Immune checkpoint blockade (ICB) targeting PD-1/PD-L1 has been used for the treatment of head and neck squamous cell carcinoma (HNSCC). However, the overall response rate to ICB therapy for HNSCC ...remains less than 20%. It has recently been reported that the appearance of tertiary lymphoid structures (TLSs) in tumor tissue is correlated with better prognosis and response to ICB treatment. Here, we demonstrated an immune classification for the tumor microenvironment (TME) of HNSCC by analyzing The Cancer Genome Atlas (TCGA)–HNSCC data set and found that immunotype D with TLS enrichment had a better prognosis and response to ICB treatment. Furthermore, we observed that TLSs were present in a part of tumor samples of human papillomavirus (HPV) infection negative HNSCC (HPV− HNSCC) and were associated with the densities of dendritic cell (DC)–LAMP+ DCs, CD4+ T cells, CD8+ T cells, and progenitor T cells in TME. We established an HPV− HNSCC mouse model with TLS-enriched TME by overexpressing LIGHT in a mouse HNSCC cell line. We found that the induction of TLS formation enhanced the response to PD-1 blockade treatment in the HPV− HNSCC mouse model, accompanied by increases in DCs and progenitor exhausted CD8+ T cells in the TME. Elimination of CD20+ B cells attenuated the therapeutic effect of PD-1 pathway blockade in TLS+ HPV− HNSCC mouse models. These results indicate that TLSs contribute to the favorable prognosis and antitumor immunity of HPV− HNSCC. Inducing TLS formation in HPV− HNSCC tumors is a potential therapeutic method for improving the ICB response rate in patients with HPV− HNSCC.
Three-dimensional (3D) topological Dirac semimetals (TDSs) represent an unusual state of quantum matter that can be viewed as "3D graphene." In contrast to 2D Dirac fermions in graphene or on the ...surface of 3D topological insulators, TDSs possess 3D Dirac fermions in the bulk. By investigating the electronic structure of Na3Bi with angle-resolved photoemission spectroscopy, we detected 3D Dirac fermions with linear dispersions along all momentum directions. Furthermore, we demonstrated the robustness of 3D Dirac fermions in Na3Bi against in situ surface doping. Our results establish Na3Bi as a model system for 3D TDSs, which can serve as an ideal platform for the systematic study of quantum phase transitions between rich topological quantum states.
This book is a comprehensive and intensive monograph for scientists, engineers and applied mathematicians, as well as graduate students in fluid dynamics. It starts with a brief review of ...fundamentals of fluid dynamics, with an innovative emphasis on the intrinsic orthogonal decomposition of fluid dynamics process. This is followed by vortex dynamics dealing with the motion, interaction, stability, and breakdown of various vortices. Typical vortex structures are analyzed in laminar, translational, and turbulent flows, including stratified and rotational fluids. In another chapter vortical flow management is presented, such as diagnostics and control. Physical understanding of vortical flow phenomena and mechanisms is the first priority throughout the book. To make the book self-contained, some mathematical background is briefly presented in the main text, but major prerequisites are systematically given in appendices.
Three-dimensional (3D) topological Dirac semimetals (TDSs) are a recently proposed state of quantum matter that have attracted increasing attention in physics and materials science. A 3D TDS is not ...only a bulk analogue of graphene; it also exhibits non-trivial topology in its electronic structure that shares similarities with topological insulators. Moreover, a TDS can potentially be driven into other exotic phases (such as Weyl semimetals, axion insulators and topological superconductors), making it a unique parent compound for the study of these states and the phase transitions between them. Here, by performing angle-resolved photoemission spectroscopy, we directly observe a pair of 3D Dirac fermions in Cd3As2, proving that it is a model 3D TDS. Compared with other 3D TDSs, for example, β-cristobalite BiO2 (ref. 3) and Na3Bi (refs 4, 5), Cd3As2 is stable and has much higher Fermi velocities. Furthermore, by in situ doping we have been able to tune its Fermi energy, making it a flexible platform for exploring exotic physical phenomena.
Objective
To assess the current prevalence of and risk factors for infertility among couples of reproductive age in China.
Design
Population‐based cross‐sectional study.
Setting
We approached 25 270 ...couples in eight provinces/municipalities, of whom 18 571 (response rate 74%) were interviewed.
Population
Couples living together and married for more than 1 year, of whom the female spouse was 20–49 years old.
Methods
Women were approached via telephone and face‐to‐face conversation to complete the standardised and structured questionnaire by trained interviewers.
Main outcome measures
Prevalence of and risk factors for infertility.
Results
Among women ‘at risk’ of pregnancy, the prevalence of infertility was 15.5% (2680/17 275). Among 10 742 women attempting to become pregnant, the prevalence of infertility was 25.0% (2680/10 742), which increased with age in the second population. Among women who failed to achieve pregnancy in the last 12 months, 3470 finished our questionnaire about fertility care, and 55.2% (1915/3470) of them had sought medical help. Sociodemographic risk factors for infertility included lower educational level adjusted odds ratio (aOR) 3.4, 95% CI 2.0–5.5 and employment (aOR 2.3, 95% CI 1.9–2.9). Clinical risk factors were irregular menstrual cycle (aOR 1.8, 95% CI 1.2–2.5), light menstrual blood volume (aOR 1.6, 95% CI 1.2–2.0), history of cervicitis (aOR 1.5, 95% CI 1.2–2.0) and endometriosis (aOR 3.1, 95% CI 1.1–9.3), previous stillbirth (aOR 2.1, 95% CI 1.3–3.3) and miscarriage (aOR 2.7, 95% CI 2.1–3.5). In addition, history of operation was a significant risk factor of infertility.
Conclusions
Among couples of reproductive age in China, the prevalence of infertility was 25%, and almost half of the couples experiencing infertility had not sought medical help.
Tweetable
In China, 25% of couples actively attempting to become pregnant suffered infertility.
Tweetable
In China, 25% of couples actively attempting to become pregnant suffered infertility.
The plastic deformation behavior and the effects of the impact time on the LY2 aluminum (Al) alloy during multiple laser shock processing (LSP) impacts were investigated. The residual stress in the ...near-surface region was determined by X-ray diffraction. In addition, the micro-structural features of the hardening layer were characterized by scanning electron microscopy, optical microscopy and transmission electron microscopy. It was found that the micro-structure was obviously refined due to the ultra-high plastic strain induced by multiple LSP impacts. The minimum grain size in the top surface after multiple LSP impacts was about 100–200
nm. The grain refinement process after multiple LSP impacts can be described as follows: (i) the formation and development of dislocation lines in original grains; (ii) dislocation tangles (DTs) and the formation of dense dislocation walls (DDWs); (iii) transformation of DTs and DDWs into subgrain boundaries; and (iv) evolution of the continuous dynamic recrystallization in subgrain boundaries to refined grain boundaries.
Summary
Background
Inflammation plays a vital role in liver cirrhosis progression and prognosis.
Aim
To investigate the prognostic significance of inflammatory response markers in decompensated ...cirrhotic patients without acute‐on‐chronic liver failure (ACLF).
Methods
Independent predictors were identified using multivariate Cox model and then assembled into a nomogram to predict survival. Concordance index (C‐index) and time‐dependent receiver operating characteristics (td‐ROC) analysis were adopted to evaluate and compare the performance of nomogram, model for end‐stage liver disease (MELD) scores, MELD‐Na and Chronic Liver Failure‐consortium score for acute decompensated (CLIF‐C ADs).
Results
A total of 902 decompensated cirrhotic patients with different aetiologies were enrolled, with 6‐month, 1‐year and 3‐year mortality of 18.6%, 24.4% and 34.8%, respectively. The cut‐off values for neutrophil‐to‐lymphocyte ratio (NLR) and lymphocyte‐to‐monocyte ratio (LMR) determined by X‐tile program were 5.7 and 1.1 respectively. Patients with NLR>5.7 or LMR≤1.1 had significantly higher mortality (P < 0.001). Independent factors derived from multivariable Cox analysis of development cohort to predict mortality were age, NLR and LMR (hazard ratio (HR): 1.064, 95% confidence interval (CI): 1.045–1.084, P < 0.001; HR: 1.124, 95%CI: 1.091–1.158, P < 0.001; HR: 0.794, 95%CI: 0.702–0.898, P < 0.001, respectively). The C‐indexes of nomogram were higher than that of MELD score, MELD‐Na and CLIF‐C ADs for predicting survival. The tdROC and decision curves showed that nomogram was superior to MELD score, MELD‐Na and CLIF‐C ADs. Similar results were observed in validation cohort.
Conclusion
The proposed nomogram with neutrophil‐to‐lymphocyte ratio and lymphocyte‐to‐monocyte ratio resulted in accurate prognostic prediction for decompensated cirrhotic patients without ACLF.
Linked ContentThis article is linked to Forest and Cai and Shi et al papers. To view these articles visit https://doi.org/10.1111/apt.14183 and https://doi.org/10.1111/apt.14208.
Besides the cusp, polar cap, and auroral oval, the nightside subauroral zone has also recently been reported as a source region of the ionospheric oxygen outflows. However, the detailed mass and ...energy sources of these ions remain open questions. Here, we address this issue from the perspective of the response of conjugate hemispheres. Investigation of Van Allen Probes data demonstrates a notable preference of oxygen outflows from the nightside subauroral zone from the sunlit hemisphere. This characteristic eliminates the possibility of nightside auroral precipitation playing a significant role, as it is more prominent in darkness. Instead, it highlights sunlight‐induced ionization as the mass source and enhanced plasma waves from the magnetotail as the energy source. The results presented here further support the nightside subauroral zone as an independent source of magnetospheric oxygen ions.
Plain Language Summary
Single‐charged oxygen ions, believed to ultimately originate from the ionosphere, are the main carriers of the ring current during severe space weather, including super geomagnetic storms and substorms. Therefore, comprehending where and how they come from is crucial for understanding the magnetosphere and space weather. Recent studies have reported the nightside subauroral zone as a source region, besides the usually cited cusp, polar cap, and auroral oval. However, the detailed mechanisms for the subauroral oxygen outflows remain open questions. In this study, we address this issue by studying how opposite hemispheres react simultaneously in subauroral oxygen outflow events observed by the Van Allen Probes. Data analysis reveals that these outflows tend to occur in the local summer hemisphere, where the nightside subauroral ionosphere receives more sunlight compared to the opposite hemisphere. This feature rules out nightside auroral precipitation playing a significant role, as it is more noticeable in the dark. Instead, it points to sunlight‐induced ionization as the source of mass and enhanced plasma waves from the magnetotail as the source of energy. Our findings reinforce the idea that the nightside subauroral zone is an important source of ionospheric oxygen outflows.
Key Points
The Van Allen Probes have observed oxygen outflows from the nightside subauroral ionosphere in a single hemisphere
Statistics reveal a preference for the outflows in sunlit hemisphere, distinguishing them from auroral outflows more prominent in darkness
This preference highlights sunlight‐induced ionization and waves from the magnetotail as the source of mass and energy
It has long been known that males are more susceptible than females to hepatocellular carcinoma (HCC), but the reason remains elusive. In this study, we investigated the expression and function of ...the long noncoding RNA FTX (lnc-FTX), an X-inactive-specific transcript (XIST) regulator transcribed from the X chromosome inactivation center, in both HCC and HCC gender disparity. lnc-FTX is expressed at higher levels in female livers than in male livers and is significantly downregulated in HCC tissues compared with normal liver tissues. Patients with higher lnc-FTX expression exhibited longer survival, suggesting that lnc-FTX is a useful prognostic factor for HCC patients. lnc-FTX inhibits HCC cell growth and metastasis both in vitro and in vivo. Mechanistically, lnc-FTX represses Wnt/β-catenin signaling activity by competitively sponging miR-374a and inhibits HCC cell epithelial-mesenchymal transition and invasion. In addition, lnc-FTX binds to the DNA replication licensing factor MCM2, thereby impeding DNA replication and inhibiting proliferation in HCC cells. In conclusion, these findings suggest that lnc-FTX may act as a tumor suppressor in HCC through physically binding miR-374a and MCM2. It may also be one of the reasons for HCC gender disparity and may potentially contribute to HCC treatment.
The molecular mechanism underlying gastric cancer (GC) invasion and metastasis is still poorly understood. In this study, we tried to investigate the roles of CXCR4 and CXCR2 signalings in gastric ...cancer metastasis. A highly invasive gastric cancer cell model was established. Chemokines receptors were profiled to search for the accountable ones. Then the underlying molecular mechanism was investigated using both in vitro and in vivo techniques, and the clinical relevance of CXCR4 and CXCR2 expression was studied in gastric cancer samples. CXCR4 and CXCR2 were highly expressed in a high invasive gastric cancer cell model and in gastric cancer tissues. Overexpression of CXCR4 and CXCR2 was associated with more advanced tumor stage and poorer survival for GC patients. CXCR4 and CXCR2 expression strongly correlated with each other in the way that CXCR2 expression changed accordingly with the activity of CXCR4 signaling and CXCR4 expression also changed in agreement with CXCR2 activity. Further studies demonstrated CXCR4 and CXCR2 can both activated NF-κB and STAT3 signaling, while NF-κBp65 can then transcriptionally activate CXCR4 and STAT3 can activate CXCR2 expression. This crosstalk between CXCR4 and CXCR2 contributed to EMT, migration and invasion of gastric cancer. Finally, Co-inhibition of CXCR4 and CXCR2 is more effective in reducing gastric cancer metastasis. Our results demonstrated that CXCR4 and CXCR2 cross-activate each other to promote the metastasis of gastric cancer.
PDF
