Cancer survival statistics in China 2019-2021: a multicenter, population-based study.

Background: A milestone goal of the Healthy China Program (2019-2030) is to achieve 5-year cancer survival at 43.3% for all cancers combined by 2022. To assess the progress towards this target, we analyzed the updated survival for all cancers combined and 25 specific cancer types in China from 2019 to 2021. Methods: We conducted standardized data collection and quality control for cancer registries across 32 provincial-level regions in China, and included 6,410,940 newly diagnosed cancer patients from 281 cancer registries during 2008-2019, with follow-up data on vital status available until December 2021. We estimated the age-standardized 5-year relative survival overall and by site, age group, and period of diagnosis using the International Cancer Survival Standard Weights, and quantified the survival changes to assess the progress in cancer control. Results: In 2019-2021, the age-standardized 5-year relative survival for all cancers combined was 43.7% (95% confidence interval [CI], 43.6-43.7). The 5-year relative survival varied by cancer type, ranging from 8.5% (95% CI, 8.2-8.7) for pancreatic cancer to 92.9% (95% CI, 92.4-93.3) for thyroid cancer. Eight cancers had 5-year survival of over 60%, including cancers of the thyroid, breast, testis, bladder, prostate, kidney, uterus, and cervix. The 5-year relative survival was generally lower in males than in females. From 2008 to 2021, we observed significant survival improvements for cancers of the lung, prostate, bone, uterus, breast, cervix, nasopharynx, larynx, and bladder. The most significant improvement was in lung cancer. Conclusions: Progress in cancer control was evident in China. This highlights the importance of a comprehensive approach to control and prevent cancer.

The causal association between gut microbiota and postpartum depression: a two-sample Mendelian randomization study.

Background: An escalating body of clinical trials and observational studies hints at a plausible link between gut flora and postpartum depression (PPD). The definitive causal dynamics between these two entities remain shrouded in ambiguity. Therefore, in this study, we employed the two-sample Mendelian randomization approach to ascertain the causal link between gut microbiota and PPD. Methods: Summary-level GWAS data related to the human gut microbiota were obtained from the international consortium MiBioGen and the Dutch Microbiome Project (species). For PPD, GWAS data were derived from the FinnGen biobank, consisting 57,604 cases and 596,601 controls. The inverse variance weighted method (IVW) as the cornerstone of our analytical approach. Subsequent to this, a comprehensive suite of tests for pleiotropy and heterogeneity were conducted to ensure the reliability and robustness of our findings. Results: We identified 12 bacterial taxa associated with the risk of PPD. Veillonellaceae, Ruminococcaceae UCG 011, Bifidobacterium adolescentis, Paraprevotella clara, Clostridium leptum, Eubacterium siraeum, Coprococcus catus exhibited an inversely associated with the risk of PPD. Alphaproteobacteria, Roseburia, FamilyXIIIAD3011group, Alistipes onderdonkii, Bilophila wadsworthia showed a positive correlation with the risk of PPD. Limitations: The GWAS data derived from the MiBioGen consortium, DMP, and FinnGen consortium, may introduce selection bias. Moreover, the data primarily originates from European populations, hence extrapolating these results to diverse populations should be approached with caution. The etiological factors behind PPD remain enigmatic, alluding to the existence of potential undisclosed confounders. Conclusion: Based on this MR analysis, we found a causal relationship between certain gut microbial communities and PPD. Future clinical studies can further explore the treatment of PPD through the combined use of microorganisms. This not only offers insights into the pathogenesis of PPD but also lays the foundation for utilizing gut microbiota as biotherapeutics in treating neurological disorders.

SHP2 ablation mitigates osteoarthritic cartilage degeneration by promoting chondrocyte anabolism through SOX9.

Articular cartilage phenotypic homeostasis is crucial for life-long joint function, but the underlying cellular and molecular mechanisms governing chondrocyte stability remain poorly understood. Here, we show that the protein tyrosine phosphatase SHP2 is differentially expressed in articular cartilage (AC) and growth plate cartilage (GPC) and that it negatively regulates cell proliferation and cartilage phenotypic program. Postnatal SHP2 deletion in Prg4+ AC chondrocytes increased articular cellularity and thickness, whereas SHP2 deletion in Acan+ pan-chondrocytes caused excessive GPC chondrocyte proliferation and led to joint malformation post-puberty. These observations were verified in mice and in cultured chondrocytes following treatment with the SHP2 PROTAC inhibitor SHP2D26. Further mechanistic studies indicated that SHP2 negatively regulates SOX9 stability and transcriptional activity by influencing SOX9 phosphorylation and promoting its proteasome degradation. In contrast to published work, SHP2 ablation in chondrocytes did not impact IL-1-evoked inflammation responses, and SHP2's negative regulation of SOX9 could be curtailed by genetic or chemical SHP2 inhibition, suggesting that manipulating SHP2 signaling has translational potential for diseases of cartilage dyshomeostasis.

Dietary starch structure modulates nitrogen metabolism in laying hens via modifying glucose release rate.

The objective of this study was to investigate the effects of starch structure (Amylopectin/Amylose, AP/AM) in a low-protein diet on production performance, nitrogen utilization efficiency, and cecal flora in laying hens. Four hundred eighty 45-wk-age Hy-Line Gray laying hens were randomly allocated to five dietary groups and subjected to a 12-wk feeding trial. The AP/AM ratios of the five experiment diets were 1.0, 1.5, 2.0, 3.0, and 4.0. The results indicated that compared to other groups, laying hens fed with AP/AM 4.0 diets showed significantly improved average egg weight and feed conversion ratio (P < 0.05). Furthermore, as the AP/AM ratio increased, there was a significant linear enhancement in intestinal amino acids apparent digestibility, apparent metabolizable energy, and villus area (P < 0.05). Compared to the high AP groups, high-AM diets significantly increased eggshell thickness, crude protein digestibility, and reduced energy supply from amino acid oxidation in ileum (P < 0.05). Additionally, moderate-AM diets enriched with short-chain fatty acid-producing bacteria in the cecum, such as Lactobacillus, Rikenellaceae_RC9_gut_group, and Christensenellaceae_R-7_group, which are associated with the promoting nitrogen utilization. These findings may offer useful information on optimizing starch structure for the design of food products and relevant therapies due to the potential effects on nutrient metabolism and gut homeostasis.

Livestream sales prediction based on an interpretable deep-learning model.

Although live streaming is indispensable, live-streaming e-business requires accurate and timely sales-volume prediction to ensure a healthy supply-demand balance for companies. Practically, because various factors can significantly impact sales results, the development of a powerful, interpretable model is crucial for accurate sales prediction. In this study, we propose SaleNet, a deep-learning model designed for sales-volume prediction. Our model achieved correct prediction results on our private, real operating data. The mean absolute percentage error (MAPE) of our model's performance fell as low as 11.47% for a + 1.5-days forecast. Even for a 1-week forecast (+ 6 days), the MAPE was only 19.79%, meeting actual business needs and practical requirements. Notably, our model demonstrated robust interpretability, as evidenced by the feature contribution results which are consistent with prevailing research findings and industry expertise. Our findings provided a theoretical foundation for predicting shopping behavior in live-broadcast e-commerce and offered valuable insights for designing live-broadcast content and optimizing the user experience.

Advances in Nanotherapy for Targeting Senescent Cells.

Aging is an inevitable process in the human body, and cellular senescence refers to irreversible cell cycle arrest caused by external aging-promoting mechanisms. Moreover, as age increases, the accumulation of senescent cells limits both the health of the body and lifespan and even accelerates the occurrence and progression of age-related diseases. Therefore, it is crucial to delay the periodic irreversible arrest and continuous accumulation of senescent cells to address the issue of aging. The fundamental solution is targeted therapy focused on eliminating senescent cells or reducing the senescence-associated secretory phenotype. Over the past few decades, the remarkable development of nanomaterials has revolutionized clinical drug delivery pathways. Their unique optical, magnetic, and electrical properties effectively compensate for the shortcomings of traditional drugs, such as low stability and short half-life, thereby maximizing the bioavailability and minimizing the toxicity of drug delivery. This article provides an overview of how nanomedicine systems control drug release and achieve effective diagnosis. By presenting and analyzing recent advances in nanotherapy for targeting senescent cells, the underlying mechanisms of nanomedicine for senolytic and senomorphic therapy are clarified, providing great potential for targeting senescent cells.

Treatment of Neuropsychiatric Symptoms in Parkinson's Disease With Botulinum Toxin A: A 12 week Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: The study aimed to evaluate the impact of Botulinum toxin A (BoNT/A) on neuropsychiatric symptoms in Parkinson's disease (PD) patients. METHODS: A total of 125 PD patients and an equal number of age- and gender-matched healthy controls were involved. Mental health status was assessed using the Cornell Medical Index (CMI) self-assessment questionnaire. Sixty-four PD patients exhibiting neuropsychiatric symptoms were selected for the controlled study and randomly grouped into treatment and control groups. The treatment group received BoNT/A injections, while the control group received a placebo. The primary outcome measures included depression scores from the CMI and the proportion of patients displaying improvement in neuropsychiatric symptoms at 8 weeks post-treatment. The secondary outcome was other CMI scores at 4, 8, and 12 weeks post-treatment. RESULTS: The outcomes revealed that PD patients had significantly higher scores in various neuropsychiatric factors compared to healthy controls. At 4 weeks post-treatment, the treatment group displayed improvements in depression and tension. At 8 weeks post-treatment, they exhibited significant reductions in depression, anxiety, sensitivity, and tension compared to the control group. Moreover, a notably higher percentage of patients in the treatment group showed improvement in neuropsychiatric symptoms compared to the control group. At 12 weeks post-treatment, the treatment group exhibited significant improvements in somatization, depression, sensitivity, and tension. CONCLUSION: PD patients commonly experience multiple neuropsychiatric symptoms, and BoNT/A has demonstrated efficacy in alleviating these symptoms. Specifically, BoNT/A was found to effectively alleviate somatization, tension, anxiety, depression, and sensitivity in PD patients.

Collaborative augmented reconstruction of 3D neuron morphology in mouse and human brains.

Digital reconstruction of the intricate 3D morphology of individual neurons from microscopic images is a crucial challenge in both individual laboratories and large-scale projects focusing on cell types and brain anatomy. This task often fails in both conventional manual reconstruction and state-of-the-art artificial intelligence (AI)-based automatic reconstruction algorithms. It is also challenging to organize multiple neuroanatomists to generate and cross-validate biologically relevant and mutually agreed upon reconstructions in large-scale data production. Based on collaborative group intelligence augmented by AI, we developed a collaborative augmented reconstruction (CAR) platform for neuron reconstruction at scale. This platform allows for immersive interaction and efficient collaborative editing of neuron anatomy using a variety of devices, such as desktop workstations, virtual reality headsets and mobile phones, enabling users to contribute anytime and anywhere and to take advantage of several AI-based automation tools. We tested CAR's applicability for challenging mouse and human neurons toward scaled and faithful data production.

Efficacy and safety of hepatic arterial infusion chemotherapy combined with fruquintinib and tislelizumab for patients with microsatellite stable colorectal cancer liver metastasis following failure of multiple-line therapy.

Background and aim: The prognosis of microsatellite stable (MSS)-colorectal cancer liver metastasis (CRCLM) following failure of multi-line therapy remains dismal. The aim of this study is to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) plus fruquintinib and tislelizumab (HAIC-F-T treatment) for MSS-CRCLM which failed from multiple-line therapy. Methods: From February 2021 to June 2023, 45 patients with MSS-CRCLM after failure of multiple-line therapy who received HAIC combined with fruquintinib and tislelizumab (HAIC-F-T triple treatment) were enrolled. The combination therapy included HAIC regimens with oxaliplatin and 5-fluorouracil or irinotecan, oxaliplatin, and 5-fluorouracil on days 1-2, intravenous tislelizumab (200 mg) before HAIC on day 1, and oral fruquintinb (3 mg/d) on day 3-21, every 4 weeks. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Results: The follow-up ended on June 22, 2024, with a median follow-up time of 17.5 months. The objective response rate was 42.2%, and the disease control rate was 82.2%. The median OS was 15.3 months (95% confidence interval [CI]:12.634-17.966), and the median PFS was 7.5 months (95% CI:5.318-9.682). The independent risk factors related to worse OS were previous PD-1 immunotherapy (P = 0.021) and the number of HAIC-F-T triple treatment cycles of ≤ 2 (P = 0.007). The incidence of grade 3 or higher adverse events (AEs) was 20%, with the most frequent grade 3 or higher AEs being abdominal pain (3/45, 6.7%). Conclusion: HAIC combined with fruquintinib and tislelizumab may be an alternative salvage treatment for patients with MSS-CRCLM following failure of multiple-line therapy.

A dual-mode composite nanozyme-based cascade colorimetric-fluorescence aptasensor for Salmonella Typhimurium detection.

BACKGROUND: Salmonella Typhimurium poses a serious threat to human health worldwide, necessitating the development of a rapid, sensitive, and convenient method for S. Typhimurium detection. Nanozymes are considered ideal signal report elements, which are extensively used for developing colorimetric methods. However, single-component nanozymes display low catalytic activity, and colorimetric methods are susceptible to environmental interference, reducing the sensitivity and accuracy of detection results. To address these drawbacks, this study constructed a dual-mode composite nanozyme-based cascade colorimetric-fluorescence aptasensor for S. Typhimurium detection in food. RESULTS: In this study, the composite Fe3O4@MIL-100(Fe) nanozymes were successful synthesized and demonstrated substantial peroxide-like activity, with 4.76-fold higher specificity activity (SA) than that of Fe3O4 nanozymes. Then, a glucose oxidase (GOx)-Fe3O4@MIL-100(Fe) cascade reaction was developed for colorimetric detection via an aptamer to facilitate the formation of Fe3O4@MIL-100(Fe)/S. Typhimurium/carboxylated g-C3N4 (CCN)-GOx sandwich complexes. Meanwhile, the fluorescence mode was achieved by measuring the fluorescence intensity of the sandwich complexes. In optimum conditions, the dual-mode detection limits (LOD) were 1.8 CFU/mL (colorimetric mode) and 1.2 CFU/mL (fluorescence mode), respectively, with the S. Typhimurium concentration ranging from 10 CFU/mL to 107 CFU/mL. Finally, the feasibility of the dual-mode colorimetric-fluorescence method was validated via three actual samples, yielding recovery rates of 77.32 % to91.17 % and 82.17 % to 103.7 %, respectively. SIGNIFICANCE AND NOVELTY: This study successfully develops a composite nanozyme-based cascade colorimetric and fluorescence dual-mode aptasensor for S. Typhimurium detection. It presents several distinct benefits, such as a broader linear range (10-107 CFU/mL), a lower LOD value (1.2 CFU/mL), and more accurate results. More importantly, the proposed dual-mode method displays a low LOD in colorimetric mode, demonstrating considerable potential for S. Typhimurium on-site detection in food.

Liraglutide alleviates sepsis-induced acute lung injury by regulating pulmonary surfactant through inhibiting autophagy.

BACKGROUND: Pulmonary surfactant (PS) plays an important role in the treatment of sepsis-induced acute lung injury (ALI). Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, improves the secretion and function of PS in ALI, but the underlying mechanism remains unknown. This study aimed to investigate how liraglutide regulates PS secretion in ALI. METHODS: C57BL/6 mice were injected subcutaneously with normal saline containing different concentrations of liraglutide after the establishment of the ALI model. MLE-12 cells were treated with liraglutide after LPS stimulation. The survival rate of mice, wet/dry weight ratio, inflammatory factors in bronchoalveolar lavage fluid (BALF), pulmonary injury, and apoptosis were analyzed. Cell viability, proliferation, apoptosis, the expression of SP-A, SP-B, and expression of autophagy-related proteins in cells were measured. RESULTS: ALI mice showed reduced pulmonary injury, less apoptosis, and less inflammation compared to the controls. Liraglutide prolonged survival, decreased the wet/dry weight ratio, reduced inflammatory responses, and attenuated pulmonary edema compared with the ALI group. Moreover, LPS-induced cell damage and reduction of SP-A and SP-B expression were markedly reversed by liraglutide in MLE-12 cells. Furthermore, the protective effects of liraglutide were reversed by rapamycin. CONCLUSION: Liraglutide alleviate sepsis-induced ALI by inhibiting autophagy and regulating PS.

Complete mitochondrial genome and phylogenetic analysis of Mancinella alouina.

BACKGROUND: The Muricidae family in the Class Gastropoda comprises numerous species with a vast range of morphological features and a worldwide presence. The phylogeny of the Muricidae has been analyzed in previous studies; however, the evolutionary relationships among the main branches of the Muricidae remain unknown. METHODS AND RESULTS: In the present study, the mitochondrial genome of Mancinella alouina was sequenced. The mitochondrial genome was found to be 16,671 bp in length and made up of 37 genes (13 protein-coding genes, 22 transfer RNA and 2 ribosomal RNA genes). The genome has an A-T-rich region (66.5% A + T content) and all of the PCGs use the ATN start codon and the TAG or TAA stop codons. The mitochondrial gene arrangement of Mancinella alouina is similar to that of other Muricidae, except for Ocinebrellus inornatus and Ceratostoma burnetti. On the basis of a flexible molecular clock model, time-calibrated phylogenetic results indicate that the genus Mancinella diverged roughly 18.09 Mya, and that the family Muricidae emerged in the Late Cretaceous. CONCLUSIONS: This study reveals the structural and sequence information features of the mitochondrial genome of Mancinella alouina. This study provides evidence for the relationships within the family Muricidae at the molecular level, and infer the divergence time. The results of phylogenetic analyses strongly support the current classification.

Non-linear association of triglyceride-glucose index with cardiovascular and all-cause mortality in T2DM patients with diabetic kidney disease: NHANES 2001-2018 retrospective cohort study.

BACKGROUND: The triglyceride glucose (TyG) index is a cutting-edge and highly effective marker of insulin resistance, a crucial factor in the development and exacerbation of diabetic kidney disease (DKD). To date, there has been limited research on how the triglyceride-glucose (TyG) index affects the outlook for patients suffering from DKD. METHODS: In this multicenter retrospective cohort study, the analysis recruited 2,203 DKD patients from the National Health and Nutrition Examination Survey (NHANES) dataset, which covers the US from 2001 to 2018. The research applied a Cox proportional hazards model with multiple variables to investigate the association of the TyG index with mortality outcomes. Restricted cubic splines (RCS) and methods for analyzing threshold effects were employed to identify possible non-linear relationships. RESULTS: Over nearly 19 years of follow-up, this study captured data on 753 all-cause and 231 cardiovascular disease-specific fatalities. Sophisticated statistical methods, including RCS and smoothing curve adjustments via penalized splines, helped identify distinctive patterns: The baseline TyG index was observed to have a U-shaped pattern related to overall mortality and an L-shape with cardiovascular diseases(CVD) mortality among individuals with DKD. Notably, TyG index below 9.15 for overall mortality and 9.27 for CVD mortality were linked to reduced death rates (HR = 0.65, 95% CI = 0.52-0.82 for all-cause; HR = 0.58, 95% CI = 0.43-0.83 for CVD). On the other hand, TyG index exceeding these benchmarks (greater than 9.15 for all-cause and 9.27 for CVD) correlated with increased all-cause mortality risks (HR = 1.21, 95% CI = 1.02-1.43) and showed a non-significant change in CVD mortality risks (HR = 1.07, 95% CI = 0.83-1.38). CONCLUSIONS: This study emphasizes the non-linear linkage involving the TyG index and death rates due to CVD and other factors in patients with DKD, demonstrating its effectiveness in estimating potential adverse events within this demographic.

Evolution of Esophageal Cancer Incidence Patterns in Hong Kong, 1992-2021: An Age-Period-Cohort and Decomposition Analysis.

Objective: To elucidate the historical trends, underlying causes and future projections of esophageal cancer incidence in Hong Kong. Methods: Utilizing the Age-Period-Cohort (APC) model, we analyzed data from the Hong Kong Cancer Registry (1992-2021) and United Nations World Population Prospects 2022 Revision. Age-standardized incidence rates were computed, and APC models evaluated age, period, and cohort effects. Bayesian APC modeling, coupled with decomposition analysis, projected future trends and identified factors influencing incidence. Results: Between 1992 and 2021, both crude and age-standardized incidence rates of esophageal cancer witnessed significant declines. Net drifts exhibited pronounced downward trends for both sexes, with local drift diminishing across all age groups. Period and cohort rate ratios displayed a consistent monotonic decline for both sexes. Projections indicate a continued decline in esophageal cancer incidence. Population decomposition analysis revealed that epidemiological changes offset the increase in esophageal cancer cases due to population growth and aging. Conclusion: The declining trend of esophageal cancer in Hong Kong is influenced by a combination of age, period, and cohort. Sustaining and enhancing these positive trends requires continuous efforts in public health interventions.

The Association Between Prolactin Levels and Cognitive Function in Female Patients With Severe Mental Disorders.

OBJECTIVE: Cognition impairments are considered as a fundamental characteristic of severe mental disorders (SMD). Recent studies suggest that hyperprolactinemia may exert a detrimental influence on cognitive performance in patients with SMD. The objective of this study was to investigate the correlation between serum prolactin levels and cognitive function in female individuals diagnosed with SMD. METHODS: We conducted a study on 294 patients with SMD and 195 healthy controls, aged between 14 to 55 years old. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), while prolactin levels were measured in serum. Descriptive analysis and comparative analysis were performed to compare cognitive function and prolactin levels between groups, and linear regression models were used to explore the relationship between prolactin and cognitive function. RESULTS: Compared to the healthy control, individuals with SMD exhibited significantly higher levels of prolactin, while scoring lower on RBANS total and every index scores. Furthermore, a negative association between prolactin levels and cognitive function (RBANS total index score, attention, and delayed memory) was observed in SMD patients. Importantly, this inverse correlation between prolactin and cognition function (RBANS total index score, total scale score, and attention) persisted in patients who were not taking medications that could potentially influence serum prolactin levels. CONCLUSION: Our study reveals a significant correlation between elevated prolactin levels and cognitive impairment in female patients with SMD, underscoring the importance of monitoring prolactin levels in order to prevent cognitive deterioration among female SMD patients.

Identification of a Predictive Model for Schizophrenia Based on SNPs in a Chinese Population.

Background: Schizophrenia is a devastating mental disease with high heritability. A growing number of susceptibility genes associated with schizophrenia, as well as their corresponding SNPs loci, have been revealed by genome-wide association studies. However, using SNPs as predictors of disease and diagnosis remains difficult. Here, we aimed to uncover susceptibility SNPs in a Chinese population and to construct a prediction model for schizophrenia. Methods: A total of 210 participants, including 70 patients with schizophrenia, 70 patients with bipolar disorder, and 70 healthy controls, were enrolled in this study. We estimated 14 SNPs using published risk loci of schizophrenia, and used these SNPs to build a model for predicting schizophrenia via comparison of genotype frequencies and regression. We evaluated the efficacy of the diagnostic model in schizophrenia and control patients using ROC curves and then used the 70 patients with bipolar disorder to evaluate the model's differential diagnostic efficacy. Results: 5 SNPs were selected to construct the model: rs148415900, rs71428218, rs4666990, rs112222723 and rs1716180. Correlation analysis results suggested that, compared with the risk SNP of 0, the risk SNP of 3 was associated with an increased risk of schizophrenia (OR = 13.00, 95% CI: 2.35-71.84, p = 0.003). The ROC-AUC of this prediction model for schizophrenia was 0.719 (95% CI: 0.634-0.804), with the greatest sensitivity and specificity being 60% and 80%, respectively. The ROC-AUC of the model in distinguishing between schizophrenia and bipolar disorder was 0.591 (95% CI: 0.497-0.686), with the greatest sensitivity and specificity being 60% and 55.7%, respectively. Conclusion: The SNP risk score prediction model had good performance in predicting schizophrenia. To the best of our knowledge, previous studies have not applied SNP-based models to differentiate between cases of schizophrenia and other mental illnesses. It could have several potential clinical applications, including shaping disease diagnosis, treatment, and outcomes.

Bispecific CAR-T cells targeting CD19/20 in patients with relapsed or refractory B cell non-Hodgkin lymphoma: a phase I/II trial.

Non-Hodgkin lymphoma (NHL) is a common malignancy in the hematologic system, and traditional therapy has limited efficacy for people with recurrent/refractory NHL (R/R NHL), especially for patients with diffuse large B cell lymphoma (DLBCL). Chimeric antigen receptor (CAR) T-cell therapy is a novel and effective immunotherapy strategy for R/R hematopoietic malignancies, but relapses can occur due to the loss of CAR-T cells in vivo or the loss of antigen. One strategy to avoid antigen loss after CAR-T cell therapy is to target one more antigen simultaneously. Tandem CAR targeting CD19 and CD22 has demonstrated the reliability of tandem CAR-T cell therapy for R/R B-ALL. This study explores the therapeutic potential of tandem CD19/20 CAR-T in the treatment of R/R B cell NHL. The efficacy and safety of autologous CD19/20 CAR-T cells in eleven R/R B cell NHL adult patients were evaluated in an open-label, single-arm trial. Most patients achieved complete response, exhibiting the efficacy and safety of tandem CD19/20 CAR-T cells. The TCR repertoire diversity of CAR-T cells decreased after infusion. The expanded TCR clones in vivo were mainly derived from TCR clones that had increased expression of genes associated with immune-related signaling pathways from the infusion product (IP). The kinetics of CAR-T cells in vivo were linked to an increase in the expression of genes related to immune response and cytolysis/cytotoxicity.

Global research trends on melasma: a bibliometric and visualized study from 2014 to 2023.

Melasma, a prevalent pigmentary disorder, is characterized by its complex etiology, propensity for recurrence, and resistance to treatment. However, there is currently no research on melasma through bibliometrics and visualisation. This study analyses the hotspots and trends in the field based on 2,709 publications from the Web of Science Core Collection (WOSCC). We carried out bibliometric analyses using Citespace software for different countries/regions, institutions, authors, and keywords. References were also analysed using VoSviewer. The results indicate that overall, there has been an increase in publications related to melasma since 2014. According to the analysis of the collaborative network diagram, the United States, Egyptian Knowledge Bank, and Benjakul Soottawat are the most contributing countries, institutions, and authors, respectively. Reference and keyword analyses have identified the pathogenesis and treatment of melasma as a prevalent topic in recent years. And how to find new treatment options and more effective therapeutic drugs is a future research trend. This is the first bibliometric and visual analysis of melasma-related literature to explore research hotspots and trends.

High brightness terahertz quantum cascade laser with near-diffraction-limited Gaussian beam.

High-power terahertz (THz) quantum cascade laser, as an emerging THz solid-state radiation source, is attracting attention for numerous applications including medicine, sensing, and communication. However, due to the sub-wavelength confinement of the waveguide structure, direct beam brightness upscaling with device area remains elusive due to several mode competition and external optical lens is normally used to enhance the THz beam brightness. Here, we propose a metallic THz photonic crystal resonator with a phase-engineered design for single mode surface emission over a broad area. The quantum cascade surface-emitting laser is capable of delivering an output peak power over 185 mW with a narrow beam divergence of 4.4° × 4.4° at 3.88 THz. A high beam brightness of 1.6 × 107 W sr-1m-2 with near-diffraction-limited M2 factors of 1.4 in both vertical and lateral directions is achieved from a large device area of 1.6 × 1.6 mm2 without using any optical lenses. The adjustable phase shift between the lattices enables a stable and high-intensity surface emission over a broad device area, which makes it an ideal light extractor for large-scale THz emitters. Our research paves the way to high brightness solid-state THz lasers and facilitates new applications in standoff THz imaging, detection, and diagnosis.

Traceable Optical Physical Unclonable Functions Based on Germanium Vacancy in Diamonds.

Physical unclonable functions (PUFs) have emerged as an unprecedented solution for modern information security and anticounterfeiting by virtue of their inherent unclonable nature derived from distinctive, randomly generated physical patterns that defy replication. However, the creation of traceable optical PUF tags remains a formidable challenge. Here, we demonstrate a traceable PUF system whose unclonability arises from the random distribution of diamonds and the random intensity of the narrow emission from germanium vacancies (GeV) within the diamonds. Tamper-resistant PUF labels can be manufactured on diverse and intricate structural surfaces by blending diamond particles into polydimethylsiloxane (PDMS) and strategically depositing them onto the surface of objects. The resulting PUF codes exhibit essentially perfect uniformity, uniqueness, reproducibility, and substantial encoding capacity, making them applicable as a private key to fulfill the customization demands of circulating commodities. Through integration of a digitized "challenge-response" protocol, a traceable and highly secure PUF system can be established, which is seamlessly compatible with contemporary digital information technology. Thus, the GeV-PUF system holds significant promise for applications in data security and blockchain anticounterfeiting, providing robust and adaptive solutions to address the dynamic demands of these domains.