Colorectal cancer subtyping and immune landscape analysis based on natural killer cell-related genes.

BACKGROUND AND STUDY AIMS: The prognosis of colorectal cancer (CRC) is related to natural killer (NK) cells, but the molecular subtype features of CRC based on NK cells are still unknown. This study aimed to identify NK cell-related molecular subtypes of CRC and analyze the survival status and immune landscape of patients with different subtypes. PATIENTS/MATERIAL AND METHODS: mRNA expression data, single nucleotide variant (SNV) data, and clinical information of CRC patients were obtained from The Cancer Genome Atlas. Differentially expressed genes (DEGs) were obtained through differential analysis, and the intersection was taken with NK cell-associated genes to obtain 103 NK cell-associated CRC DEGs (NCDEGs). Based on NCDEGs, CRC samples were divided into three clusters through unsupervised clustering analysis. Survival analysis, immune analysis, Gene Set Enrichment Analysis (GSEA), and tumor mutation burden (TMB) analysis were performed. Finally, NCDEG-related small-molecule drugs were screened using the CMap database. RESULTS: Survival analysis revealed that cluster2 had a lower survival rate than cluster1 and cluster3 (p < 0.05). Immune infiltration analysis found that the immune infiltration levels and immune checkpoint expression levels of cluster1_3 were substantially higher than those of cluster2, and the tumor purity was the opposite (p < 0.05). GSEA presented that cluster1_3 was significantly enriched in the chemokine signaling pathway, ECM receptor interaction, and antigen processing and presentation pathways (p < 0.05). The TMB of cluster1_3 was significantly higher than that of cluster2 (p < 0.05). Genes with the highest mutation rate in CRC were APC, TP53, TTN, and KRAS. Drug prediction results showed that small-molecule drugs that reverse the upregulation of NCDEGs, deoxycholic acid, dipivefrine, phenformin, and other drugs may improve the prognosis of CRC. CONCLUSION: NK cell-associated CRC subtypes can be used to evaluate the tumor characteristics of CRC patients and provide an important reference for CRC patients.

Integrated molybdenum single atom array sensors with multichannels for nitrite detection in foods.

Nitrite (NO2-) is present in a variety of foods, but the excessive intake of NO2- can indirectly lead to carcinogenic, teratogenic, mutagenicity and other risks to the human body. Therefore, the detection of NO2- is crucial for maintaining human health. In this study, an integrated array sensor for NO2- detection is developed based on molybdenum single atom material (IMSMo-SAC) using high-resolution electrohydrodynamic (EHD) printing technology. The sensor comprises three components: a printed electrode array, multichannels designed on polydimethylsiloxane (PDMS) and an electronic signal process device with bluetooth. By utilizing Mo-SAC to facilitate electron transfer during the redox reaction, rapid and efficient detection of NO2- can be achieved. The sensor has a wide linear range of 0.1 µM-107.8 mM, a low detection limit of 33 nM and a high sensitivity of 0.637 mA-1mM-1 cm-2. Furthermore, employing this portable array sensor allows simultaneously measurements of NO2- concentrations in six different foods samples with acceptable recovery rates. This array sensor holds great potential for detecting of small molecules in various fields.

Deletion of Impdh2 in adipocyte precursors limits the expansion of white adipose tissue and enhances metabolic health with overnutrition.

The equilibrium between the hypertrophic growth of existing adipocytes and adipogenesis is vital in managing metabolic stability in white adipocytes when faced with overnutrition. Adipogenesis has been established as a key player in combating metabolic irregularities caused by various factors. However, the benefits of increasing adipogenesis-mediated white adipose tissue (WAT) expansion for metabolic health regulation remain uncertain. Our findings reveal an increase in Impdh2 expression during the adipogenesis phase, both in vivo and in vitro. Xmp enhances adipogenic potential by fostering mitotic clonal expansion (MCE). The conditional knockout of Impdh2 in adipocyte progenitor cells(APCs) in adult and aged mice effectively curbs white adipose tissue expansion, ameliorates glucose tolerance, and augments energy expenditure under high-fat diet (HFD). However, no significant difference is observed under normal chow diet (NCD). Concurrently, the knockout of Impdh2 in APCs significantly reduces the count of new adipocytes induced by HFD, without affecting adipocyte size. Mechanistically, Impdh2 regulates the proliferation of APCs during the MCE phase via Xmp. Exogenous Xmp can significantly offset the reduction in adipogenic abilities of APCs due to Impdh2 deficiency. In summary, we discovered that adipogenesis-mediated WAT expansion, induced by overnutrition, also contributes to metabolic abnormalities. Moreover, the pivotal role of Impdh2 in regulating adipogenesis in APCs offers a novel therapeutic approach to combat obesity.

Eltrombopag can promote platelet implantation after allogeneic hematopoietic stem cell transplantation as safely and similarly to thrombopoietin.

Background: Eltrombopag has demonstrated efficacy in treating low platelet (PLT) levels, but it remains unclear whether eltrombopag can promote PLT engraftment after hematopoietic stem cell transplantation (HSCT). Methods: Forty-one HSCT patients received eltrombopag 50 mg/d from +1 day until PLT >50 × 109/L or 1 month after HSCT. Fifty-one patients in the same period received thrombopoietin (TPO) to promote PLT graft after HSCT and served as a control group. Results: A total of 51 patients who applied TPO during the same period were treated as a control. In the eltrombopag group, the median time to white blood cells (WBC) graft was 12 days (range, 10-17 days) and the PLT graft was 15 days (range, 10-30 days), whereas for the patients in the TPO group, the median time to WBC and PLT graft was 12 days (range, 9-23 days) and 15.5 days (range, 9-41 days), respectively. In the first month after HSCT, the median WBC count in the eltrombopag group was 4.41 × 109/L (range, 0.87-40.01 × 109/L) and the median PLT was 89x109/L (range, 30-401 × 109/L); the median WBC and PLT \counts in the TPO group were 4.65 × 109/L (range, 0.99-23.63 × 109/L) and 86 × 109/L (range, 5-512 × 109/L), respectively. Patients in the TPO or eltrombopag group did not experience serious side effects after drug administration, and the difference in side effects on liver and kidney function between the two groups was not statistically significant. Conclusion: Eltrombopag is safe and similarly promotes platelet engraftment to thrombopoietin after allogeneic HSCT.

Antifungal activity of ruthenium (II) complex combined with fluconazole against drug-resistant Candida albicans in vitro and its anti-invasive infection in vivo.

With the abuse of antibiotics and azoles, drug-resistant Candida albicans infections have increased sharply and are spreading rapidly, thereby significantly reducing the antifungal efficacy of existing therapeutics. Several patients die of fungal infections every year. Therefore, there is an urgent requirement to develop new drugs. Accordingly, we synthesized a series of polypyridyl ruthenium (II) complexes having the formula [Ru (NN)2 (bpm)] (PF6)2 (N-N = 2,2'-bipyridine) (bpy, in Ru1), 1,10-phenanthroline (phen, in Ru2), 4,7-diphenyl-1,10-phenanthroline (DIP, in Ru3) (bpm = 2,2'-bipyrimidine) and studied their antifungal activities. Ru3 alone had no effect on the drug-resistant strains, but Ru3 combined with fluconazole (FLC) exhibited significant antifungal activity on drug-resistant strains. A high-dose combination of Ru3 and FLC exhibited direct fungicidal activity by promoting the accumulation of reactive oxygen species and damaging the cellular structure of C. albicans. Additionally, the combination of Ru3 and FLC demonstrated potent antifungal efficacy in vivo in a mouse model of invasive candidiasis. Moreover, the combination significantly improved the survival state of mice, restored their immune systems, and reduced renal injury. These findings could provide ideas for the development of ruthenium (II) complexes as novel antifungal agents for drug-resistant microbial stains.

HELLS Knockdown Inhibits the Malignant Progression of Lung Adenocarcinoma Via Blocking Akt/CREB Pathway by Downregulating KIF11.

Lung adenocarcinoma (LUAD) is a malignant tumor with the characteristics of progressive advancement and high mortality rate worldwide. We aimed to explore the role and mechanism of helicase Lymphoid-Specific (HELLS) in LUAD. Bioinformatics databases were applied to predict HELLS and kinesin family member (KIF)11 expression in LUAD tissues. The expressions of HELLS and KIF11 before and after HELLS knockdown were detected by RT-qPCR and western blot. After HELLS was knocked down, the proliferative, migratory, and invasive capabilities of A549 cells were evaluated. Cell apoptotic level was assessed using TUNEL. Western blot was employed to evaluate the expressions of Akt/CREB pathway-related proteins. The interaction between HELLS and KIF11 was analyzed using bioinformatics databases, and testified by Co-IP assay. Results revealed that HELLS and KIF11 expressions were significantly upregulated in LUAD cells and tissues. High HELLS and KIF11 expression was correlated with the poor prognosis of patients with LUAD. Additionally, HELLS knockdown suppressed the capabilities of LUAD cells to proliferate, migrate, and invade whereas promoted the cell apoptotic level. Moreover, HELLS could interact with KIF11 and had positive correlation with KIF11. Furthermore, KIF11 overexpression partially counteracted the impacts of HELLS knockdown on cell proliferative, migratory, invasive capabilities, and apoptotic level in LUAD cells. Besides, Akt/CREB pathway was blocked by HELLS silencing, which was restored by KIF11 overexpression. Collectively, HELLS knockdown blocked Akt/CREB pathway by downregulating KIF11 expression, thereby inhibiting LUAD cell proliferation, invasion, migration, and promoting apoptosis.

Core competence of midwives in township hospitals and its influencing factors-A cross-sectional study.

Objective: This study aimed to assess the core competence of midwives in township hospitals through a self-assessment questionnaire. The relationship between professional identity and core competence and the factors influencing midwives' core competence was also investigated. Method: Convenience sampling was conducted in 77 township hospitals in Ganzhou, Jiangxi Province, China, with 150 participants. The questionnaires were distributed online in November 2021. We conducted a descriptive data analysis, a correlation analysis of the two variables of professional identity and core competencies, and multivariate linear regression to analyse the influencing factors, including the sociodemographic information, the Midwife Core Competence Scale, and the Nurses' Professional Identity Scale scores. Results: The mean score for the core competence was 206.43 (±37.45) out of 270. The highest score was for pregnancy care (3.97 ± 0.70) and the lowest was for newborn care (3.72 ± 0.78). The independent sample t-test results and one-way analysis of variance showed that qualifications, midwifery training situation, and midwifery working years had differential effects on midwives' core competencies (P < 0.05). Multiple linear regression showed that qualifications, midwifery working years, and level of professional identity were influencing factors (P < 0.05). Conclusions: The core competencies of midwives in township hospitals were lower than those reported in other studies. Advancements in education, midwifery working years, and professional identity may increase midwives' core competencies.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): contemporary advances and current controversies.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory syndrome with characteristic clinical, radiological, and pathological features, and can be effectively treated with corticosteroid-based immunotherapies. The exact pathogenesis of CLIPPERS remains unclear, and specific diagnostic biomarkers are not available. According to the 2017 diagnostic criteria, probable CLIPPERS should be considered in middle-aged patients with subacute onset of pontocerebellar symptoms and typical punctuate and curvilinear gadolinium enhancement lesions ("salt-and-pepper" appearance) located in the hindbrain (especially pons) on magnetic resonance imaging. In addition, CLIPPERS-mimics, such as central nervous system (CNS) lymphoma, and several antibody-associated autoimmune CNS diseases (e.g., myelin oligodendrocyte glycoprotein antibody-associated disease, autoimmune glial fibrillary acidic protein astrocytopathy, and anti-N-methyl-D-aspartate receptor encephalitis), should be extensively excluded. The prerequisite for definite CLIPPERS is the perivascular T-cell-predominant inflammatory infiltration observed on pathological analysis. A biopsy is strongly suggested when clinical/radiological red flags are present. Most patients with CLIPPERS respond well to corticosteroids and have a good prognosis. Long-term low-dose corticosteroid maintenance therapy or corticosteroids coupled with immunosuppressants are recommended to prevent the recurrence of the syndrome. The potential progression of CLIPPERS to lymphoma has been suggested in some cases; therefore, at least 2-year clinical and radiological follow-up is essential. Here, we critically review the recent developments and provided an update on the clinical characteristics, diagnostic criteria, differential diagnoses, and therapeutic management of CLIPPERS. We also discuss the current controversies in this context that can be resolved in future research studies.

Serum indicators in functional high-risk multiple myeloma patients undertaking proteasome inhibitors therapy: a retrospective study.

OBJECTIVES: Multiple myeloma (MM) is a class of malignant plasma cell diseases. An increasing application of autologous stem cell transplantation (ASCT) and anti-myeloma agents represented by proteasome inhibitors (PIs) has improved the response rates and survival of MM patients. Patients progressing within 12 months were recently categorized with functional high-risk (FHR), which could not be clarified by existing genetic risk factors, with poor outcomes. Our study aimed to investigate clinical indices related to FHR and seek prognostic roles in transplant-eligible MM patients. METHODS: Demographic and individual baseline clinical characteristics were compared by using the Pearson's chi-square and Mann-Whitney U test. Progression-free survival (PFS) and overall survival (OS) were described by Kaplan-Meier estimates and compared using the log-rank test. Logistic regression analysis was used to assess the association of baseline characteristics at MM diagnosis with FHR status. RESULTS: From 18th January 2010 to 1st December 2022, 216 patients were included and divided into two groups according to the FHR status. There was no difference in baseline data between the two groups. Renal impairment (RI, Scr > 2 mg/dL) was common in MM patients and made sense in FHR status. AST levels were validated as independent predictors for FHR status (p = 0.019). DISCUSSION: Patients with RI or higher AST levels (AST > 40 U/L) tended to have worse outcomes. However, transplants had apparently improved prognoses. CONCLUSION: Therefore, in the PIs era, transplantations are still effective therapies for transplant-eligible MM patients.

Three new diterpenoids isolated from Euphorbia nematocypha Hand.-Mazz and their anti-fungal activity.

Three new diterpenoids, named nematocynine A-C (1-3), together with twelve known compounds (4-15) were isolated from the aerial part of Euphorbia nematocypha Hand.-Mazz (Hereinafter referred to E. nematocypha). Their structures were elucidated by detailed spectroscopic analysis and comparison with literature data. In addition, all the compounds were tested for their anti-candida albicans activities used alone or in combination with fluconazole against sensitive strain and resistant strain in vitro. Wherein only compound 11 shows weak activity against candida albicans resistant strain (MIC50 = 128.15 µg/mL) when used alone. Compounds 1, 4, 7, 8, 9, 10, 12, 13 and 15 in combination with fluconazole showed potent anti-fungal activities (MIC50 = 15 ± 5 µg/mL, FICI = 0.05 ± 0.04) against the Candida albicans resistant strain SC5314-FR. The synergistic effects were weaker against the Candida albicans resistant strain SC5314-FR when the compounds 2, 3, 5 and 14 were combined with fluconazole (FICI = 0.16 ± 0.06).

Myelin oligodendrocyte glycoprotein antibody and N-methyl-d-aspartate receptor antibody overlapping syndrome: insights from the recent case reports.

The overlapping of two or more types of neural autoantibodies in one patient has increasingly been documented in recent years. The coexistence of myelin oligodendrocyte glycoprotein (MOG) and N-methyl-d-aspartate receptor (NMDAR) antibodies is most common, which leads to a unique condition known as the MOG antibody and NMDAR antibody overlapping syndrome (MNOS). Here, we have reviewed the pathogenesis, clinical manifestations, paraclinical features, and treatment of MNOS. Forty-nine patients with MNOS were included in this study. They were young males with a median onset age of 23 years. No tumors were observed in the patients, and 24 of them reported prodromal symptoms. The most common clinical presentations were psychiatric symptoms (35/49) and seizures (25/49). Abnormalities on magnetic resonance imaging involved the brainstem (11/49), cerebellum (9/49), and parietal lobe (9/49). Most patients mostly responded to immunotherapy and had a good long-term prognosis. However, the overall recurrence rate of MNOS was higher than that of mono antibody-positive diseases. The existence of concurrent NMDAR antibodies should be suspected in patients with MOG antibody-associated disease having psychiatric symptoms, seizures, movement disorders, or autonomic dysfunction. Similarly, serum MOG antibody testing should be performed when patients with anti-NMDAR encephalitis present with atypical clinical manifestations, such as visual impairment and limb weakness, and neuroradiological findings, such as optic nerve, spinal cord, or infratentorial involvement or meningeal enhancement. Early detection of the syndrome and prompt treatment can be beneficial for these patients, and maintenance immunosuppressive therapy is recommended due to the high overall recurrence rate of the syndrome.

Retrospective Analysis of Pregnancy Outcomes Following External Cephalic Version for Breech Presentation.

Objective: We explored the feasibility and safety of external cephalic version (ECV) for cases of breech presentation. Methods: We retrospectively analyzed data from 158 singleton pregnant women with breech presentation at 36 weeks gestation, admitted to Guangzhou Hospital of Integrated Traditional and Western Medicine from January 2018 to March 2022. 42 underwent ECV, categorized as the ECV group, while 116 without ECV comprised the control group. Systematic collection and evaluation of pregnancy outcomes were conducted for both groups. Results: Within the control group, 16 cases experienced a spontaneous transition to head presentation, among which 14 cases resulted in successful vaginal deliveries. In 2 cases, cesarean deliveries were performed due to fetal macrosomia and persistent posterior occipital presentation. Furthermore, 2 cases of breech presentation in pregnant women were successfully delivered vaginally through breech traction, necessitating an emergency procedure due to the wide opening of the uterus. Within the ECV group, 28 cases were successfully inverted to the cephalic presentation. Among them, 1 case underwent an emergency cesarean delivery due to fetal distress during cephalic delivery, 3 cases required cesarean deliveries due to abnormal labor, and 24 cases were successfully delivered vaginally. The comparative analyses showed that the cesarean section rate (18/42 vs 100/116) and non-cephalic delivery rate (14/42 vs 100/116) in the ECV group were significantly lower than those in the control group (P < 0.001). There was no statistically significant differences between the two groups with respect to the rate of newborns with Apgar score < 7 (1/42 vs 3/116), premature rupture of membrane (3/42 vs 20/116), acute fetal distress (2/42 vs 2/116), and cord prolapse (0/42 vs 1/116) (P > 0.05). Conclusion: ECV can effectively reduce the rate of cesarean delivery and non-cephalic deliveries. However, it but requires strict adherence to indications and continuous monitoring.

Incidence and mortality of second primary malignancies after lymphoma: a population-based analysis.

BACKGROUND: Second primary malignancies (SPMs) account for an increasing proportion of human malignancies. We estimated the incidence, risk factors and outcomes in lymphoma survivors with SPMs. METHODS: Patients diagnosed with SPMs after primary lymphoma from 2010 to 2021 were included in this study. The incidence, mortality and clinical characteristics of SPMs in our center and Surveillance, Epidemiology, and End Results database were delineated and analyzed. Standardized incidence ratio quantified second cancer risk. RESULTS: A total of 2912 patients of lymphoma were included, 63 cases of SPM met the inclusion criteria, with the prevalence of SPMs after lymphoma was 2.16%. The male-to-female ratio of 2.32:1. The majority of these patients were older (≥60 years old, 61.90%) and previously treated with chemotherapy (68.25%). The common types among SPMs were digestive system tumors (42.86%), respiratory system tumors (20.63%) and urinary system tumors (12.70%). Additionally, cancer risks were significantly elevated after specific lymphoma though calculating the expected incidence. In terms of mortality, the diagnosis of SPMs was significantly associated with an increased risk of death over time. Moreover, although the outcome was favorable in some SPM subtypes (thyroid and breast cancer), other SPMs such as stomach and lung tumors had a dismal prognosis. CONCLUSION: With the improvement of medical standards, the survival of lymphoma patients has been prolonged. However, the incidence of SPM is increasing, particularly among men and older lymphoma survivors. Therefore, more attention should be invested in the SPM to further improve the prognosis of these patients.

Patterns of SPM incidence varied between China and Northern America.The incidence of SPM was higher among men and older lymphoma survivors.Patients with SPM are divided into low-risk and high-risk according to survival analysis.

Anti-adenylate kinase 5 encephalitis: Clinical characteristics, diagnosis, and management of this rare entity.

The spectrum and understanding of antibody-positive autoimmune encephalitis (AE) have expanded over the past few decades. In 2007, a rare subtype of AE known as anti-adenylate kinase 5 (AK5) encephalitis, was first reported. This disease is more common in elderly males, with limbic encephalitis as the core phenotype (characterized by subacute anterograde amnesia, sometimes with psychiatric symptoms, and rarely with seizures). Brain magnetic resonance imaging typically demonstrated initial temporal lobe T2/fluid-attenuated inversion recovery hyperintensities, and subsequent atrophy. No concomitant tumors have been found yet. AK5 antibody, targeting the intracellular antigen, is a biomarker for a non-paraneoplastic T-cell autoimmunity response, and can be detected in serum and cerebrospinal fluid using tissue-based and cell-based assays. Cytotoxic T-cell-mediating neuronal injury and loss play a pivotal role in the immunopathogenesis of anti-AK5 encephalitis. Patients mostly show poor response to immunotherapy and thus a poor prognosis in the long run. Herein, we review the literature and provide updated knowledge of this less-known entity, focusing on clinical characteristics, paraclinical findings, diagnosis process, and therapeutic approaches.

A Stable and Energy-Dense Polysulfide/Permanganate Flow Battery.

Redox flow batteries (RFBs) as promising technologies for energy storage have attracted burgeoning efforts and have achieved many advances in the past decades. However, for practical applications, the exploration of high-performance RFB systems is still of significance. In this work, inspired by the high solubility and low cost of both polysulfides and permanganates, the S/Mn RFBs with S42-/S22- and MnO4-/MnO42- as negative and positive redox pairs are demonstrated. Moreover, to solve the poor cycling performance caused by the sluggish kinetics of polysulfide-involved redox reactions and instability of the carbon felt (CF) electrode in the strong oxidative and corrosive catholyte, both the anode and cathode are designed to obtain high performance. Herein, the NiSx/Ni foam exhibiting electrocatalysis activity toward polysulfide ions is prepared and works as the anode while the graphene-modified carbon felt (G/CF) with high stability is fabricated and utilized as the cathode. Additionally, NaMnO4 with a high solubility limit (3.92 M) in the alkaline supporting electrolyte is preferred to KMnO4 as the redox-active molecule in the catholyte. The resulting S/Mn RFB cells show outstanding cell performance, such as high energy density (67.8 Wh L-1), long cycling lifetime with a temporal capacity fade of 0.025% h-1, and low chemical cost of electrolytes (17.31 $ kWh-1). Moreover, a three-cell stack shows good cycling stability over 100 cycles (226.8 h) with high performance, verifying the good scalability of the proposed S/Mn RFB system. Therefore, the present strategy provides a reliable candidate for stable, energy-dense, and cost-effective devices for future energy storage applications.

Redox Targeting-based Neutral Aqueous Flow Battery with High Energy Density and Low Cost.

Neutral aqueous flow batteries with common traits of the redox flow batteries, such as the independence of energy and power, scalability and operational flexibility, and additional merits of outstanding safety and low corrosivity show great promise for storing massive electrical energy from solar and wind energy. Particularly, the ferricyanide/ferrocyanide ([Fe(CN)6 ]3-/4- ) couple has been intensively employed as redox mediator to store energy in the catholyte ascribed to its abundance, low corrosivity, remarkable redox reversibility and stability. However, the low energy density arising from poor solubility of [Fe(CN)6 ]3-/4- restricts their commercial applications for energy storage systems. In this study, the practical energy density of a [Fe(CN)6 ]3-/4- -based catholyte is significantly boosted from 10.5 to 92.8 Wh L-1 by combining the counter-ion effect and the single-molecule redox-targeting (SMRT) reactions between [Fe(CN)6 ]3-/4- and Prussian blue (Fe4 [Fe(CN)6 ]3 , PB)/Prussian white (PW). Paired with concentrated K2 S anolyte, we demonstrate a neutral aqueous SMRT-based PB-Fe/S flow battery with ultra-long lifespan over 7000 cycles (4500 h) and ultra-low chemical cost of electrolytes in the cell as 19.26 $ kWh-1 . Remarkably, under the influences of SMRT reactions in the presence of PB granules in the catholyte, the capacity after 7000 cycles of the PB-Fe/S flow battery is 181.8 % of the initial capacity without PB.

The epidemiological patterns of non-Hodgkin lymphoma: global estimates of disease burden, risk factors, and temporal trends.

Background: The incidence of non-Hodgkin's lymphoma (NHL) has increased steadily over the past few decades. Elucidating its global burden will facilitate more effective disease management and improve patient outcomes. We explored the disease burden, risk factors, and trends in incidence and mortality in NHL globally. Methods: The up-to-date data on age-standardized incidence and mortality rates of NHL were retrieved from the GLOBOCAN 2020, CI5 volumes I-XI, WHO mortality database, and Global Burden of Disease (GBD) 2019, focusing on geographic disparities worldwide. We reported incidence and mortality by sex and age, along with corresponding age-standardized rates (ASRs), the average annual percentage change (AAPC), and future burden estimates to 2040. Results: In 2020, there were an estimated 545,000 new cases and 260,000 deaths of NHL globally. In addition, NHL resulted in 8,650,352 age-standardized DALYs in 2019 worldwide. The age-specific incidence rates varied drastically across world areas, at least 10-fold in both sexes, with the most pronounced increase trend found in Australia and New Zealand. By contrast, North African countries faced a more significant mortality burden (ASR, 3.7 per 100,000) than highly developed countries. In the past decades, the pace of increase in incidence and mortality accelerated, with the highest AAPC of 4.9 (95%CI: 3.6-6.2) and 6.8 (95%CI: 4.3-9.2) in the elderly population, respectively. Considering risk factors, obesity was positively correlated with age-standardized incidence rates (P< 0.001). And North America was the high-risk region for DALYs due to the high body mass index in 2019. Regarding demographic change, NHL incident cases are projected to rise to approximately 778,000 by 2040. Conclusion: In this pooled analysis, we provided evidence for the growing incidence trends in NHL, particularly among women, older adults, obese populations, and HIV-infected people. And the marked increase in the older population is still a public health issue that requires more attention. Future efforts should be directed at cultivating health awareness and formulating effective and locally tailored cancer prevention strategies, especially in most developing countries.

The smallest superatom Au4(PPh3)4I2 with two free electrons: synthesis, structure analysis, and electrocatalytic conversion of CO2 to CO.

Atomically precise metal nanoclusters (NCs) have emerged as a new class of ultrasmall nanoparticles with both free valence electrons and precise structures (from the metal core to the organic ligand shell) and provide great opportunities to understand the relationship between their structures and properties, such as electrocatalytic CO2 reduction reaction (eCO2RR) performance, at the atomic level. Herein, we report the synthesis and the overall structure of the phosphine and iodine co-protected Au4(PPh3)4I2 (Au4) NC, which is the smallest multinuclear Au superatom with two free e- reported so far. Single-crystal X-ray diffraction reveals a tetrahedral Au4 core stabilized by four phosphines and two iodides. Interestingly, the Au4 NC exhibits much higher catalytic selectivity for CO (FECO: > 60%) at more positive potentials (from -0.6 to -0.7 V vs. RHE) than Au11(PPh3)7I3 (FECO: < 60%), a larger 8 e- superatom, and Au(i)PPh3Cl complex; whereas the hydrogen evolution reaction (HER) dominates the electrocatalysis when the potential becomes more negative (FEH2 of Au4 = 85.8% at -1.2 V vs. RHE). Structural and electronic analyses reveal that the Au4 tetrahedron becomes unstable at more negative reduction potentials, resulting in decomposition and aggregation, and consequently the decay in catalytic performance of Au based catalysts towards the eCO2RR.

Derivation and validation of a nutrition-covered prognostic scoring system for extranodal NK/T-cell lymphoma.

Introduction: Patients with aggressive lymphomas are at high risk of losing body resources, resulting in malnutrition, immunodeficiency and inferior outcomes. Nutritional status is closely associated with survival, but often neglected in the prognostic assessment. This study aimed to explore the significance of nutritional status in extranodal NK/T-cell lymphoma (ENKTL). Methods: Univariate and multivariate Cox regression analyses were conducted to examine the significance of nutritional index on overall survival (OS) and progression-free survival (PFS). A nutrition-incorporated score system was constructed based on the multivariate results, and its calibration, discrimination and clinical utility were tested in the training and validation cohort. Results: Multivariate analysis revealed controlling nutritional status (CONUT) score could independently predict OS (HR 10.247, P=0.001) and PFS (HR 5.587, P=0.001) in addition to prognostic index of natural killer lymphoma plus EBV (PINK-E). Herein, a reformative model, CONUT-PINK-E, was developed and further verified in external validation cohort. CONUT-PINK-E classified patients into three risk grades with significant survival differences (P < 0.001). Compared with the current models, CONUT-PINK-E presented superior discrimination, calibration and clinical benefit. Discussion: In this study, we firstly verified that CONUT score was efficient to screen prognosis-related malnutrition in ENKTL. Moreover, we developed the first nutritional assessment-covered scoring system, CONUT-PINK-E, which might be a promising tool to provide references for clinical decision-making of ENKTL patients.