as their sensitivity to external stimuli. In this work, we probe the strain configuration of boron vacancy centers (VB-) created by ion implantation in h-BN flakes thanks to wide-field spatially resolved optically detected magnetic resonance and submicro Raman spectroscopy. Our experiments demonstrate the ability of VB- for quantum sensing of strain and, given the omnipresence of h-BN in 2D-based devices, open the door for in situ imaging of strain under working conditions.

Quantum Interference of Resonance Fluorescence from Germanium-Vacancy Color Centers in Diamond.

Resonance fluorescence from a quantum emitter is an ideal source to extract indistinguishable photons. By using the cross-polarization to suppress the laser scattering, we observed resonance fluorescence from GeV color centers in diamond at cryogenic temperature. The Fourier-transform-limited line width emission with T2/2T1 ∼ 0.86 allows for two-photon interference based on single GeV color center. Under pulsed excitation, the separated photons exhibit a Hong-Ou-Mandel quantum interference above classical limit, whereas the continuous-wave excitation leads to a coalescence time window of 1.05 radiative lifetime. In addition, we demonstrated a single-shot readout of spin states with a fidelity of 74%. Our experiments lay down the foundation for building a quantum network with GeV color centers in diamond.

PROTACs in Epigenetic Cancer Therapy: Current Status and Future Opportunities.

The epigenetic regulation of gene functions has been proven to be strongly associated with the development and progression of cancer. Reprogramming the cancer epigenome landscape is one of the most promising target therapies in both treatments and in reversing drug resistance. Proteolytic targeted chimeras (PROTACs) are an emerging therapeutic modality for selective degradation via the native ubiquitin-proteasome system. Rapid advances in PROTACs have facilitated the exploration of targeting epigenetic proteins, a lot of PROTAC degraders have already been designed in the field of epigenetic cancer therapy, and PROTACs targeting epigenetic proteins can better exploit target druggability and improve the mechanistic understanding of the epigenetic regulation of cancer. Thus, this review focuses on the progress made in the development of PROTAC degraders and PROTAC drugs targeting epigenetics in cancer and discusses challenges and future opportunities for the field.

Excited-State Optically Detected Magnetic Resonance of Spin Defects in Hexagonal Boron Nitride.

Negatively charged boron vacancy (V_{B}^{-}) centers in hexagonal boron nitride (h-BN) are promising spin defects in a van der Waals crystal. Understanding the spin properties of the excited state (ES) is critical for realizing dynamic nuclear polarization. Here, we report zero-field splitting in the ES of D_{ES}=2160 MHz and its associated optically detected magnetic resonance (ODMR) contrast of 12% at cryogenic temperature. In contrast to nitrogen vacancy (NV^{-}) centers in diamond, the ODMR contrast of V_{B}^{-} centers is more prominent at cryotemperature than at room temperature. The ES has a g factor similar to the ground state. The ES photodynamics is further elucidated by measuring the level anticrossing of the V_{B}^{-} defects under varying external magnetic fields. Our results provide important information for utilizing the spin defects of h-BN in quantum technology.

Coherent Manipulation with Resonant Excitation and Single Emitter Creation of Nitrogen Vacancy Centers in 4H Silicon Carbide.

Silicon carbide (SiC) has become a key player in the realization of scalable quantum technologies due to its ability to host optically addressable spin qubits and wafer-size samples. Here, we have demonstrated optically detected magnetic resonance (ODMR) with resonant excitation and clearly identified the ground state energy levels of the NV centers in 4H-SiC. Coherent manipulation of NV centers in SiC has been achieved with Rabi and Ramsey oscillations. Finally, we show the successful generation and characterization of single nitrogen vacancy (NV) center in SiC employing ion implantation. Our results highligh the key role of NV centers in SiC as a potential candidate for quantum information processing.

VPS33B negatively modulated by nicotine functions as a tumor suppressor in colorectal cancer.

The biological role of vacuolar protein sorting 33B (VPS33B) has not been examined in colorectal cancer (CRC). We report that VPS33B was downregulated in dextran sulfate sodium/azoxymethane (DSS/AOM) -induced CRC mice models and nicotine-treated CRC cells via the PI3K/AKT/c-Jun pathway. Reduced VPS33B is an unfavorable factor promoting poor prognosis in human CRC patients. VPS33B overexpression suppressed CRC proliferation, intrahepatic metastasis and chemoresistance of cisplatin (DDP) in vivo and in vitro through modulating the epidermal growth factor receptor (EGFR)/RAS/ERK/c-Myc/p53/miR-133a-3p feedback loop and the downstream cell cycle or EMT-related factors. Furthermore, NESG1 as a newly identified tumor suppressor interacted with VPS33B via colocalization in the cytoplasm, and it was stimulated by VPS33B through the downregulation of RAS/ERK/c-Jun-mediated transcription. NESG1 also activated VPS33B expression via the RAS/ERK/c-Jun pathway. Suppression of NESG1 increased cell growth, migration and invasion via the reversion of the VPS33B-modulating signal in VPS33B-overexpressed cells. Taken together, VPS33B as a tumor suppressor is easily dysregulated by chemical carcinogens and it interacts with NESG1 to modulate the EGFR/RAS/ERK/c-Myc/p53/miR-133a-3p feedback loop and thus suppress the malignant phenotype of CRC.

Patients With Lung Cancer Have High Susceptibility of COVID-19: A Retrospective Study in Wuhan, China.

Patients with lung cancer are presumed to be at high risk from COVID-19 infection due to underlying malignancy. A total of 31 COVID-19 patients with pre-diagnosed lung cancer and 186 age and sex matched COVID-19 patients without cancer in 6 hospitals in Wuhan, China were identified in our study. There was a significantly higher level of IL-6 in lung cancer group showed by multifactorial analysis. The restricted mean survival time in 10, 20, and 53 days in COVID-19 patients with lung cancer were ealier than non-cancer COVID-19 patients in the same observation time (all P values < 0.05). Our results indicated that pre-diagnosed lung cancer was associated with higher morbidity and mortality in COVID-19 patients.

Elastic Net-Based Identification of a Multigene Combination Predicting the Survival of Patients with Cervical Cancer.

BACKGROUND The objective of the present study was to identify prognostication biomarkers in patients with cervical cancer. MATERIAL AND METHODS Survival related genes were identified in The Cancer Genome Atlas (TCGA) cervical cancer study, and they were included into an elastic net regularized Cox proportional hazards regression model (CoxPH). The genes that their coefficients that were not zero were combined to build a prognostication combination. The prognostication performance of the multigene combination was evaluated and validated using Kaplan-Meier curve and univariate and multivariable CoxPH model. Meanwhile, a nomogram was built to translate the multigene combination into clinical application. RESULTS There were 37 survival related genes identified, 9 of which were integrated to build a multigene combination. The area under the curve (AUC) of receiver operating characteristic (ROC) curve at 1-year, 3-year, 5-year, and 7-year in the training set were 0.757, 0.744, 0.799, and 0.854, respectively, and the multigene combination could stratify patients into significantly different prognostic groups (hazard ratio [HR]=0.2223, log-rank P<0.0001). Meanwhile, the corresponding AUCs in the test set was 0.767, 0.721, 0.735, and 0.703, respectively, and the multigene combination could classify patients into different risk groups (HR=0.3793, log-rank P=0.0021). The multigene combination could stratify patients with early stage and advanced stage into significantly different survival groups in the training set and test set. The prognostication performance of the multigene combination was better compared with 3 existing prognostic signatures. Finally, a multigene containing nomogram was developed. CONCLUSIONS We developed a multigene combination which could be treated as an independent prognostic factor in cervical cancer and be translated into clinical application.

Thioridazine upregulates programmed cell death 4 to induce apoptosis in nasopharyngeal carcinoma through the PI3K/Akt signalling pathway.

Thioridazine (THZ) has been identified as a potential regulator of tumour progression, and programmed cell death 4 (PDCD4) has been reported as a novel tumour suppressor. This study aimed to investigate the link between PDCD4 and THZ in the regulation of nasopharyngeal cancer (NPC) cell proliferation. The effect of THZ on NPC cells was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays. Then, the involvement of apoptosis and cell cycle in the THZ-mediated regulation of cell viability was assessed by flow cytometry. Related mRNAs and proteins were subsequently examined by real-time PCR and western blot, respectively. After transfection with the PDCD4-siRNA, pGC-FU-GFP-PDCD4 vector and phosphoinositide 3-kinase (PI3K) inhibitor Ly294002, we investigated the antagonistic effects of THZ and PDCD4 on NPC-related protein expression. MTT assays showed that THZ treatment suppressed cell viability. THZ-treated cells were arrested at the G1/G0 phase and showed a significantly increased apoptotic fraction. Furthermore, PDCD4-siRNA antagonized THZ treatment and promoted NPC cell proliferation. Western blot analysis showed that PDCD4 overexpression or PI3K inhibition by LY294002 significantly reduced the expression of phospho-PI3K, phospho-Akt, phospho-mammalian target of rapamycin and phospho-p70s6k, but not their total protein levels. In conclusion, our findings show that THZ and PDCD4 exert antagonistic effects on NPC cell proliferation, probably through the PI3K/Akt pathway. Moreover, these results provide an insight into the mechanism by which THZ targets PDCD4 in NPC cell lines and suggest that the ectopic expression of PDCD4 is a potential therapeutic strategy.

Prevalence and type-specific distribution of human papillomavirus infection among women in mid-western rural, Nepal- A population-based study.

BACKGROUND: Cervical cancer is the most common cancer among women in Nepal. The prevalence of human papillomavirus (HPV) 16 and or HPV 18 among women with cervical pre-cancer and cancer is higher than the incidence of HPV in the world population. The population-based epidemiological data of HPV in the general population in most parts of the country remains unknown. The objective of this study was to assess the prevalence and type distribution of HPV infection and association of abnormal cytology with high risk HPV infection among women in mid-western rural, Nepal. METHODS: A population-based cross sectional study was conducted in Jumla, one of the most remote districts in Nepal. A total of 1050 cervical samples were collected from married and non- pregnant women aged 20-65 years during mobile Cervical Cancer Screening Clinics conducted from May 2016 to January 2017. The presence of HPV DNA was firstly confirmed by HPV consensus PCR using PGMY09/PGMY11 designed primers, then HPV positive samples were further genotyped by the membrane hybridization method to detect the 21 high-risk HPV (HR-HPV) and low-risk HPV types. The prevalence of HR-HPV among women with normal and abnormal cytology was calculated. Data were analyzed using SPSS software for Windows. P < 0.05 was considered statistically significant. RESULTS: A total of 998 women were eligible for this study with the mean age 32.6 ± 8.6 years, and the mean marital age was 16.7 ± 3.8 years. The overall prevalence of HPV infections was 19.7%. HR-HPV and low-risk HPV were 11.7 and 8.7% respectively. The six most common HR-HPV types were HPV16, 39, 58, 33, 51 and 18. HR-HPV infection among the women with abnormal and normal cytology was of 27.3 and 10.8% respectively. CONCLUSIONS: There was a higher prevalence of HR-HPV infection among women living in Jumla than other parts of Nepal. This study provides preliminary information on overall HPV and type-specific HR-HPV prevalence, HR-HPV 16, 39, 58, 33, 51, and 18 are the most prevalent genotypes in this region. The data contribute to the epidemiological knowledge about HPV and type-specific HR-HPV genotypes prevalence in mid-Western Nepal.

The availability, price and affordability of essential antibacterials in Hubei province, China.

BACKGROUND: China ranks first amongst the countries for the abuse of antibacterials. Essential antibacterials could help solve the problem. The aim of the work is to evaluate the availability, price and affordability of essential antibacterials in Hubei province, China. METHOD: The standardized methodology developed by the World Health Organization and Health Action International was used to collect data on the availability and prices of 16 antibacterials in 5 cities of Hubei province, China. RESULTS: First, in total, the median availability of originator brands and lowest-priced generics for the essential antibacterials was low, 3.0% (0.0, 18.2%) and 33.3% (0.0, 87.9%) for each, respectively. Second, the median price ratio of originator brands for the antibacterials was 20.30 (4.71, 35.80), while for generics, it was 0.49 (0.07, 1.18). Third, the affordability of originator brands for the antibacterials was 28.14 (21.70, 41.90) times the daily wages of an unskilled government worker, while for generics, the affordability was 0.35 (0.04, 6.11). Finally, we found that in Hubei province, lowest-priced generics for essential antibacterials with (fairly) high availability and relatively low price included Amoxicillin/Clavulanic Acid, Ceftazidime, Metronidazole, Gentamicin Sulfate and Ceftriaxone. CONCLUSION: The prices of lowest-priced generics for essential antibacterials in Hubei province were reasonable, and in tertiary hospitals the availability was the highest, while in secondary and primary hospitals, it was relatively lower. Originator brands were not only extremely expensive but also difficult to obtain. Measures should be taken to improve the availability of essential antibacterials and the affordability of originator brands.

Wafer scale fabrication of highly dense and uniform array of sub-5 nm nanogaps for surface enhanced Raman scatting substrates.

Metallic nanogap is very important for a verity of applications in plasmonics. Although several fabrication techniques have been proposed in the last decades, it is still a challenge to produce uniform nanogaps with a few nanometers gap distance and high throughput. Here we present a simple, yet robust method based on the atomic layer deposition (ALD) and lift-off technique for patterning ultranarrow nanogaps array. The ability to accurately control the thickness of the ALD spacer layer enables us to precisely define the gap size, down to sub-5 nm scale. Moreover, this new method allows to fabricate uniform nanogaps array along different directions densely arranged on the wafer-scale substrate. It is demonstrated that the fabricated array can be used as an excellent substrate for surface enhanced Raman scatting (SERS) measurements of molecules, even on flexible substrates. This uniform nanogaps array would also find its applications for the trace detection and biosensors.