Construction of Highly Porous and Robust Hydrogen-Bonded Organic Framework for High-Capacity Clean Energy Gas Storage.

Development of highly porous and robust HOFs for high-pressure methane and hydrogen storage remains a grand challenge due to the fragile nature of hydrogen bonds. Herein, we report a strategy of constructing double-walled framework to target highly porous and robust HOF (ZJU-HOF-5a) for extraordinary CH4 and H2 storage. ZJU-HOF-5a features a minimized twofold interpenetration with double-walled structure, in which multiple supramolecular interactions are existed between the interpenetrated walls. This structural configuration can notably enhance the framework robustness while maintaining its high porosity, affording one of the highest gravimetric and volumetric surface areas of 3102 m2 g-1 and 1976 m2 cm-3 among the reported HOFs so far. ZJU-HOF-5a exhibits an extremely high volumetric H2 uptake of 43.6 g L-1 at 77 K/100 bar and working capacity of 41.3 g L-1 under combined swing conditions, and also impressive methane storage performance with a 5-100 bar working capacity of 187 (or 159) cm3 cm-3 at 270 K (or 296 K). SCXRD studies on CH4-loaded ZJU-HOF-5a reveal that abundant supramolecular binding sites combined with ultrahigh porosities account for its high CH4 storage capacities. Combined with high stability, super-hydrophobicity, and easy-recovery, ZJU-HOF-5a is placed among the most promising materials for H2 and CH4 storage applications.

Clinical research progress on acupuncture for the treatment of otogenic vertigo.

Otogenic vertigo is a common disorder that affects the vestibular system, which often results in considerable discomfort and impaired daily functioning. Traditional Chinese medicine (TCM), including acupuncture and moxibustion, has been historically utilized to manage the symptoms of vertigo. However, the effectiveness and methodology of these treatments have rarely been investigated in the medical literature. This study reviews the existing literature on the point selection, method, and therapeutic effect of acupuncture and moxibustion to provide a reference for the TCM treatment of otogenic vertigo. A literature search was performed using the PubMed search engine. The terms used included otogenic vertigo, acupuncture treatment, and acupuncture point selection. A total of 34 relevant articles were retrieved from PubMed. These suggest that the clinical treatment of otogenic vertigo should consider the functions of zang-fu organs and meridians and select different acupuncture treatment methods according to syndrome differentiation based on the difference between deficiency and excess. Acupuncture and moxibustion therapy should be based on acupoint selection, considering the syndrome differentiation, supplemented with experience. The treatment of otogenic vertigo with acupuncture and moxibustion refers to the selection of appropriate acupuncture methods under the guidance of TCM theory and following the principles of syndrome, disease, and meridian differentiation. Common acupuncture methods include body acupuncture, auricular acupuncture, scalp acupuncture, acupoint injection, electroacupuncture, and moxibustion. There are many acupuncture and moxibustion acupoints selected for the treatment of otogenic vertigo. Individualized treatment according to the patient's specific condition is effective and safe, which can help to improve the patient's vertigo symptoms and cerebral blood perfusion.

Inhibition of the p62-Nrf2-GPX4 Pathway Confers Sensitivity to Butachlor-Induced Splenic Macrophage Ferroptosis.

Butachlor is widely used in agriculture around the world and therefore poses environmental and public health hazards due to persistent and poor biodegradability. Ferroptosis is a type of iron-mediated cell death controlled by glutathione (GSH) and GPX4 inhibition. P62 is an essential autophagy adaptor that regulates Keap1 to activate nuclear factor erythroid 2-related factor 2 (Nrf2), which effectively suppresses lipid peroxidation, thereby relieving ferroptosis. Here, we found that butachlor caused changes in splenic macrophage structure, especially impaired mitochondrial morphology with disordered structure, which is suggestive of the occurrence of ferroptosis. This was further confirmed by the detection of iron metabolism, the GSH system, and lipid peroxidation. Mechanistically, butachlor suppressed the protein level of p62 and promoted Keap1-mediated degradation of Nrf2, which results in decreased GPX4 expression and accelerated splenic macrophage ferroptosis. These findings suggest that targeting the p62-Nrf2-GPX4 signaling axis may be a promising strategy for treating inflammatory diseases.

AQP1 Deficiency Drives Phthalate-Induced Epithelial Barrier Disruption through Intestinal Inflammation.

Di-2-ethylhexyl phthalate (DEHP) is frequently used as a plasticizer to enhance the plasticity and durability of agricultural products, which pose adverse effects to human health and the environment. Aquaporin 1 (AQP1) is a main water transport channel protein and is involved in the maintenance of intestinal integrity. However, the impact of DEHP exposure on gut health and its potential mechanisms remain elusive. Here, we determined that DEHP exposure induced a compromised duodenum structure, which was concomitant with mitochondrial structural injury of epithelial cells. Importantly, DEHP exposure caused duodenum inflammatory epithelial cell damage and strong inflammatory response accompanied by activating the TLR4/MyD88/NF-κB signaling pathway. Mechanistically, DEHP exposure directly inhibits the expression of AQP1 and thus leads to an inflammatory response, ultimately disrupting duodenum integrity and barrier function. Collectively, our findings uncover the role of AQP1 in phthalate-induced intestinal disorders, and AQP1 could be a promising therapeutic approach for treating patients with intestinal disorders or inflammatory diseases.

Revision of the Genus Rhagastis Rothschild & Jordan, 1903 (Lepidoptera: Sphingidae) from China, Based on Morphological and Phylogenetic Analyses.

Here, the taxonomy of the genus Rhagastis Rothschild & Jordan, 1903 (Lepidoptera, Sphingidae, Macroglossinae, Macroglossini) from China is revised based on differences in wing morphology, male and female genitalia, and the phylogenetic relationship of the DNA barcodes. Subspecies of Rhagastis albomarginatus (Rothschild, 1894) and R. castor (Walker, 1856) are treated as "good" species, namely Rhagastis dichroae Mell, 1922 stat. nov.; R. everetti Rothschild & Jordan, 1903 stat. nov.; R. aurifera (Butler, 1875) stat. rev.; R. chinensis Mell, 1922 stat. nov.; R. formosana Clark, 1925 stat. nov.; and R. jordani Oberthür, 1904 stat. rev. The distribution maps, biological notes, and ecological records of the genus Rhagastis Rothschild & Jordan, 1903 from China are given, and a species inventory of genus Rhagastis in the world is also included.

(C4H6N3O)(HSO4): A Cytosinium Bisulfate with Large Birefringence and Moderate Second Harmonic Generation Effect Produced via Combining a Promising Planar Nonlinear Optical-Active Motif with a Tetrahedral Group.

Investigating novel nonlinear optical (NLO) active units serves as a valuable method for broadening the research landscape of NLO materials. This study showcases the potential of the cytosinium cation (C4H6N3O)+ as a novel NLO-active motif through theoretical calculations. The title compound exhibited a wide band gap of 3.85 eV, along with a moderate second harmonic generation (SHG) response of 1.65 times that of KH2PO4 (KDP) and significant birefringence of 0.47. Its exceptional optical properties are primarily attributed to the synergy interaction between cations and anionic groups in the asymmetric unit.

Novel quinoxaline analogs as telomeric G-quadruplex ligands exert antitumor effects related to enhanced immunomodulation.

G-quadruplexes (G4s) are commonly formed in the G-rich strand of telomeric DNA. Ligands targeting telomeric G4 induce DNA damage and telomere dysfunction, which makes them potential antitumor drugs. New telomeric G4 ligands with drug-likeness are still needed to be exploited, especially with their antitumor mechanisms thoroughly discussed. In this study, a novel series of quinoxaline analogs were rationally designed and synthesized. Among them, R1 was the most promising ligand for its cytotoxic effects on tumor cells and stabilizing ability with telomeric G4. Cellular assays illustrated that R1 stabilized G4 and induced R-loop accumulation in the telomeric regions, subsequently triggering DNA damage responses, cell cycle arrest in G2/M phase, apoptosis and antiproliferation. Moreover, R1 evoked immunogenic cell death (ICD) in tumor cells, which promoted the maturation of bone marrow derived dendritic cells (BMDCs). In breast cancer mouse model, R1 exhibited a significant decrease in tumor burden through the immunomodulatory effects, including the increase of CD4+ and CD8+ T cells in tumors and cytokine levels in sera. Our research provides a new idea that targeting telomeric G4 induces DNA damage responses, causing antitumor effects both in vitro and in vivo, partially due to the enhancement of immunomodulation.

SLC7A11 as a therapeutic target to attenuate phthalates-driven testosterone level decline in mice.

INTRODUCTION: Phthalates exposure is a major public health concern due to the accumulation in the environment and associated with levels of testosterone reduction, leading to adverse pregnancy outcomes. However, the relationship between phthalate-induced testosterone level decline and ferroptosis remains poorly defined. OBJECTIVES: Herein, we aimed to explore the mechanisms of phthalates-induced testosterone synthesis disorder and its relationship to ferroptosis. METHODS: We conducted validated experiments in vivo male mice model and in vitro mouse Leydig TM3 cell line, followed by RNA sequencing and metabolomic analysis. We evaluated the levels of testosterone synthesis-associated enzymes and ferroptosis-related indicators by using qRT-PCR and Western blotting. Then, we analyzed the lipid peroxidation, ROS, Fe2+ levels and glutathione system to confirm the occurrence of ferroptosis. RESULTS: In the present study, we used di (2-ethylhexyl) phthalate (DEHP) to identify ferroptosis as the critical contributor to phthalate-induced testosterone level decline. It was demonstrated that DEHP caused glutathione metabolism and steroid synthesis disorders in Leydig cells. As the primary metabolite of DEHP, mono-2-ethylhexyl phthalate (MEHP) triggered testosterone synthesis disorder accompanied by a decrease in the expression of solute carri1er family 7 member 11 (SLC7A11) protein. Furthermore, MEHP synergistically induced ferroptosis with Erastin through the increase of intracellular and mitochondrial ROS, and lipid peroxidation production. Mechanistically, overexpression of SLC7A11 counteracts the synergistic effect of co-exposure to MEHP-Erastin. CONCLUSION: Our research results suggest that MEHP does not induce ferroptosis but synergizes Erastin-induced ferroptosis. These findings provide evidence for the role of ferroptosis in phthalates-induced testosterone synthesis disorder and point to SLC7A11 as a potential target for male reproductive diseases. This study established a correlation between ferroptosis and phthalates cytotoxicity, providing a novel view point for mitigating the issue of male reproductive disease and "The Global Plastic Toxicity Debt".

Xylarkarynone A and B: Two Bioactive Eremophilane Sesquiterpenes from Xylaria sp. HHY-2.

A new compound xylarkarynone A (1), a first reported natural product compound xylarkarynone B (2) and eight known compounds (3-10) were isolated from Xylaria sp. HHY-2. Their structures were elucidated by spectroscopic methods, DP4+ probability analyses and electronic circular dichroism (ECD) calculations. The bioactivities of isolated compounds were assayed. Compound 1 exhibited obvious activity against A549 cells with an IC50 value of 6.12±0.28 µM. Additionally, compound 1 showed moderate antifungal activities against Plectosphaerella cucumerina and Aspergillus niger with minimum inhibitory concentrations (MICs) of both 16 µg/mL, which was at the same grade with positive control nystatin. Most compounds exhibited varying degrees of inhibitory activity against P. cucumerina, indicating that Xylaria sp. has potential as inhibitors against P. cucumerina.

Multilevel Information Encryption Based on Thermochromic Perovskite Microcapsules via Orthogonal Photic and Thermal Stimuli Responses.

Increasing modal variations of stimulus-responsive materials ensure the high capacity and confidentiality of information storage and encryption systems that are crucial to information security. Herein, thermochromic perovskite microcapsules (TPMs) with dual-variable and quadruple-modal reversible properties are designed and prepared on the original oil-in-fluorine (O/F) emulsion system. The TPMs respond to the orthogonal variations of external UV and thermal stimuli in four reversible switchable modes and exhibit excellent thermal, air, and water stability due to the protection of perovskites by the core-shell structure. Benefiting from the high-density information storage TPMs, multiple information encryptions and decryptions are demonstrated. Moreover, a set of devices are assembled for a multilevel information encryption system. By taking advantage of TPMs as a "private key" for decryption, the signal can be identified as the corresponding binary ASCII code and converted to the real message. The results demonstrate a breakthrough in high-density information storage materials as well as a multilevel information encryption system based on switchable quadruple-modal TPMs.

Supramolecular Entanglement in a Hydrogen-Bonded Organic Framework Enables Flexible-Robust Porosity for Highly Efficient Purification of Natural Gas.

The development of porous materials with flexible-robust characteristics shows some unique advantages to target high performance for gas separation, but remains a daunting challenge to achieve so far. Herein, we report a carboxyl-based hydrogen-bonded organic framework (ZJU-HOF-8a) with flexible-robust porosity for efficient purification of natural gas. ZJU-HOF-8a features a four-fold interpenetrated structure with dia topology, wherein abundant supramolecular entanglements are formed between the adjacent subnetworks through weak intermolecular hydrogen bonds. This structural configuration could not only stabilize the whole framework to establish the permanent porosity, but also enable the framework to show some flexibility due to its weak intermolecular interactions (so-called flexible-robust framework). The flexible-robust porosity of ZJU-HOF-8a was exclusively confirmed by gas sorption isotherms and single-crystal X-ray diffraction studies, showing that the flexible pore pockets can be opened by C3H8 and n-C4H10 molecules rather by C2H6 and CH4. This leads to notably higher C3H8 and n-C4H10 uptakes with enhanced selectivities than C2H6 over CH4 under ambient conditions, affording one of the highest n-C4H10/CH4 selectivities. The gas-loaded single-crystal structures coupled with theoretical simulations reveal that the loading of n-C4H10 can induce an obvious framework expansion along with pore pocket opening to improve n-C4H10 uptake and selectivity, while not for C2H6 adsorption. This work suggests an effective strategy of designing flexible-robust HOFs for improving gas separation properties.

[C(NH2)3][B(C2O2H4)2]: An Organic-Inorganic Hybrid Borate Containing Nonlinear-Optical Active Unit [B(C2O2H4)2]- with Solar-Blind-Region Optical Nonlinearity.

We herein report an unprecedented organic-inorganic hybrid borate incorporating a novel nonlinear-optical (NLO) active unit, namely, [C(NH2)3][B(C2O2H4)2]. The novel NLO active unit was derived from the condensation reaction between two glycol molecules and one (BO4)5- group. The title compound exhibits a moderate second-harmonic-generation effect (0.7 × KDP), a significant band gap (5.76 eV), and a suitable birefringence (0.078 at 550 nm). The optical properties are determined by the synergistic interaction between the C(NH2)3+ cation and the [B(C2O2H4)2]- group, as indicated by theoretical calculations.

Prognostic value of GLIM-defined malnutrition in combination with hand-grip strength or gait speed for the prediction of postoperative outcomes in gastric cancer patients with cachexia.

BACKGROUND: Cancer cachexia is associated with impaired functional and nutritional status and worse clinical outcomes. Global Leadership Initiative in Malnutrition (GLIM) consensus recommended the application of GLIM criteria to diagnose malnutrition in patients with cachexia. However, few previous study has applied the GLIM criteria in patients with cancer cachexia. METHODS: From July 2014 to May 2019, patients who were diagnosed with cancer cachexia and underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index was measured using abdominal computed tomography (CT) images at the third lumbar vertebra (L3) level. Hand-grip strength and 6-meters gait speed were measured before surgery. RESULTS: A total of 356 patients with cancer cachexia were included in the present study, in which 269 (75.56%) were identified as having malnutrition based on the GLIM criteria. GLIM-defined malnutrition alone did not show significant association with short-term postoperative outcomes, including complications, costs or length of postoperative hospital stays. The combination of low hand-grip strength or low gait speed with GLIM-defined malnutrition led to a significant predictive value for these outcomes. Moreover, low hand-grip strength plus GLIM-defined malnutrition was independently associated with postoperative complications (OR 1.912, 95% CI 1.151-3.178, P = 0.012). GLIM-defined malnutrition was an independent predictive factor for worse OS (HR 2.310, 95% CI 1.421-3.754, P = 0.001) and DFS (HR 1.815, 95% CI 1.186-2.779, P = 0.006) after surgery. The addition of low hand-grip strength or low gait speed to GLIM-defined malnutrition did not increase its predictive value for survival. CONCLUSION: GLIM-defined malnutrition predicted worse long-term survival in gastric cancer patients with cachexia. Gait speed and hand-grip strength added prognostic value to GLIM-defined malnutrition for the prediction of short-term postoperative outcomes, which could be incorporated into preoperative assessment protocols in patients with cancer cachexia.

[C(NH2)3]6Mo7O24: A Guanidinium Molybdate as a UV Nonlinear Optical Crystal with Large Birefringence.

The key to searching novel nonlinear optical (NLO) crystals was effectively combining the NLO-active units to obtain a noncentrosymmetric structure. Nevertheless, the present predicament lies in the growing challenge of discovering novel crystals within conventional inorganic frameworks that surpass the properties of the current NLO materials. In view of this, researchers expanded their research focus to the organic-inorganic hybridization system; it is foreseeable to concentrate the advantages from several kinds of NLO-active units to acquire novel NLO crystals with superior properties. We herein report an organic-inorganic hybrid molybdate crystal, namely, [C(NH2)3]6Mo7O24 (GMO). It was successfully obtained via combining inorganic NLO-active MoO6 octahedra and organic π-conjugated [C(NH2)3]+ groups. GMO demonstrates a moderate second-harmonic-generation response, specifically measuring about 1.3 times the value of KDP. Additionally, it exhibits a significant birefringence value of 0.203 at the wavelength of 550 nm and possesses a wide band gap of 3.31 eV. Theoretical calculations suggest that the optical properties of the GMO are primarily influenced by the synergy effect of [C(NH2)3]+ groups between MoO6 octahedra.

Phthalate drives splenic inflammatory response via activating HSP60/TLR4/NLRP3 signaling axis-dependent pyroptosis.

As the most produced phthalate, di-(2-ethylhexyl) phthalate (DEHP) is a widely environmental pollutant primarily used as a plasticizer, which cause the harmful effects on human health. However, the impact of DEHP on spleen and its underlying mechanisms are still unclear. Pyroptosis is a novel form of cell death induced by activating NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes and implicated in pathogenesis of numerous inflammatory diseases. The current study aimed to explore the impact of DEHP on immune inflammatory response in mouse spleen. In this study, the male ICR mice were treated with DEHP (200 mg/kg) for 28 days. Here, DEHP exposure caused abnormal pathohistological and ultrastructural changes, accompanied by inflammatory cells infiltration in mouse spleen. DEHP exposure arouse heat shock response that involves increase of heat shock proteins 60 (HSP60) expression. DEHP also elevated the expressions of toll-like receptor 4 (TLR4) and myeloid differentiation protein 88 (MyD88) proteins, as well as the activation of NF-κB pathway. Moreover, DEHP promoted NLRP3 inflammasome activation and triggered NLRP3 inflammasome-induced pyroptosis. Mechanistically, DEHP drives splenic inflammatory response via activating HSP60/TLR4/NLRP3 signaling axis-dependent pyroptosis. Our findings reveal that targeting HSP60-mediated TLR4/NLRP3 signaling axis may be a promising strategy for inflammatory diseases treatment.

Phthalates Induce Neurotoxicity by Disrupting the Mfn2-PERK Axis-Mediated Endoplasmic Reticulum-Mitochondria Interaction.

Di-(2-ethylhexyl) phthalate (DEHP), as the most common phthalate, has been extensively used as a plasticizer to improve the plasticity of agricultural products, which pose severe harm to human health. Mitochondrial dynamics and endoplasmic reticulum (ER) homeostasis are indispensable for maintaining mitochondria-associated ER membrane (MAM) integrity. In this study, we aimed to explore the effect of DEHP on the nervous system and its association with the ER-mitochondria interaction. Here, we showed that DEHP caused morphological changes, motor deficits, cognitive impairments, and blood-brain barrier disruption in the brain. DEHP triggered ER stress, which is mainly mediated by protein kinase R-like endoplasmic reticulum kinase (PERK) signaling. Moreover, DEHP-induced mitofusin-2 (Mfn2) downregulation results in imbalance of the mitochondrial dynamics. Interestingly, DEHP exposure impaired MAMs by inhibiting the Mfn2-PERK interaction. Above all, this study elucidates the disruption of the Mfn2-PERK axis-mediated ER-mitochondria interaction as a phthalate-induced neurotoxicity that could be potentially developed as a novel therapy for neurological diseases.

Combination Therapy with a TLR7 Agonist and a BRD4 Inhibitor Suppresses Tumor Growth via Enhanced Immunomodulation.

JQ-1 is a typical BRD4 inhibitor with the ability to directly fight tumor cells and evoke antitumor immunity via reducing the expression of PD-L1. However, problems arise with the development of JQ-1 in clinical trials, such as marked lymphoid and hematopoietic toxicity, leading to the investigation of combination therapy. SZU-101 is a TLR7 agonist designed and synthesized by our group with potent immunostimulatory activity. Therefore, we hypothesized that combination therapy of SZU-101 and JQ-1 would target innate immunity and adaptive immunity simultaneously, to achieve a better antitumor efficacy than monotherapy. In this study, the repressive effects of the combination administration on tumor growth and metastasis were demonstrated in both murine breast cancer and melanoma models. In 4T1 tumor-bearing mice, i.t. treatment with SZU-101 in combination with i.p. treatment with JQ-1 suppressed the growth of tumors at both injected and uninjected sites. Combination therapy increased M1/M2 ratio in TAMs, decreased PD-L1 expression and promoted the recruitment of activated CD8+ T cells in the TME. In summary, the improved therapeutic efficacy of the novel combination therapy appears to be feasible for the treatment of a diversity of cancers.

Photoinduced Triphenylphosphine and Iodide Salt Promoted Reductive Decarboxylative Coupling.

The transient electron donor-acceptor (EDA) complex has been an emerging area in the photoinduced organic synthesis field, generating radicals without exogenous transition-metal or organic dye-based photoredox catalysts. The catalytic platform to form suitable photoactive EDA complexes for photochemical reduction reactions remains underdeveloped. Herein, a general photoinduced reductive alkylation via the EDA complex strategy is described. A simple yet multifunctional system, triphenylphosphine and iodide salt, promotes the photoinduced decarboxylative hydroalkylation, and reductive defluorinative decarboxylative alkylation of trifluoromethyl alkenes, to access trifluoromethyl alkanes and gem-difluoroalkenes. Moreover, decarboxylative hydroalkylation can be applied to more kinds of electron-deficient alkenes as a general Giese addition reaction.

Tunable Low-Pressure Water Adsorption in Stable Multivariate Metal-Organic Frameworks for Boosting Water-Based Ultralow-Temperature-Driven Refrigeration.

The green water-based adsorption refrigeration is considered as a promising strategy to realize near-zero-carbon cooling applications. Although many metal-organic frameworks (MOFs) have been developed as water adsorbents, their cooling performance are commonly limited by the insufficient water uptakes below P/P0 = 0.2. Herein, the development of multivariate MOFs (MTV-MOFs) is reported to highly modulate and boost the low-pressure water uptake for improving coefficient of performance (COP) for refrigeration. Through ligand exchange in the pristine MIL-125-NH2 , a series of MTV-MOFs with bare nitrogen sites are designed and synthesized. The resulting MIL-125-NH2 /MD-5% exhibits the significantly improved water uptake of 0.39 g g-1 at 298 K and P/P0 = 0.2, which is three times higher than MIL-125-NH2 (0.12 g g-1 ) and comparable to some benchmark materials including KMF-1 (0.4 g g-1 ) and MIP-200 (0.36 g g-1 ). Combined with its low-temperature regeneration, fast sorption kinetics and high stability, MIL-125-NH2 /MD-5% achieves one of the highest COP values (0.8) and working capacities (0.24 g g-1 ) for refrig-2 under an ultralow-driven temperature of 65 °C, which are higher than some best-performing MOFs such as MIP-200 (0.74 and 0.11 g g-1 ) and KMF-2 (0.62 and 0.16 g g-1 ), making it among the best adsorbents for efficient ultralow-temperature-driven refrigeration.