Successful Outcome of a Patient with Concomitant Pancreatic and Renal Carcinoma Receiving Secoisolariciresinol Diglucoside Therapy Alone: A Case Report.

Introduction: Pancreatic cancer (PC) is among the deadliest malignancies. Kidney cancer (KC) is a common malignancy globally. Chemo- or radio-therapies are not very effective to control PC or KC, and overdoses often cause severe site reactions to the patients. As a result, novel treatment strategies with high efficacy but without toxic side effects are urgently desired. Secoisolariciresinol diglucoside (SDG) belongs to plant lignans with potential anticancer activities, but clinical evidence is not available in PC or KC treatment. Patient Concerns: We report a rare case of an 83-year-old female patient with pancreatic and kidney occupying lesions that lacked the conditions to receive surgery or chemo- or radiotherapy. Diagnosis: Pancreatic and kidney cancers. Interventions: We gave dietary SDG to the patient as the only therapeutics. Outcomes: SDG effectively halted progression of both PC and KC. All clinical manifestations, including bad insomnia, loss of appetite, stomach symptoms, and skin itching over the whole body, all disappeared. The initial massive macroscopic hematuria became microscopic and infrequent, and other laboratory results also gradually returned to normal. Most of the cancer biomarkers, initially high such as CEA, CA199, CA724, CA125, came down rapidly, among which CA199 changed most radically. This patient has had progression-free survival of one year so far. Conclusion: These results demonstrate the potent inhibitory effects of SDG on PC and KC of this patient and provide promising novel therapeutics for refractory malignant tumors.

Linkages Make a Difference in the Photoluminescence of Covalent Organic Frameworks.

Covalent organic frameworks (COFs) with structural designability and tunability of photophysical properties enable them to be a promising class of organic luminescent materials by incorporating well-designed fluorescent units directly into the periodic skeletons. The photophysical properties of COFs are mainly affected by the structural features, which determine the conjugation degree, charge delocalization ability, and exciton dynamics of COFs. To understand the relationship between COF structures and their photophysical properties, two COFs with the same pyrene chromophore units but different linkages (imine or vinylene) were designed and synthesized. Interestingly, different linkages endow COFs with huge differences in solid-state photoluminescence quantum yield (PLQY) for imine- and vinylene-linked pyrene-based COFs, which possess PLQY values of 0.34 % and 15.43 %, respectively. The femtosecond-transient absorption spectra and time-dependent density functional theory reveal the different charge-transfer pathways in imine- and vinylene-linked COFs, which influence the exciton relaxation way and fluorescence intensity. In addition, an effective white-light device was obtained by coating the vinylene-linked COF on a light-emitting diode strip.

A Fully Conjugated Covalent Organic Framework with Oxidative and Reductive Sites for Photocatalytic Carbon Dioxide Reduction with Water.

Constructing a powerful photocatalytic system that can achieve the carbon dioxide (CO2 ) reduction half-reaction and the water (H2 O) oxidation half-reaction simultaneously is a very challenging but meaningful task. Herein, a porous material with a crystalline topological network, named viCOF-bpy-Re, was rationally synthesized by incorporating rhenium complexes as reductive sites and triazine ring structures as oxidative sites via robust -C=C- bond linkages. The charge-separation ability of viCOF-bpy-Re is promoted by low polarized π-bridges between rhenium complexes and triazine ring units, and the efficient charge-separation enables the photogenerated electron-hole pairs, followed by an intramolecular charge-transfer process, to form photogenerated electrons involved in CO2 reduction and photogenerated holes that participate in H2 O oxidation simultaneously. The viCOF-bpy-Re shows the highest catalytic photocatalytic carbon monoxide (CO) production rate (190.6 µmol g-1 h-1 with about 100 % selectivity) and oxygen (O2 ) evolution (90.2 µmol g-1 h-1 ) among all the porous catalysts in CO2 reduction with H2 O as sacrificial agents. Therefore, a powerful photocatalytic system was successfully achieved, and this catalytic system exhibited excellent stability in the catalysis process for 50 hours. The structure-function relationship was confirmed by femtosecond transient absorption spectroscopy and density functional theory calculations.

Transcription factor Dmrt1 triggers the SPRY1-NF-κB pathway to maintain testicular immune homeostasis and male fertility.

Bacterial or viral infections, such as Brucella, mumps virus, herpes simplex virus, and Zika virus, destroy immune homeostasis of the testes, leading to spermatogenesis disorder and infertility. Of note, recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells, leading to male reproductive dysfunction. Due to the many side effects associated with antibiotic therapy, finding alternative treatments for inflammatory injury remains critical. Here, we found that Dmrt1 plays an important role in regulating testicular immune homeostasis. Knockdown of Dmrt1 in male mice inhibited spermatogenesis with a broad inflammatory response in seminiferous tubules and led to the loss of spermatogenic epithelial cells. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) revealed that Dmrt1 positively regulated the expression of Spry1, an inhibitory protein of the receptor tyrosine kinase (RTK) signaling pathway. Furthermore, immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP) analysis indicated that SPRY1 binds to nuclear factor kappa B1 (NF-κB1) to prevent nuclear translocation of p65, inhibit activation of NF-κB signaling, prevent excessive inflammatory reaction in the testis, and protect the integrity of the blood-testis barrier. In view of this newly identified Dmrt1- Spry1-NF-κB axis mechanism in the regulation of testicular immune homeostasis, our study opens new avenues for the prevention and treatment of male reproductive diseases in humans and livestock.

Fluorine-Containing Covalent Organic Frameworks: Synthesis and Application.

Covalent organic frameworks (COFs) are a type of crystalline porous polymers that possess ordered structures and eternal pores. Because of their unique structural characteristics and diverse functional groups, COFs have been used in various application fields, such as adsorption, catalysis, separation, ion conduction, and energy storage. Among COFs, the fluorine-containing COFs (fCOFs) have been developed for special applications by virtue of special physical and chemical properties resulting from fluorine element, which is a nonmetallic halogen element and possesses strong electronegativity. In the organic chemistry field, introducing fluorine into chemicals enables those chemicals to exhibit many interesting properties, and fluorine chemistry increasingly plays an important role in the history of chemical development. The introduction of fluorine in COFs can enhance the crystallinity, porosity, and stability of COFs, making COFs having superior performances and some new applications. In this review, the synthesis and application of fCOFs are systematically summarized. The application involves photocatalytic production of hydrogen peroxide, photocatalytic water splitting, electrocatalytic CO2 reduction, adsorption for different substances (H2 , pesticides, per-/polyfluoroalkyl substances, polybrominated diphenyl ethers, bisphenols, and positively charged organic dye molecules), oil-water separation, energy storage (e.g., zinc-ion batteries, lithium-sulfur batteries), and proton conduction. Perspectives of remaining challenges and possible directions for fCOFs are also discussed.

Porous organic polymers for electrocatalysis.

Porous organic polymers (POPs) composed of organic building units linked via covalent bonds are a class of lightweight porous network materials with high surface areas, tuneable pores, and designable components and structures. Owing to their well-preserved characteristics in terms of structure and composition, POPs applied as electrocatalysts have shown promising activity and achieved considerable advances in numerous electrocatalytic reactions, including the hydrogen evolution reaction, oxygen evolution reaction, oxygen reduction reaction, CO2 reduction reaction, N2 reduction reaction, nitrate/nitrite reduction reaction, nitrobenzene reduction reaction, hydrogen oxidation reaction, and benzyl alcohol oxidation reaction. Herein, we present a systematic overview of recent advances in the applications of POPs in these electrocatalytic reactions. The synthesis strategies, specific active sites, and catalytic mechanisms of POPs are summarized in this review. The fundamental principles of some electrocatalytic reactions are also concluded. We further discuss the current challenges of and perspectives on POPs for electrocatalytic applications. Meanwhile, the possible future directions are highlighted to afford guidelines for the development of efficient POP electrocatalysts.

Synergistic Catalysis of Ionic Liquid-Decorated Covalent Organic Frameworks with Polyoxometalates for CO2 Cycloaddition Reaction under Mild Conditions.

The cycloaddition of carbon dioxide (CO2) with epoxides to yield highly value-added cyclic carbonates is an effective way to chemically utilize and convert CO2. Here, a heterogeneous catalyst of imidazole ionic liquid-decorated covalent organic framework with polyoxometalates (POM@ImTD-COF) was constructed by the covalent modification of ionic liquids to COFs and the electrostatic interaction between POMs and ionic liquids. The obtained POM@ImTD-COF shows high catalytic activity for CO2 cycloaddition reaction under mild conditions (1 atm and 80 °C) in the presence of a co-catalyst, and the catalytic activity of POM@ImTD-COF has no obvious decrease during reusing five times. The excellent catalytic performance is mainly attributed to the synergistic effect of ionic liquids, POMs, and COFs. In the cycloaddition process, ionic liquids and the co-catalyst weaken the C-O bond of epoxides and promote the ring opening of epoxides. POMs as the Lewis acids facilitate the insertion of CO2 to form reaction intermediates. The multiple activation effect of ionic liquids and POMs together with the CO2 adsorption effect and well-dispersed active sites in COFs contribute to the remarkable catalytic performance.

Melatonin relieves heat-induced spermatocyte apoptosis in mouse testes by inhibition of ATF6 and PERK signaling pathways.

Normal spermatogenic processes require the scrotal temperature to be lower than that of the body as excessive heat affects spermatogenesis in the testes, reduces sperm quality and quantity, and even causes infertility. Endoplasmic reticulum stress (ERS) is a crucial factor in many pathologies. Although several studies have linked ERS to heat stress, researchers have not yet determined which ERS signaling pathways contribute to heat-induced testicular damage. Melatonin activates antioxidant enzymes, scavenges free radicals, and protects the testes from inflammation; however, few studies have reported on the influence of melatonin on heat-induced testicular damage. Using a murine model of testicular hyperthermia, we observed that heat stress causes both ERS and apoptosis in the testes, especially in the spermatocytes. These observations were confirmed using the mouse spermatocyte cell line GC2, where the Atf6 and Perk signaling pathways were activated during heat stress. Knockout of the above genes effectively reduced spermatocyte damage caused by heat stress. Pretreatment with melatonin alleviated heat-induced apoptosis by inhibiting the Atf6 and Perk signaling pathways. This mitigation was dependent on the melatonin receptors. In vivo experiments verified that melatonin treatment relieved heat-induced testicular damage. In conclusion, our results demonstrated that ATF6 and PERK are important mediators for heat-induced apoptosis, which can be prevented by melatonin treatment. Thus, our study highlights melatonin as a potential therapeutic agent in mammals for subfertility/infertility induced by testicular hyperthermia.

Single-cell RNA sequencing reveals atlas of dairy goat testis cells.

Single-cell RNA sequencing (scRNA-seq) is useful for exploring cell heterogeneity. For large animals, however, little is known regarding spermatogonial stem cell (SSC) self-renewal regulation, especially in dairy goats. In this study, we described a high-resolution scRNA-seq atlas derived from a dairy goat. We identified six somatic cell and five spermatogenic cell subtypes. During spermatogenesis, genes with significantly changed expression were mainly enriched in the Notch, TGF-ß, and Hippo signaling pathways as well as the signaling pathway involved in the regulation of stem cell pluripotency. We detected and screened specific candidate marker genes ( TKTL1 and AES) for spermatogonia. Our study provides new insights into goat spermatogenesis and the development of testicular somatic cells.

Capacity analysis of oceanic channels with localized Lommel-Gaussian vortex beams.

The correlation function of localized Lommel-Gaussian vortex beams is obtained in oceanic turbulence and used to estimate the channel capacity of underwater wireless optical communication systems (UWOCS). The effects of laser source and oceanic turbulence on the channel capacity are discussed. Results show that the choices of appropriate light parameters, such as input pulse half-width, beam waist, and orbital angular momentum number, are essential to achieve high channel capacity in UWOCS. Another important factor that affects channel capacity is oceanic turbulence. Scaling analysis shows that inner scale has a more significant effect on the channel capacity than the outer scale does.

Accurate Correlation Modeling between Wind Speed and Bridge Girder Displacement Based on a Multi-Rate Fusion Method.

Wind action is one of the environmental actions that has significant static and dynamic effects on long-span bridges. The lateral wind speed is the main factor affecting the lateral displacement of the main girder of the bridge. The main objective of the paper is to use the improved multi-rate fusion method to correct the monitoring data so that accurate correlation modeling of wind speed-displacement can be achieved. Two Kalman gain coefficients are introduced to improve the traditional multi-rate fusion method. The fusion method is verified by the results of simulated data analysis in time domain and frequency domain. Then, the improved multi-rate fusion method is used to fuse the monitoring lateral displacement and acceleration data of a bridge under strong wind action. The corrected lateral wind speed and displacement data is further applied to establish the correlation model through the linear regression. The improved multi-rate fusion method can overcome the inaccuracy of the high frequency stage of a Global Positioning System (GPS) sensor and the low frequency stage of acceleration sensor. The correlation coefficient of wind speed-displacement after fusion increases and the confidence interval width of regression model decreases, which indicates that the accuracy of the correlation model between wind speed and displacement is improved.

FeCoP2 Nanoparticles Embedded in N and P Co-doped Hierarchically Porous Carbon for Efficient Electrocatalytic Water Splitting.

The design and synthesis of low-cost and efficient bifunctional electrocatalysts for water splitting are critical and challenging. Hereby, a bimetallic phosphide embedded in a N and P co-doped porous carbon (FeCoP2@NPPC) material was synthesized by using sustainable biomass-derived N- and P-containing carbohydrates and non-noble metal salts as precursors. The obtained material exhibits good catalytic activities in hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and overall water splitting. The bimetallic alloy phosphide (FeCoP2) is the active site for electrocatalysis. Theoretical calculation indicates that the sub-layer Fe atoms and top-layer Co atoms in FeCoP2 exhibit a synergistic effect for enhanced electrocatalytic performance. The carbon matrix around the FeCoP2 can prevent the corrosion during the catalytic reactions. The hierarchically porous structure of the FeCoP2@NPPC material can promote the transfer of electrons and electrolyte, and increase the contact area of the active sites and electrolytes. N- and P-containing functionalities improve the wetting and conductivity properties of the porous carbon. Due to the synergistic effects, FeCoP2@NPPC requires a low overpotential of 114 and 150 mV at the current density of 10 mA cm-2 for HER in 0.5 M H2SO4 and 1.0 M KOH, and an overpotential of 236 mV for OER in 1.0 M KOH solution, which are much lower than those of FeP@NPPC and CoP@NPPC. Based on the density functional theory calculation, FeCoP2 yields the smallest Gibbs free energy change of rate-determining step among the samples, which leads to better electrochemical performances. In addition, when FeCoP2@NPPC was used as a bifunctional catalyst in water splitting, the electrolyzer needed a low voltage of 1.60 V to deliver the current density of 10 mA cm-2. Furthermore, this work provides a strategy for preparing sustainable, stable, and highly active electrocatalysts for water splitting.

Dmrt1 regulates the immune response by repressing the TLR4 signaling pathway in goat male germline stem cells.

Double sex and mab-3-related transcription factor 1 (Dmrt1), which is expressed in goat male germline stem cells (mGSCs) and Sertoli cells, is one of the most conserved transcription factors involved in sex determination. In this study, we highlighted the role of Dmrt1 in balancing the innate immune response in goat mGSCs. Dmrt1 recruited promyelocytic leukemia zinc finger (Plzf), also known as zinc finger and BTB domain-containing protein 16 (Zbtb16), to repress the Toll-like receptor 4 (TLR4)-dependent inflammatory signaling pathway and nuclear factor (NF)-κB. Knockdown of Dmrt1 in seminiferous tubules resulted in widespread degeneration of germ and somatic cells, while the expression of proinflammatory factors were significantly enhanced. We also demonstrated that Dmrt1 stimulated proliferation of mGSCs, but repressed apoptosis caused by the immune response. Thus, Dmrt1 is sufficient to reduce inflammation in the testes, thereby establishing the stability of spermatogenesis and the testicular microenvironment.

N-doped graphitic carbon shell-encapsulated FeCo alloy derived from metal-polyphenol network and melamine sponge for oxygen reduction, oxygen evolution, and hydrogen evolution reactions in alkaline media.

Exploiting low cost and durable electrocatalysts with high efficiency for oxygen reduction reaction (ORR), oxygen evolution reaction (OER), and hydrogen evolution reaction (HER) is of great significance for energy conversion and storage applications. Herein, a hybrid electrocatalyst of FeCo alloy nanoparticles embedded in a porous N-doped carbon was prepared via a pyrolysis process of low-cost melamine sponge and mass-produced metal-polyphenol network. Benefting from the metal coordination of metal-polyphenol network and abundant N source of melamine sponge, the metal-N moiety and FeCo alloy nanoparticles (wtih a diameter around 50 nm) encapsulated in a N-doped graphene-like carbon layer were formed in-situ. Such intimate integration of graphene-like carbon-encapsulated FeCo alloys, metal-N active species, and porous structure is conducive to improve the catalytic activity and increase the catalytic durability in alkaline media. As a consequence, the as-prepared electrocatalyst exhibits the pronounced activity toward ORR, OER, and HER simultaneously under alkaline condition, particularly on the performances of potential, stability, and methanol tolerance.

Functional Characterization and Structural Basis of an Efficient Di-C-glycosyltransferase from Glycyrrhiza glabra.

A highly efficient di-C-glycosyltransferase GgCGT was discovered from the medicinal plant Glycyrrhiza glabra. GgCGT catalyzes a two-step di-C-glycosylation of flopropione-containing substrates with conversion rates of >98%. To elucidate the catalytic mechanisms of GgCGT, we solved its crystal structures in complex with UDP-Glc, UDP-Gal, UDP/phloretin, and UDP/nothofagin, respectively. Structural analysis revealed that the sugar donor selectivity was controlled by the hydrogen-bond interactions of sugar hydroxyl groups with D390 and other key residues. The di-C-glycosylation capability of GgCGT was attributed to a spacious substrate-binding tunnel, and the G389K mutation could switch di- to mono-C-glycosylation. GgCGT is the first di-C-glycosyltransferase with a crystal structure, and the first C-glycosyltransferase with a complex structure containing a sugar acceptor. This work could benefit the development of efficient biocatalysts to synthesize C-glycosides with medicinal potential.

Hollow N-doped Carbon Polyhedrons with Hierarchically Porous Shell for Confinement of Polysulfides in Lithium-Sulfur Batteries.

Herein, hollow N-doped carbon polyhedrons with hierarchical pores were fabricated by etching ZIF-8 crystals and were first used as the host of sulfur for lithium-sulfur batteries. This host possesses both micropores and mesopores, and inner wide cavities, which enable the sulfur to effectively immerse into the polyhedrons without obstacles and simultaneously restrict the escaping of polysulfides by outer carbon shell and abundant N sites. Hence, the polyhedron host combines the physical confinement and chemical interaction for polysulfides by virtue of the unique architecture. As a result, the hierarchically porous polyhedron enables a sulfur content of 72 wt% and achieves a faster polysulfide trapping and better electrochemical performance than the ZIF-8-derived microporous host at the sulfur loading of 1 and 5 mg cm-2.

Effects of liraglutide, metformin and gliclazide on body composition in patients with both type 2 diabetes and non-alcoholic fatty liver disease: A randomized trial.

AIMS/INTRODUCTION: To compare the effects of gliclazide, liraglutide and metformin on body composition in patients with type 2 diabetes mellitus with non-alcoholic fatty liver disease. MATERIALS AND METHODS: A total of 85 patients were randomly allocated to receive gliclazide (n = 27), liraglutide (n = 29) or metformin (n = 29) monotherapy for 24 weeks. Body composition was measured using dual-energy X-ray absorptiometry. RESULTS: Liraglutide and metformin reduced total, trunk, limb, android and gynoid fat mass; this also led to weight reduction. However, gliclazide treatment produced no significant changes in weight or fat mass, likely because reductions in fat mass were concomitant with increases in lean tissue mass. Blood glucose concentrations and glycated hemoglobin levels improved in all treatment arms; levels of the latter were lower in patients treated with liraglutide and metformin. Serum alanine aminotransferase concentrations decreased in all treatment arms, whereas serum aspartate aminotransferase concentrations were reduced only by liraglutide and metformin. In all patients, weight loss and total, trunk, limb, and android fat mass reductions were positively correlated with decreases in serum alanine aminotransferase and aspartate aminotransferase levels, whereas reductions in waist circumference were positively correlated with lower serum alanine aminotransferase levels. CONCLUSIONS: Compared with gliclazide, liraglutide and metformin monotherapies result in greater weight loss, reductions in body fat mass, and better blood glucose control among type 2 diabetes mellitus patients with non-alcoholic fatty liver disease. Reductions in weight, fat mass and waist circumference favorably affect hepatic function.

Metal-Organic Gel-Derived Fex Oy /Nitrogen-Doped Carbon Films for Enhanced Lithium Storage.

The development of cost-effective and flexible electrodes is demanding in the field of energy storage. Herein, flexible Fex Oy /nitrogen-doped carbon films (Fex Oy /NC-MOG) are prepared by facile electrospinning of Fe-based metal-organic gels (MOGs) followed by high-temperature carbonization. This approach allows the even mixing of fragile coordination polymers with polyacrylonitrile into flexible films while reserving the structural characteristics of coordination polymers. After thermal treatment, Fex Oy /NC-MOG films possess uniformly distributed Fex Oy nanoparticles and larger accessible surface areas than traditional Fex Oy -NC films without MOG. Taking advantage of the unique structure, Fex Oy /NC-MOG exhibits a superior rate performance (449.8 mA h g-1 at 5000 mA g-1 ) and long cycle life (629.3 mA h g-1 after 500 cycles at 1000 mA g-1 ) when used as additive-free anodes in lithium-ion batteries.

Dietary Total Prenylflavonoids from the Fruits of Psoralea corylifolia L. Prevents Age-Related Cognitive Deficits and Down-Regulates Alzheimer's Markers in SAMP8 Mice.

Alzheimer's disease (AD) is a serious threat for the aging society. In this study, we examined the preventive effect of the total prenylflavonoids (TPFB) prepared from the dried fruits of Psoralea corylifolia L., using an age-related AD mouse model SAMP8. We found that long-term dietary TPFB at 50 mg/kg·day significantly improved cognitive performance of the SAMP8 mice in Morris water maze tests, similar to 150 mg/kg·day of resveratrol, a popular neuro-protective compound. Furthermore, TPFB treatment showed significant improvements in various AD markers in SAMP8 brains, which were restored to near control levels of the normal mice, SAMR1. TPFB significantly reduced the level of amyloid ß-peptide 42 (Aß42), inhibited hyperphosphorylation of the microtubule-associated protein Tau, induced phosphorylation of Ser9 of the glycogen synthase kinase 3ß (GSK-3ß), and decreased the expression of the proinflammatory cytokines TNFα, IL-6, and IL-1ß. Finally, TPFB also markedly reduced the level of serum derivatives of reactive oxygen metabolites (d-ROMs), a biomarker of oxidative stress in vivo. These results showed that dietary TPFB could effectively prevent age-related cognitive deficits and AD-like neurobiochemical changes, and may have a potential role in the prevention of Alzheimer's disease.

Bimetallic metal-organic framework derived Co3O4-CoFe2O4 composites with different Fe/Co molar ratios as anode materials for lithium ion batteries.

Developing high-performance electrode materials to replace a traditional graphite electrode is critical for the commercialization of lithium ion batteries, which however still remains a great challenge. Herein, we report a suitable method to synthesize a series of well-dispersed nanostructured Co3O4-CoFe2O4 composites (CCFs) from bimetallic metal-organic frameworks (BiMOFs) with varied Fe3+/Co2+ molar ratios. When used as anodes for lithium ion batteries, the CCF-12 composite exhibits a maximum initial discharge capacity of 1328 mA h g-1, a reversible capacity of 940 mA h g-1 at 100 mA g-1 after 80 cycles, and a better rate capability in comparison with those of pure Co3O4 and other CCF composites. The well-dispersed structure and small particle size are believed to mainly contribute to the outstanding electrochemical performance of CCF-12 electrodes.