An Octacarboxylate-Linked Sodium Metal-Organic Framework with High Porosity.

Alkali metal-based metal-organic frameworks (MOFs) with permanent porosity are scarce because of their high tendency to coordinate with solvents such as water. However, these MOFs are lightweight and bear gravimetric benefits for gas adsorption related applications. In this study, we present the successful construction of a microporous MOF, designated as HIAM-111, built solely on sodium ions by using an octacarboxylate linker. The structure of HIAM-111 is based on 8-connected Na4 clusters and exhibits a novel topology with an underlying 32,42,8-c net. Remarkably, HAM-111 possesses a robust and highly porous framework with a BET surface area of 1561 m2/g, significantly surpassing that of the previously reported Na-MOFs. Further investigations demonstrate that HIAM-111 is capable of separating C2H2/CO2 and purifying C2H4 directly from C2H4/C2H2/C2H6 with high adsorption capacities. The current work may shed light on the rational design of robust and porous MOFs based on alkali metals.

Auranofin inhibits the occurrence of colorectal cancer by promoting mTOR-dependent autophagy and inhibiting epithelial-mesenchymal transformation.

Colorectal cancer (CRC) is one of the world's most common and deadly cancers. According to GLOBOCAN2020's global incidence rate and mortality estimates, CRC is the third main cause of cancer and the second leading cause of cancer-related deaths worldwide. The US Food and Drug Administration has approved auranofin for the treatment of rheumatoid arthritis. It is a gold-containing chemical that inhibits thioredoxin reductase. Auranofin has a number of biological activities, including anticancer activity, although it has not been researched extensively in CRC, and the mechanism of action on CRC cells is still unknown. The goal of this research was to see how Auranofin affected CRC cells in vivo and in vitro . The two chemical libraries were tested for drugs that make CRC cells more responsive. The CCK-8 technique was used to determine the cell survival rate. The invasion, migration, and proliferation of cells were assessed using a transwell test and a colony cloning experiment. An electron microscope was used to observe autophagosome formation. Western blotting was also used to determine the degree of expression of related proteins in cells. Auranofin's tumor-suppressing properties were further tested in a xenograft tumor model of human SW620 CRC cells. Auranofin dramatically reduced the occurrence of CRC by decreasing the proliferation, migration, and invasion of CRC cells, according to our findings. Through a mTOR-dependent mechanism, auranofin inhibits the epithelial-mesenchymal transition (EMT) and induces autophagy in CRC cells. Finally, in-vivo tests revealed that auranofin suppressed tumor growth in xenograft mice while causing no harm. In summary, auranofin suppresses CRC cell growth, invasion, and migration. Auranofin inhibits the occurrence and progression of CRC by decreasing EMT and inducing autophagy in CRC cells via a mTOR-dependent mechanism. These findings suggest that auranofin could be a potential chemotherapeutic medication for the treatment of human CRC.

Geriatric Nutritional Risk Index Combined with Calf Circumference Can be a Good Predictor of Prognosis in Patients Undergoing Surgery for Gastric or Colorectal Cancer.

OBJECTIVES: To explore the effect of combined hematological and physical measurement indicators on the prognosis of patients undergoing surgery for gastric or colorectal cancer and to screen for the best prognostic indicators. INTRODUCTION: Gastric and colorectal cancer is a widespread health concern worldwide and one of the major contributors to cancer-related death. The hematological and physical measurement indicators have been shown to associate with the prognosis of patients undergoing surgery for gastric or colorectal cancer, respectively, but it is still unclear whether the combination of the two can reflect the prognosis more effectively. METHODS: Thirteen hematological indicators and 5 physical measurement indicators were selected in this study, and the most promising ones were screened using LASSO regression. Then, the best prognostic indicators were selected by time-ROC curves. Survival curves were constructed using the Kaplan-Meier method, and the effects of hematological and physical measurement indicators on the prognosis of patients undergoing surgery for gastric or colorectal cancers were evaluated by Cox proportional risk regression analysis. In addition, the relationship between hematological and physical measurement indicators on secondary outcomes, including length of stay, hospitalization costs, intensive care unit (ICU) admission, and patients' subjective global assessment scores (PGSGA), was explored. RESULTS: After initial screening, among the hematological indicators, the geriatric nutritional risk index (GNRI) showed the highest mean area under the curve (AUC) values. Among body measures, calf circumference (CC) showed the highest mean AUC value. Further analyses showed that the combination of combined nutritional prognostic index (GNRI) and calf circumference (CC) (GNRI-CC) had the best performance in predicting the prognosis of patients undergoing surgery for gastric or colorectal cancers. Low GNRI, low CC, and low GNRI-low CC increased the risk of death by 44%, 48%, and 104%, respectively. Sensitivity analyses showed the same trend. In addition, low GNRI-low CC increased the risk of malnutrition by 17%. CONCLUSION: This study emphasizes that a combination of blood measures and body measures is essential to accurately assess the prognosis of patients undergoing surgery for gastric or colorectal cancers. The GNRI-CC is a good prognostic indicator and can also assess the risk of possible malnutrition.

Photoinduced Decarboxylative Difluoroalkylation and Perfluoroalkylation of α-Fluoroacrylic Acids.

Herein, a novel and practical methodology for the photoinduced decarboxylative difluoroalkylation and perfluoroalkylation of α-fluoroacrylic acids is reported. A wide range of α-fluoroacrylic acids can be used as applicable feedstocks, allowing for rapid access to structurally important difluoroalkylated and polyfluoroalkylated monofluoroalkenes with high Z-stereoselectivity under mild conditions. The protocol demonstrates excellent functional group compatibility and provides a platform for modifying complex biologically active molecules.

Causal relationships between vitamin E and multiple kidney diseases: evidence from trans-ethnic Mendelian randomization study.

PURPOSE: The association between vitamin E and the risk of kidney disease is well documented in observational studies, but the role of vitamin E in kidney disease remain inconclusive. Here, we evaluated the causal effect of vitamin E on the risk of multiple kidney diseases, including chronic kidney disease, membranous nephropathy, diabetic nephropathy, IgA nephropathy, and dialysis. METHODS: We conducted a two-sample Mendelian randomization analysis from large-scale trans-ancestry genome-wide association studies to determine whether there was a significant causal relationship between vitamin E and multiple kidney diseases in European, American, and Asian ancestry. Instrumental genetic variants associated with vitamin E were selected, and summary statistic-based methods of inverse variance weighted, MR Egger, weighted median, simple mode, and weighted mode methods were conducted. Pleiotropy and sensitivity were assessed. RESULTS: We obtained 87 instrumental genetic variants in European ancestry and found no causal relationship between vitamin E and chronic kidney disease, membranous nephropathy, diabetic nephropathy, IgA nephropathy, and dialysis with no heterogeneity and pleiotropy. We obtained 18 instrumental genetic variants in Asian ancestry and vitamin E had no causal relationship with membranous nephropathy, diabetic nephropathy, and IgA nephropathy with no heterogeneity and pleiotropy. In African ancestry, 25 instrumental genetic variants were obtained and no causal relationship was identified with no heterogeneity and pleiotropy. CONCLUSION: Our study first suggested plausible non-causal associations between vitamin E and multiple kidney diseases among different ancestry.

Discovery of cinnamamide/ester triazole hybrids as potential treatment for Alzheimer's disease.

Developing multitargeted ligands as promising therapeutics for Alzheimer's disease (AD) has been considered important. Herein, a novel class of cinnamamide/ester-triazole hybrids with multifaceted effects on AD was developed based on the multitarget-directed ligands strategy. Thirty-seven cinnamamide/ester-triazole hybrids were synthesized, with most exhibiting significant inhibitory activity against Aß-induced toxicity at a single concentration in vitro. The most optimal hybrid compound 4j inhibited copper-induced Aß toxicity in AD cells. its action was superior to that of donepezil and memantine. It also moderately inhibited intracellular AChE activity and presented favorable bioavailability and blood-brain barrier penetration with low toxicity in vivo. Of note, it ameliorated cognitive impairment, neuronal degeneration, and Aß deposition in Aß1-42-injured mice. Mechanistically, the compound regulated APP processing by promoting the ADAM10-associated nonamyloidogenic signaling and inhibiting the BACE1-mediated amyloidogenic pathway. Moreover, it suppressed intracellular AChE activity and tau phosphorylation. Therefore, compound 4j may be a promising multitargeted active molecule against AD.

Glial growth factor 2 treatment alleviates ischemia and reperfusion-damaged integrity of the blood-brain barrier through decreasing Mfsd2a/caveolin-1-mediated transcellular and Pdlim5/YAP/TAZ-mediated paracellular permeability.

The impairment of blood-brain barrier (BBB) integrity is the pathological basis of hemorrhage transformation and vasogenic edema following thrombolysis and endovascular therapy. There is no approved drug in the clinic to reduce BBB damage after acute ischemic stroke (AIS). Glial growth factor 2 (GGF2), a recombinant version of neuregulin-1ß that can stimulates glial cell proliferation and differentiation, has been shown to alleviate free radical release from activated microglial cells. We previously found that activated microglia and proinflammatory factors could disrupt BBB after AIS. In this study we investigated the effects of GGF2 on AIS-induced BBB damage as well as the underlying mechanisms. Mouse middle cerebral artery occlusion model was established: mice received a 90-min ischemia and 22.5 h reperfusion (I/R), and were treated with GGF2 (2.5, 12.5, 50 ng/kg, i.v.) before the reperfusion. We showed that GGF2 treatment dose-dependently decreased I/R-induced BBB damage detected by Evans blue (EB) and immunoglobulin G (IgG) leakage, and tight junction protein occludin degradation. In addition, we found that GGF2 dose-dependently reversed AIS-induced upregulation of vesicular transcytosis increase, caveolin-1 (Cav-1) as well as downregulation of major facilitator superfamily domain containing 2a (Mfsd2a). Moreover, GGF2 decreased I/R-induced upregulation of PDZ and LIM domain protein 5 (Pdlim5), an adaptor protein that played an important role in BBB damage after AIS. In addition, GGF2 significantly alleviated I/R-induced reduction of YAP and TAZ, microglial cell activation and upregulation of inflammatory factors. Together, these results demonstrate that GGF2 treatment alleviates the I/R-compromised integrity of BBB by inhibiting Mfsd2a/Cav-1-mediated transcellular permeability and Pdlim5/YAP/TAZ-mediated paracellular permeability.

Exploring the impact of women-specific reproductive factors on phenotypic aging and the role of life's essential 8.

BACKGROUND: Aging is an inevitable biological process. Accelerated aging renders adults more susceptible to chronic diseases and increases their mortality rates. Previous studies have reported the relationship between lifestyle factors and phenotypic aging. However, the relationship between intrinsic factors, such as reproductive factors, and phenotypic aging remains unclear. METHODS: This study utilized data from the National Health and Nutrition Examination Survey (NHANES), spanning from 1999 to 2010 and 2015-2018, with 14,736 adult women. Random forest imputation was used to handle missing covariate values in the final cohort. Weighted linear regression was utilized to analyze the relationship between women-specific reproductive factors and PhenoAgeAccel. Considering the potential impact of menopausal status on the results, additional analyses were conducted on premenopausal and postmenopausal participants. Additionally, the Life's Essential 8 (LE8) was used to investigate the impact of healthy lifestyle and other factors on the relationship between women-specific reproductive factors and PhenoAgeAccel. Stratified analyses were conducted based on significant interaction p-values. RESULTS: In the fully adjusted models, delayed menarche and gynecological surgery were associated with increased PhenoAgeAccel, whereas pregnancy history were associated with a decrease. Additionally, early or late ages of menopause, first live birth, and last live birth can all negatively impact PhenoAgeAccel. The relationship between women-specific reproductive factors and PhenoAgeAccel differs between premenopausal and postmenopausal women. High LE8 scores positively impacted the relationship between certain reproductive factors (age at menarche, age at menopause, age at first live birth, and age at last live birth) and phenotypic age acceleration. Stratified analysis showed significant interactions for the following variables: BMI with age at menarche, pregnancy history, and age at menopause; ethnicity with age at menopause, age at first live birth, and parity; smoking status with use of contraceptive pills and gynecologic surgery; hypertension with use of contraceptive pills, pregnancy history, and age at menopause. CONCLUSION: Delayed menarche, gynecological surgery, and early or late ages of menopause, first live birth, and last live birth are associated with accelerated phenotypic aging. High LE8 score may alleviate the adverse effects of reproductive factors on phenotypic aging.

[Chemical composition analysis of Ganoderma lucidum based on UPLC-Orbitrap-HRMS and virtual screening of FXR activators for treatment of liver fibrosis].

The chemical composition of Ganoderma lucidum ethanol extracts was systematically analyzed and identified by ultra-high performance liquid chromatography-quadrupole electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Orbitrap-HRMS). The fragmentation pattern of the representative chemical compounds was summarized, and the potential anti-liver fibrosis active compounds of G. lucidum acting on the farnesoid X receptor(FXR) target were studied to elucidate its pharmacodynamic substance basis. Preliminarily, 95 chemical constituents of G. lucidum ethanol extracts were identified, including 24 ganoderic acids, 9 ganoderenic acids, 13 lucidenic acids, 3 ganolucidic acids, 1 ganoderma lactone, 40 other triterpenoids, 4 fatty acids, and 1 other constituent. In addition, the fragmentation patterns of the representative compounds were also analyzed. The structural characteristics of ganoderic acids and ganoderenic acids were the C30 skeleton, containing free-COOH and-OH groups, which could easily lose H_2O and CO_2 to form fragment ions. The D-ring was mostly a five-membered ring, which was prone to breakage. Lucidenic acids were the lanosterolane-type of the C27 skeleton, and the side-chain structure became shorter and contained the same free-COOH and-OH compared with ganoderic acids, which had been reduced from 8 to 5 cartons and prone to lose H_2O and CO_2. Then, six reported FXR receptor agonists were selected to form a training set for establishing a pharmacophore model based on FXR ligands. The 95 identified chemical constituents of G. lucidum were matched with the pharmacophore, and the optimal pharmacophore model 02(sensitivity=0.750 00, specificity=0.555 56, ROC=0.750) was selected for the virtual screening of the G. lucidum compound library through the validation of the test set. Finally, 31 potential G. lucidum active constituents were screened and chosen to activate the FXRs. The ADMET results showed that ganoderic acid H and lucidenic acid J had less than 90% plasma protein binding rate and no hepatotoxicity, which could be used as FXR activators for developing clinical drugs for the treatment of liver fibrosis, either alone or in combination.

AQP4-A25Q Point Mutation in Mice Depolymerizes Orthogonal Arrays of Particles and Decreases Polarized Expression of AQP4 Protein in Astrocytic Endfeet at the Blood-Brain Barrier.

Aquaporin-4 (AQP4) is characterized by the formation of orthogonal arrays of particles (OAPs) comprising its M1 and M23 isoforms in the plasma membrane. However, the biological importance of OAP formation is obscure. Here, we developed an OAP depolymerization male mouse model by transgenic knock-in of an AQP4-A25Q mutation. Analyses of the mutant brain tissue using blue native polyacrylamide gel electrophoresis, super-resolution imaging, and immunogold electron microscopy revealed remarkably reduced OAP structures and glial endfeet localization of the AQP4-A25Q mutant protein without effects on its overall mRNA and protein expression. AQP4A25Q/A25Q mice showed better survival and neurologic deficit scores when cerebral edema was induced by water intoxication or middle cerebral artery occlusion/reperfusion. The brain water content and swelling of pericapillary astrocytic endfeet processes in AQP4A25Q/A25Q mice were significantly reduced, functionally supporting decreased AQP4 protein expression at the blood-brain barrier. The infarct volume and neuronal damage were also reduced in AQP4A25Q/A25Q mice in the middle cerebral artery occlusion/reperfusion model. Astrocyte activation in the brain was alleviated in AQP4A25Q/A25Q mice, which may be associated with decreased cell swelling. We conclude that the OAP structure of AQP4 plays a key role in its polarized expression in astrocytic endfeet processes at the blood-brain barrier. Therefore, our study provided new insights into intervention of cerebral cellular edema caused by stroke and traumatic brain injury through regulating AQP4 OAP formation.SIGNIFICANCE STATEMENT Aquaporin-4 (AQP4) is characterized by orthogonal arrays of particles (OAPs) comprising the M1 and M23 isoforms in the membrane. Here, an OAP depolymerization male mouse model induced by AQP4-A25Q mutation was first established, and the functions of OAP depolymerization in cerebral edema have been studied. The results revealed that AQP4 lost its OAP structure without affecting AQP4 mRNA and protein levels in AQP4-A25Q mice. AQP4-A25Q mutation mice has neuroprotective effects on cerebral edema induced by water intoxication and middle cerebral artery occlusion/reperfusion through relieving the activation of astrocytes and suppressed microglia-mediated neuroinflammation. We concluded that the OAP structure of AQP4 plays a key role in its polarized expression in astrocytic endfeet processes at the blood-brain barrier. Therefore, our study provided new insights into intervention of cerebral cellular edema caused by stroke and traumatic brain injury through regulating AQP4 OAP formation.

Muscle distribution in relation to all-cause and cause-specific mortality in young and middle-aged adults.

BACKGROUND: The relationship between muscle and prognosis, especially that between muscle distribution across different body parts, and the related prognosis is not well established. OBJECTIVE: To investigate the relationship between muscle distribution and all-cause and cause-specific mortality and their potential modifiers. DESIGN: Longitudinal cohort study. C-index, IDI, and NRI were used to determine the best indicator of prognosis. COX regression analysis was performed to explore the relationship between variables and outcomes. Interaction and subgroup analyses were applied to identify the potential modifiers. PARTICIPANTS: A total of 5052 participants (weighted: 124,841,420) extracted from the NHANES 2003-2006 of median age 45 years and constituting 50.3% men were assessed. For validation, we included 3040 patients from the INSCOC cohort in China. MAIN MEASURES: Muscle mass and distribution. KEY RESULTS: COX regression analysis revealed that upper limbs (HR = 0.41, 95% CI 0.33-0.51), lower limbs (HR = 0.54, 95% CI 0.47-0.64), trunk (HR = 0.71, 95% CI, 0.59-0.85), gynoid (HR = 0.47, 95% CI 0.38-0.58), and total lean mass (HR = 0.55, 95% CI 0.45-0.66) were all associated with the better survival of participants (P trend < 0.001). The changes in the lean mass ratio of the upper and lower limbs and the lean mass ratio of the android and gynoid attenuated the protective effect of lean mass. Age and sex acted as potential modifiers, and the relationship between lean mass and the prognosis was more significant in men and middle-aged participants when compared to that in other age groups. Sensitive analyses depicted that despite lean mass having a long-term impact on prognosis (15 years), it has a more substantial effect on near-term survival (5 years). CONCLUSION: Muscle mass and its distribution affect the prognosis with a more significant impact on the near-term than that on the long-term prognosis. Age and sex acted as vital modifiers.

Tuning and Directing Energy Transfer from the Blue to Near-Infrared Range in Multicomponent Metal-Organic Frameworks with seh Topology.

Luminescent metal-organic frameworks (MOFs) are emerging as one of several promising materials to study light-harvesting and energy-transfer processes. However, it is still a big challenge to tune and direct energy transfer in luminescent MOFs-based light-harvesting system. Herein, a series of new light-harvesting zinc-based luminescent MOFs with seh underlying topology were reported by successfully integrating 2,1,3-benzothiadiazole and its derivative-based carboxylic acids and pyridine-contained linkers into one structure. The strong spectra overlap between the emission and absorption spectra of carboxylic acids and pyridine-type linkers afforded an ideal platform to realize efficient energy transfer from the blue to near-infrared range. This work provides a novel approach to the rational design and synthesis of MOFs-based multicomponent light-harvesting materials with tunable energy transfer to mimic natural photosynthetic processes.

The value of CRP-albumin-lymphocyte index (CALLY index) as a prognostic biomarker in patients with non-small cell lung cancer.

OBJECTIVE: The C-reactive protein-albumin-lymphocyte (CALLY) index is a new index related to inflammation, immunity, and nutrition. We investigated whether it can predict the prognosis of patients with non-small cell lung cancer (NSCLC) and developed a prognostic model including CALLY index. RESEARCH METHODS AND PROCEDURES: Data from patients with NSCLC who were followed up in the INSCOC database from May 2013 to December 2018 were retrospectively analyzed. Simple random sampling by splitting these patients into training (n = 1307) and validation cohorts (n = 557) resulted in a sample size ratio of 7:3. Using the results of COX regression analysis of the training cohort, a nomogram model for predicting 3- and 5-year overall survival (OS) was established and validated internally. The calibration and clinical decision curve were used to evaluate the prediction accuracy and clinical application ability of the nomogram and compared with the TNM staging system for lung cancer. RESULTS: Sex, TNM stage, surgical treatment, BMI, CALLY, and HGS were independent risk factors for the prognosis of NSCLC patients. The OS of NSCLC patients with a low CALLY index score was significantly worse than that of patients with a high CALLY index (P < 0.001). The CALLY-based nomogram had a good predictive prognostic power, with a C-index of 0.697. Compared with the traditional TNM staging system, our prognostic nomogram had better resolution and accuracy in predicting the 3-year and 5-year OS. Decision curve analysis showed that this prognostic model has a clinical application value. CONCLUSIONS: The CALLY index is a valuable biomarker for evaluating the prognosis of patients with lung cancer. The nomogram based on the CALLY index is highly effective in predicting OS in patients with NSCLC. The results of this study provide a reference tool for clinicians to guide the personalized treatment of patients with lung cancer.

Association between the Dietary Inflammatory Index and All-Cause Mortality in Adults with Obesity.

INTRODUCTION: The dietary inflammatory index (DII) is associated with numerous chronic noncommunicable diseases. Previous studies have shown that the pro-inflammatory DII categories are associated with abdominal and simple obesity. However, the association between DII and mortality in patients with abdominal obesity and simple overweight or obesity remains unclear. METHODS: We used data from the US National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. A DII >0 (positive DII) was defined as a pro-inflammatory diet. A restricted cubic spline curve was used to describe the trend between DII and all-cause mortality. We then examined the association between DII and all-cause mortality in different body types using a Cox regression analysis and investigated the differences between sexes. Finally, the mediating effects of systemic inflammation were explored. RESULTS: A pro-inflammatory diet increased all-cause mortality in adults with abdominal obesity (aHR: 1.31, 95% confidence interval [CI]: 1.11-1.54; p < 0.001) and with simple overweight or obesity (aHR: 1.30, 95% CI: 1.11-1.53; p < 0.001). In addition, the most pro-inflammatory DII increased the risk of mortality by 43% (hazard ratio [HR]: Q4 vs. Q1 = 1.43, 95% CI = 1.14-1.79; p = 0.002; p for trend = 0.003) and 39% (HR: Q4 vs. Q1 = 1.39, 95% CI = 1.13-1.74; p = 0.003; p for trend = 0.009) in participants with abdominal obesity and with simple overweight or obesity, respectively. However, this association was not present in normal-sized participants. Compared with men, women resisted the effects of a pro-inflammatory diet. Mediation analysis showed that white blood cell and neutrophil were mediators of the association between DII and all-cause mortality (p < 0.001). CONCLUSION: A pro-inflammatory diet is associated with all-cause mortality in adults with abdominal obesity and simple overweight or obesity, and this effect differs between men and women. Systemic inflammation may mediate the association between DII and all-cause mortality.

Size- and Emission-Controlled Synthesis of Full-Color Luminescent Metal-Organic Frameworks for Tryptophan Detection.

The development of nanoscaled luminescent metal-organic frameworks (nano-LMOFs) with organic linker-based emission to explore their applications in sensing, bioimaging and photocatalysis is of great interest as material size and emission wavelength both have remarkable influence on their performances. However, there is lack of platforms that can systematically tune the emission and size of nano-LMOFs with customized linker design. Herein two series of fcu- and csq-type nano-LMOFs, with precise size control in a broad range and emission colors from blue to near-infrared, were prepared using 2,1,3-benzothiadiazole and its derivative based ditopic- and tetratopic carboxylic acids as the emission sources. The modification of tetratopic carboxylic acids using OH and NH2 as the substituent groups not only induces significant emission bathochromic shift of the resultant MOFs, but also endows interesting features for their potential applications. As one example, we show that the non-substituted and NH2 -substituted nano-LMOFs exhibit turn-off and turn-on responses for highly selective and sensitive detection of tryptophan over other nineteen natural amino acids. This work sheds light on the rational construction of nano-LMOFs with specific emission behaviours and sizes, which will undoubtedly facilitate their applications in related areas.

A Microporous Metal-Organic Framework Incorporating Both Primary and Secondary Building Units for Splitting Alkane Isomers.

We demonstrate the assembly of a mononuclear metal center, a hexanuclear cluster, and a V-shaped, trapezoidal tetracarboxylate linker into a microporous metal-organic framework featuring an unprecedented 3-nodal (4,4,8)-c lyu topology. The compound, HIAM-302, represents the first example that incorporates both a primary building unit and a hexanuclear secondary building unit in one structure, which should be attributed to the desymmetrized geometry of the organic linker. HIAM-302 possesses optimal pore dimensions and can separate monobranched and dibranched alkanes through selective molecular sieving, which is of significant value in the petrochemical industry.

Reticular Chemistry with Art: A Case Study of Olympic Rings-Inspired Metal-Organic Frameworks.

Herein, we demonstrate the successful utilization of reticular chemistry as an excellent designing strategy for the deliberate construction of a zirconium-tetracarboxylate metal-organic framework (MOF) inspired by the Olympic rings. HIAM-4017, with an unprecedented (4,8)-c underlying net topology termed jcs, was developed via insightful reconstruction of the rings and judicious design of a nonsymmetric organic linker. HIAM-4017 exhibits high porosity and excellent chemical and thermal stability. Furthermore, excited-state intramolecular proton transfer (ESIPT) was achieved in an isoreticular MOF, HIAM-4018, with a large Stokes shift of 155 nm as a result of introducing the hydroxyl group to the linker skeleton to induce OH···N interactions. Such interactions were analyzed thoroughly by employing the time-dependent density functional theory (TD-DFT). Because of their good thermal and chemical stability, and strong luminescence, nanosized HIAM-4017 and HIAM-4018 were fabricated and used for Cr2O72- detection. Both MOFs demonstrate excellent sensitivity and selectivity. This work represents a neat example of building structure- and property-specific MOFs guided by reticular chemistry.

Speech silence character as a diagnostic biomarker of early cognitive decline and its functional mechanism: a multicenter cross-sectional cohort study.

BACKGROUND: Language deficits frequently occur during the prodromal stages of Alzheimer's disease (AD). However, the characteristics of linguistic impairment and its underlying mechanism(s) remain to be explored for the early diagnosis of AD. METHODS: The percentage of silence duration (PSD) of 324 subjects was analyzed, including patients with AD, amnestic mild cognitive impairment (aMCI), and normal controls (NC) recruited from the China multi-center cohort, and the diagnostic efficiency was replicated from the Pitt center cohort. Furthermore, the specific language network involved in the fragmented speech was analyzed using task-based functional magnetic resonance. RESULTS: In the China cohort, PSD increased significantly in aMCI and AD patients. The area under the curve of the receiver operating characteristic curves is 0.74, 0.84, and 0.80 in the classification of NC/aMCI, NC/AD, and NC/aMCI+AD. In the Pitt center cohort, PSD was verified as a reliable diagnosis biomarker to differentiate mild AD patients from NC. Next, in response to fluency tasks, clusters in the bilateral inferior frontal gyrus, precentral gyrus, left inferior temporal gyrus, and inferior parietal lobule deactivated markedly in the aMCI/AD group (cluster-level P < 0.05, family-wise error (FWE) corrected). In the patient group (AD+aMCI), higher activation level of the right pars triangularis was associated with higher PSD in in both semantic and phonemic tasks. CONCLUSIONS: PSD is a reliable diagnostic biomarker for the early stage of AD and aMCI. At as early as aMCI phase, the brain response to fluency tasks was inhibited markedly, partly explaining why PSD was elevated simultaneously.

Maternal Exposure to Air Pollution Is Associated with Neonatal Jaundice: A Retrospective Cohort Study.

OBJECTIVE: To evaluate the association between maternal ambient pollutant exposure and neonatal jaundice in multiple pollutant species and examine sex differences. STUDY DESIGN: Epidemiologic study: Records of 13 297 newborns (6153 male, 7144 female) born in Taichung, Taiwan were obtained from a national database. Average concentrations of prenatal air pollutants 3 months prior to birth were divided into low, middle, and high levels. Neonatal jaundice phototherapy rates between mothers who suffered varying air pollutant levels were compared. Clinical study: Three hundred seventy-six newborns (189 male, 187 female) born and received jaundice treatment with phototherapy in a hospital in Taichung, Taiwan were recruited. The correlation between prenatal exposure to air pollutants 3 months prior to birth, newborn's serum bilirubin, and serum hemoglobin were calculated. RESULTS: Epidemiologic study: Male newborns born to mothers exposed to high carbon monoxide (CO), nitric oxide (NO), nitrogen dioxide (NO2), and methane (CH4) levels had higher phototherapy rates. In female newborns, the same was noted for CO and CH4. Clinical study: Male newborns had a positive correlation between CO, ≤2.5 µm diameter particles, ≤10 µm diameter particles, NO, NO2, nonmethane hydrocarbon, and CH4 exposure 3 months prior to birth and serum bilirubin levels. Female newborns had a positive correlation for CH4. A positive correlation between CO, ≤2.5 µm diameter particles, ≤10 µm diameter particles, NO2, nonmethane hydrocarbon, CH4 exposure, and serum hemoglobin levels was noted in male newborns. CONCLUSION: Maternal exposure to air pollutants may increase neonatal jaundice treatment rates for phototherapy and higher neonatal serum total bilirubin level. Higher hemoglobin levels because of higher pollutant exposures may explain our findings. The association was more obvious in male newborns.

Lymphocyte to C-reactive protein ratio could better predict the prognosis of patients with stage IV cancer.

BACKGROUND: Systemic inflammation is currently regarded as a hallmark of cancer. This study aimed to accurately clarify the prognostic value of various inflammatory markers in patients with stage IV cancer. METHODS: This study assessed 2,424 patients with cancer diagnosed with cancer in tumor, node, metastasis (TNM) stage IV. After evaluating the predictive value of 13 inflammatory indicators for patient prognosis using the C index, the lymphocyte C-reactive protein ratio (LCR) was selected to elucidate the prognostic and predictive values in patients with stage IV cancer. Kaplan-Meier and Cox proportional hazards regression models were used to analyze long-term survival. RESULTS: A total of 1,457 men (60.1%) and 967 women (39.9%) diagnosed with TNM stage IV cancer were enrolled. A ratio of 2,814 was defined as the optimal cut-off value for the LCR. The LCR was the most accurate prognosis predictor for patients with stage IV cancer among the 13 inflammatory nutritional markers evaluated. The multivariate-adjusted restricted cubic spline plot suggested that LCR had an L-shaped dose-response association with all-cause mortality risk. Patients with lower LCR levels tended to present with worse prognoses. Kaplan-Meier curves and log-rank test results showed that the high LCR groups (LCR ≥ 2,814) exhibited a better prognosis, whereas patients with stage IV cancer of different sex and tumor types (for example, gastrointestinal tumor, non-gastrointestinal tumor, and lung cancer) had a worse survival time. CONCLUSION: The LCR score can be regarded as a stable and useful biomarker to predict prognosis in patients with TNM stage IV compared to other evaluated inflammation indicators.