miRNAs in treatment-resistant depression: a systematic review.

BACKGROUND: Treatment-resistant depression (TRD) is a condition in a subset of depressed patients characterized by resistance to antidepressant medications. The global prevalence of TRD has been steadily increasing, yet significant advancements in its diagnosis and treatment remain elusive despite extensive research efforts. The precise underlying pathogenic mechanisms are still not fully understood. Epigenetic mechanisms play a vital role in a wide range of diseases. In recent years, investigators have increasingly focused on the regulatory roles of miRNAs in the onset and progression of TRD. miRNAs are a class of noncoding RNA molecules that regulate the translation and degradation of their target mRNAs via interaction, making the exploration of their functions in TRD essential for elucidating their pathogenic mechanisms. METHODS AND RESULTS: A systematic search was conducted in four databases, namely PubMed, Web of Science, Cochrane Library, and Embase, focusing on studies related to treatment-resistant depression and miRNAs. The search was performed using terms individually or in combination, such as "treatment-resistant depression," "medication-resistant depression," and "miRNAs." The selected articles were reviewed and collated, covering the time period from the inception of each database to the end of February 2024. We found that miRNAs play a crucial role in the pathophysiology of TRD through three main aspects: 1) involvement in miRNA-mediated inflammatory responses (including miR-155, miR-345-5p, miR-146a, and miR-146a-5p); 2) influence on 5-HT transport processes (including miR-674,miR-708, and miR-133a); and 3) regulation of synaptic plasticity (including has-miR-335-5p,has-miR- 1292-3p, let-7b, and let-7c). Investigating the differential expression and interactions of these miRNAs could contribute to a deeper understanding of the molecular mechanisms underlying TRD. CONCLUSIONS: miRNAs might play a pivotal role in the pathogenesis of TRD. Gaining a deeper understanding of the roles and interrelations of miRNAs in TRD will contribute to elucidating disease pathogenesis and potentially provide avenues for the development of novel diagnostic and therapeutic strategies.

Activated Singlet Fission Dictated by Anti-Kasha Property in a Rylene Imide Dye.

A key challenge in the search of new materials capable of singlet fission (SF) arises from the primary energy conservation criterion, i.e., the energy of the triplet exciton has to be half that of the singlet (E(S1) ≥ 2E(T1)), which excludes most photostable organic materials from consideration and confines the design strategy to materials with low energy triplet states. One potential way to overcome this energy requirement and improve the triplet energy is to enable a SF channel from higher energy ("hot") excitonic states (Sn) in a process called activated SF. Herein, we demonstrate that efficient activated SF is achieved in a rylene imide-based derivative acenaphth[l, 2-a]acenaphthylene diimide (AADI). This process is enabled by an increase in the energy gap to greater than 1.0 eV between the S3 and S1 states due to the incorporation of an antiaromatic pentalene unit, which leads to the emergence of anti-Kasha properties in the isolated molecule. Transient spectroscopy studies show that AADI undergoes ultrafast SF from higher singlet excited states in thin film, with excitation wavelength-dependent SF yields. The SF yield of ∼200% is observed upon higher energy excitation, and long-lived free triplets persist on the µs time scale suggesting that AADI can be used in SF-enhanced devices. Our results suggest that enlarging the Sn-S1 energy gap is an effective way to turn on the activated SF channel and shed light on the development of novel, stable SF materials with high triplet energies.

Quantitative assessment of ecological risk from pollution source based on geostatistical analysis and APCS-MLR model.

The safety of human health and agricultural production depends on the quality of farmland soil. Risk assessment of heavy metal pollution sources could effectively reduce the hazard of soil pollution from various sources. This study has identified and quantitatively analyzed pollution sources with geostatistical analysis and the APCS-MLR model. The potential ecological risk index was combined with the APCS-MLR model which has quantitatively calculated the source contribution. The results revealed that As, Cr, Cd, Pb, Zn, and Cu were enriched in soil. Geostatistical analysis and the APCS-MLR model have apportioned four pollution sources. The Mn and Ni were attributed to natural sources; As and Cr were from agricultural activities; Cu and Zn were originated from natural sources; Cd and Pb were derived from atmospheric deposition. Atmospheric deposition and agricultural activities were the largest contributors to ecological risk of heavy metals in soil, which accounted for 56.21% and 36.01% respectively. Atmospheric deposition and agricultural activities are classified as priority sources of pollution. The combination of source analysis receptor model and risk assessment is an effective method to quantify source contribution. This study has quantified the ecological risks of soil heavy metals from different sources, which will provide a reliable method for the identification of primary harmfulness sources of pollution for future studies.

Litter quality and climate regulate the effect of invertebrates on litter decomposition in terrestrial and aquatic ecosystems: A global meta-analysis.

Although the exclusion effects of invertebrate decomposers on litter decomposition have been extensively studied in different experimental contexts, a thorough comparison of the exclusion effects of invertebrate decomposers with different body sizes on litter decomposition and its possible regulatory factors in terrestrial and aquatic ecosystems is still lacking. Here, through a meta-analysis of 1207 pairs of observations from 110 studies in terrestrial ecosystems and 473 pairs of observations from 60 studies in aquatic ecosystems, we found that invertebrate exclusion reduced litter decomposition rates by 36 % globally, 30 % in terrestrial ecosystems, and 44 % in aquatic ecosystems. At the global scale, the exclusion effects of macroinvertebrates and mesoinvertebrates on litter decomposition rates (reduced by 38 % and 36 %, respectively) were greater than those of the combination of macroinvertebrates and mesoinvertebrates (reduced by 30 %). In terrestrial and aquatic ecosystems, the effects of invertebrate exclusion on litter decomposition rates were mainly regulated by climate and initial litter quality, but the effects of invertebrate exclusion with different body sizes were regulated differently by climate, initial litter quality, and abiotic environmental variables. These findings will help us better understand the role of invertebrate decomposers in litter decomposition, especially for invertebrate decomposers with different body sizes, and underscore the need to incorporate invertebrate decomposers with different body sizes into dynamic models of litter decomposition to examine the potential effects and regulatory mechanisms of land-water-atmosphere carbon fluxes.

Formation mechanism of quinoa protein hydrolysate-EGCG complexes at different pH conditions and its effect on the protein hydrolysate-lipid co-oxidation in emulsions.

This study aimed to investigate the interaction, structure, antioxidant, and emulsification properties of quinoa protein hydrolysate (QPH) complexes formed with (-)-epigallocatechin gallate (EGCG) at pH 3.0 and 7.0. Additionally, the effect of pH conditions and EGCG complexation on protein hydrolysate-lipid co-oxidation in QPH emulsions was explored. The results indicated that QPH primarily interacted with EGCG through hydrophobic interactions and hydrogen bonds. This interaction led to alterations in the secondary structure of QPH, as well as a decrease in surface hydrophobicity and free SH content. Notably, the binding affinity between QPH and EGCG was observed to be higher at pH 7.0 compared to pH 3.0. Consequently, QPH-EGCG complexes exhibited more significant enhancement in antioxidant and emulsification properties at pH 7.0 than pH 3.0. The pH level also influenced the droplet size, ζ-potential, and interfacial composition of emulsions formed by QPH and QPH-EGCG complexes. Compared to QPH stabilized emulsions, QPH-EGCG stabilized emulsions were more capable of mitigating destabilization during storage and displayed fewer lipid oxidation products, carbonyl generation, and sulfhydryl groups and fluorescence loss, which implied better oxidative stability of the emulsions. Furthermore, the QPH-EGCG complexes formed at pH 7.0 exhibited better inhibition of protein hydrolysate-lipid co-oxidation. Overall, these findings provide valuable insights into the potential application of QPH and its complexes with EGCG in food processing systems.

Six new phenylpropanoids from Kaempferia galanga L. and their anti-inflammatory activity.

Kaempferia galanga L. is an aromatic medicinal plant belonging to the Zingiberaceae family. Its rhizome has been widely used as traditional Chinese medicine and a flavor spice for a long time. In this study, six previously undescribed phenylpropanoids, including four [2+2]-cycloaddition-derived cyclobutane natural products (1-4), and two phenylpropanoids (5-6) were isolated from the rhizomes of K. galanga L. Their structures were elucidated by spectroscopic methods, single-crystal X-ray diffraction, NMR calculation, and ECD spectra calculation. These cyclobutane derivatives were isolated from K. galanga for the first time. Furthermore, compounds 1-6 were evaluated for the potential inhibitory activities on NO production and NF-κB nuclear translocation in LPS-triggered RAW 264.7 macrophages. The results showed that the isolated compounds have a moderate anti-inflammatory activity measured on their potency to inhibit NO production and the expression of iNOS and COX-2. Additionally, compound 2 effectively suppressed NF-κB nuclear translocation at a concentration of 40 µM.

Endoscopic treatment of bleeding gastric ulcer causing gastric wall necrosis: A case report.

BACKGROUND: Gastric wall necrosis is a rare complication of endoscopic treatment for bleeding gastric ulcer, which may exacerbate the patient's condition once it occurs and may even require surgical intervention for treatment. CASE SUMMARY: A 59-year-old man was admitted to our department with melena. Endoscopy revealed a giant ulcer in the gastric antrum with a visible vessel in its center, which was treated with sclerosants and tissue glue injection and resulted in necrosis of the gastric wall. CONCLUSION: Injection of sclerosants and tissue glue may lead to gastric wall necrosis, which is a serious complication. Therefore, before administering this treatment to patients, we should consider other more effective methods of hemostasis to avoid gastric wall necrosis.

Structure-regulated enhanced Raman scattering on a semiconductor to study temperature-influenced enantioselective identification.

Surface-enhanced Raman scattering (SERS) spectroscopy is an effective technique that can reveal molecular structure and molecular interaction details. Semiconductor-based SERS platforms exhibit multifaceted tunability and unique selectivity to target molecules as well as high spectral reproducibility. However, the detection sensitivity of semiconductors is impeded by inferior SERS enhancement. Herein, a surface and interference co-enhanced Raman scattering (SICERS) platform based on corrugated TiO2 nanotube arrays (c-TiO2 NTs) was developed, and the coupling of structural regulation and photo-induced charge transfer (PICT) effectively optimized the SERS performance of the semiconductor substrate. Due to the regularly oscillating optical properties of the c-TiO2 NTs, well-defined interference patterns were generated and the local electric field was significantly increased, which greatly promoted both the electromagnetic mechanism and PICT processes. The c-TiO2 NTs were subsequently applied as a highly sensitive SICERS substrate to investigate the mechanism of temperature influence on enantioselective identification. This identification process is related to the existence of temperature-sensitive hydrogen bonds and π-π interaction. This work demonstrates a simply prepared, low-cost, and sensitive SERS substrate that enables better investigation into molecular identification.

Gastrointestinal microbiota and metabolites possibly contribute to distinct pathogenicity of SARS-CoV-2 proto or its variants in rhesus monkeys.

Gastrointestinal (GI) infection is evidenced with involvement in COVID-19 pathogenesis caused by SARS-CoV-2. However, the correlation between GI microbiota and the distinct pathogenicity of SARS-CoV-2 Proto and its emerging variants remains unclear. In this study, we aimed to determine if GI microbiota impacted COVID-19 pathogenesis and if the effect varied between SARS-CoV-2 Proto and its variants. We performed an integrative analysis of histopathology, microbiomics, and transcriptomics on the GI tract fragments from rhesus monkeys infected with SARS-CoV-2 proto or its variants. Based on the degree of pathological damage and microbiota profile in the GI tract, five of SARS-CoV-2 strains were classified into two distinct clusters, namely, the clusters of Alpha, Beta and Delta (ABD), and Proto and Omicron (PO). Notably, the abundance of potentially pathogenic microorganisms increased in ABD but not in the PO-infected rhesus monkeys. Specifically, the high abundance of UCG-002, UCG-005, and Treponema in ABD virus-infected animals positively correlated with interleukin, integrins, and antiviral genes. Overall, this study revealed that infection-induced alteration of GI microbiota and metabolites could increase the systemic burdens of inflammation or pathological injury in infected animals, especially in those infected with ABD viruses. Distinct GI microbiota and metabolite profiles may be responsible for the differential pathological phenotypes of PO and ABD virus-infected animals. These findings improve our understanding the roles of the GI microbiota in SARS-CoV-2 infection and provide important information for the precise prevention, control, and treatment of COVID-19.

Relationship between plasma risperidone concentrations and clinical features in chronic schizophrenic patients in China.

BACKGROUND: Prior studies have noted great variability in the plasma levels of risperidone (RIS). Plasma concentrations of RIS and its active moiety are highly variable and depend on absorption, metabolism, and other predictors of metabolic dysregulation; however, these factors are poorly understood and the association between metabolic change and change in psychopathology is uncertain. AIM: To ascertain the characteristics of chronic schizophrenic patients treated with RIS, and to assess their relationship with plasma RIS levels. METHODS: This was a descriptive cross-sectional study of 50 patients with a diagnosis of schizophrenic psychosis treated with RIS in a psychiatric service. The plasma concentrations of RIS and its metabolite 9-hydroxyrisperidone were determined by high performance liquid chromatography. The patients' demographic and clinical characteristics, and psychopathologies were assessed, and the associations between clinical variables and plasma levels of RIS were explored. RESULTS: Male patients received higher doses of RIS than female ones, but plasma concentrations of RIS and risperidone + 9-hydroxyrisperidone (active moiety) were higher in female patients. Age and the mean scores of the general psychopathology subscale of the Positive and Negative Syndrome Scale (PANSS) were significantly positively correlated with plasma concentrations of risperidone + 9-hydroxyrisperidone adjusted for weight and dose in all 50 subjects. In male subjects, we found a statistically significant positive correlation between the concentrations of risperidone + 9-hydroxyrisperidone in plasma/(dose × kg) and age, mean PANSS negative subscale scores, mean PANSS general psychopathology subscale scores, and mean PANSS total scores. CONCLUSION: Long-term use of RIS should be closely monitored in older patients and females to minimize the risk of high concentrations which could induce side effects.

Ruthenium-Based Binary Alloy with Oxide Nanosheath for Highly Efficient and Stable Oxygen Evolution Reaction in Acidic Media.

Traditional noble metal oxide, such as RuO2, is considered a benchmark catalyst for acidic oxygen evolution reaction (OER). However, its practical application is limited due to sluggish activity and severe electrochemical corrosion. In this study, Ru-Fe nanoparticles loading on carbon felt (RuFe@CF) is synthesized via an ultrafast Joule heating method as an active and durable OER catalyst in acidic conditions. Remarkably low overpotentials of 188 and 269 mV are achieved at 10 and 100 mA cm-2, respectively, with a robust stability up to 620 h at 10 mA cm-2. When used as an anode in a proton exchange membrane water electrolyzer, the catalyst shows more than 250 h of stability at a water-splitting current of 200 mA cm-2. Experimental characterizations reveal the presence of a Ru-based oxide nanosheath on the surface of the catalyst during OER tests, suggesting a surface reconstruction process that enhances the intrinsic activity and inhibits continuous metal dissolution. Moreover, density functional theory calculations demonstrate that the introduction of Fe into the RuFe@CF catalyst reduces the energy barrier and boosts its activities. This work offers an effective and universal strategy for the development of highly efficient and stable catalysts for acidic water splitting.

Efficient Intersystem Crossing in Extended Helical Perylene Diimide Dimers with Chalcogen-Annulation.

The properties and formation mechanisms of the triplet state have been widely investigated since they are crucial intermediates in photo functional devices. Specifically, helical PDI dimers, horizontal expanded π-conjugated derivatives of PDI, have shown outstanding performance as electron acceptors in enhancing the performance of photovoltaics. Therefore, the exploration of triplet generation in helical PDI dimers plays a crucial role in understanding the mechanisms and excavating their further application. We make use of Se-annulation to induce intersystem crossing (ISC) in helical PDI dimers and further explore the triplet evolution process systematically as the number of Se atoms increases by transient absorption spectroscopy and the hole-electron analysis method. It shows that the twisted molecular conformation has paved the way for potential ISC in a parent molecule PDI2. The incorporation of Se atoms can result in evident promotion in the efficiency of ISC (ϕTPDI2-2Se = 96.9%) compared to the parent molecule PDI2 (ϕTPDI2 = 26.5%), indicating that chalcogen-annulation is also an efficient strategy in a π-extended system. Our results provide useful insights for understanding the triplet evolution process, which can help broaden the application of the π-extended PDI system into high-performance photovoltaics.

Isoflavones isolated from the fruits of Ficus altissima and their anti-proliferative activities.

Ficus altissima, also known as lofty fig, is a monoecious plant from the Moraceae family commonly found in southern China. In this study, we isolated and identified one new isoflavone (1), three new hydroxycoumaronochromones (2a, 2b and 3a) and 12 known compounds from the fruits of F. altissima. Their chemical structures were determined using spectroscopic analysis methods. We also tested all the isolated compounds for their anti-proliferative activities against eight human tumour cell lines (A-549, AGS, K562, K562/ADR, HepG2, HeLa, SPC-A-1 and CNE2) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Our experiments showed that compound 6 exhibited obvious anti-proliferative activity against the K562 cell line with an IC50 value of 1.55 µM. Additionally, compounds 8 and 9 showed significant anti-proliferative activities against the AGS and K562 cell lines, respectively. Moreover, compound 6 induced apoptosis in K562 cells through the caspase family signalling pathway.

Symmetry-breaking charge separation in a null-excitonic 3-dimensional rigid nonconjugated trimer.

Photoinduced symmetry-breaking charge separation (SB-CS) has been extensively observed in various oligomers and aggregates, which holds great potential for robust artificial solar energy conversion systems. It attaches great importance to the precise manipulation of interchromophore electronic coupling in realizing efficient SB-CS. The emerging studies on SB-CS suggested that it could be realized in null-excitonic aggregates, and a long-lived SB-CS state was observed, which offers an advanced platform and has gathered immense attention in the SB-CS field. Here, we unveiled the null-exciton coupling induced ultrafast SB-CS in a rigid polycyclic aromatic hydrocarbon framework, triperyleno[3,3,3]propellane triimides (TPPTI), in which three chromophores were attached through a nonconjugated bridge. Through a combination of theoretical calculations and steady-state absorption results, we demonstrated that this nonconjugated TPPTI possesses negligible exciton coupling. Increased solvent polarity was found to significantly enhance state mixing between local excited and charge transfer states. Using transient absorption spectroscopy, ultrafast SB-CS was observed in highly polar dimethylformamide, facilitated by a selective hole-transfer coupling and a favorable charge separation free energy (ΔGCS). Additionally, the rate ratio between SB-CS and charge recombination was at least high to 1800 in dimethylformamide. This investigation provides profound insights into the role of null-exciton coupling in dominating ultrafast SB-CS in multichromophoric systems.

Antiproliferative piperidine alkaloids from the leaves of Alocasia macrorrhiza.

Seventeen piperidine alkaloids, including 15 previously undescribed 2-substituted-6-(9-phenylnonyl)-piperidine-3,4-diol alkaloids and a previously undescribed 2-substituted-6-(9-phenylnonyl)-piperidine-3-ol alkaloid, were isolated from the leaves of Alocasia macrorrhiza (L.) Schott. Their planar structures and configurations were elucidated based on HR-ESI-MS, 1D and 2D NMR, Snatzke's method, modified Mosher method, single-crystal X-ray crystallography, as well as quantum chemical calculation. It was found that ΔδH5b-H5a can be used to elucidate the relative configuration of 2,3,4,6-tetrasubstituted piperidine, by analyzing the NMR data of 2-substituted-6-(9-phenylnonyl)-piperidine-3,4-diol. Antiproliferative activity was evaluated for all of the alkaloids, and compounds 6-8 showed considerable inhibitory activity against K562 cell line, with the IC50 values of 17.24 ± 1.62, 19.31 ± 0.9 and 18.77 ± 1.09µM, respectively. Furthermore, compounds 6 and 7 exerted an antiproliferative effect by inducing apoptosis.

Ultrafine grinding improves the nutritional, physicochemical, and antioxidant activities of two varieties of whole-grain highland barley.

Effects of ultrafine grinding on the nutritional profile, physicochemical properties, and antioxidant activities of whole-grain highland barley (HB) including white highland barley (WHB) and black highland barley (BHB) were studied. Whole-grain HB was regularly ground and sieved through 80 mesh get 80 M powder, and HB was ultrafine grounded and sieved through 80 mesh, 150 mesh, and 200 mesh get 80UMM, 150UMM, and 200UMM samples. Particle size of WHB and BHB reduced significantly after ultrafine grinding. As the particle size decreased, moisture content of WHB and BHB decreased significantly, whereas fat content increased significantly. Redistribution of fiber components in WHB and BHB from insoluble to soluble fractions was also observed. Wherein, content of soluble pentosan of WHB and BHB increased significantly from 0.56% and 0.78% (80 M) to 0.91% and 1.14% (200UMM), respectively. Damaged starch of WHB and BHB increased significantly from 8.16% and 8.21% (80 M) to 10.29% and 10.07% (200UMM), respectively. Content of phenolic acid and flavonoid of WHB and BHB and associated antioxidant capacity were increased after ultrafine grinding. Color of L* value increased significantly, a* and b* values decreased significantly, indicating the whiteness of WHB and BHB was increased after ultrafine grinding. Pasting temperature of WHB and BHB decreased, whereas peak viscosity increased. X-ray diffraction patterns of HB showed typical A- and V-style polymorphs and the relative crystallinity of HB decreased as the particle size decreased. Taken together, ultrafine grinding has shown great potential in improving the nutritional, physiochemical, and antioxidant properties of whole-grain HB. Our research findings could help better understand the ultrafine grinded whole grain HB in food industry.

Relevance and antimicrobial resistance profile of Klebsiella pneumoniae in neonatal sepsis.

BACKGROUND: Newborns are particularly susceptible to infection in hospitals, with neonatal sepsis being the most common infection symptom and the third leading cause of neonatal death. Klebsiella pneumoniae is a gram-negative bacterium of Enterobacteriaceae, which is a common pathogen of neonatal septicemia. In this study, we will analyze and evaluate the current status, clinical characteristics, and drug resistance of Klebsiella pneumoniaesepsis infection in Neonatal Intensive Care Unit (NICU), with the aim of providing effective basis for timely and accurate clinical diagnosis and treatment in clinical practice. METHODS: Statistical analysis was performed on 75 cases of Enterobacteriaceae septicemia in infants admitted to NICU in a special obstetrics and gynecology hospital in Shanghai from January 2020 to June 2022. Based on bacterial identification, isolates were divided into the Klebsiella pneumoniae (KP) group (n = 49) and the non-KP Enterobacteriaceae group (n = 26). The infection, clinical characteristics, and bacterial resistance of the two groups of infected patients were compared. RESULTS: Comparing the clinical characteristics of the two groups, the results showed that most of the subjects in the KP and non-KP groups were premature infants, accounting for 100% and 92.3% of subjects, respectively; late onset was the main disease in both groups, accounting for 93.9% and 80.8% of subjects, respectively. All patients received Peripherally Inserted Central Catheter(PICC). The levels of pro calcitonin and CRP (C-reactive protein) were significantly higher in the KP group compared with those in the non-KP group (p < .05). At the same time, the incidence of thrombocytopenia in the KP group was significantly higher than that in the non-KP group (p < .05). The proportion of antimicrobial drug exposure in the KP group is higher than that in the non-KP group. The drug resistance of the KP group to ceftazidime, ceftriaxone, cefepime, ampicillin/sulbactam, aztreonam, ciprofloxacin and compound sulfamethoxazole was significantly higher than that of the non-KP group, whereas the drug resistance rate to cefotetan, gentamycin and to bramycin was significantly lower than that of the non-KP group, Statistically significant differences (p < .05). 38 cases of Klebsiella pneumoniae producing ESBLs were tested for related resistance genes. The results showed that the main resistance types were SHV and TEM, with detection rates of 60.6% and 28.9%. CONCLUSIONS: This study shows that neonatal sepsis caused by Klebsiella pneumoniae infection has a high incidence and drug resistance in premature and low birth weight infants, and has become a serious public health problem; Clinicians should pay attention to differential diagnosis, Reasonable selection of antibiotics to reduce the generation of drug-resistant bacteria.

Appending Coronene Diimide with Carbon Nanohoops Allows for Rapid Intersystem Crossing in Neat Film.

The development of innovative triplet materials plays a significant role in various applications. Although effective tuning of triplet formation by intersystem crossing (ISC) has been well established in solution, the modulation of ISC processes in the solid state remains a challenge due to the presence of other exciton decay channels through intermolecular interactions. The cyclic structure of cycloparaphenylenes (CPPs) offers a unique platform to tune the intermolecular packing, which leads to controllable exciton dynamics in the solid state. Herein, by integrating an electron deficient coronene diimide (CDI) unit into the CPP framework, a donor-acceptor type of conjugated macrocycle (CDI-CPP) featuring intramolecular charge-transfer (CT) interaction was designed and synthesized. Effective intermolecular CT interaction resulting from a slipped herringbone packing was confirmed by X-ray crystallography. Transient spectroscopy studies showed that CDI-CPP undergoes ISC in both solution and the film state, with triplet generation time constants of 4.5 ns and 238 ps, respectively. The rapid triplet formation through ISC in the film state can be ascribed to the cooperation between intra- and intermolecular charge-transfer interactions. Our results highlight that intermolecular CT interaction has a pronounced effect on the ISC process in the solid state, and shed light on the use of the characteristic structure of CPPs to manipulate intermolecular CT interactions.

Complex causal association between genetically predicted 731 immunocyte phenotype and osteonecrosis: A bidirectional Two-sample mendelian randomization analysis.

PURPOSE: Previous studies have explored the role of immune cells on osteonecrosis. This Mendelian randomization (MR) study further assessed 731 immunocyte phenotypes on osteonecrosis whether a causal relationship exists and provides some evidence of causality. METHODS: The 731 immunocyte phenotypes and osteonecrosis data used in this study were obtained from their respective genome-wide association studies (GWAS). We used inverse variable weighting (IVW) as the primary analysis method. In addition, we simultaneously employed multiple analytical methods, including MR-Egger, weighted mode, simple mode, and weighted median, to strengthen the final results. Finally, sensitivity analyses were conducted to verify the stability and feasibility of the data. RESULTS: The results of the IVW method of MR analysis showed that 8 immunocyte phenotypes were positively associated with osteonecrosis (P<0.05, OR > 1); 18 immunocyte phenotypes were negatively associated with osteonecrosis (P<0.05, OR<1), none of which were heterogeneous or horizontally pleiotropic (P > 0.05) or reverse causality. In addition to this, in reverse MR, osteonecrosis was positively associated with 10 additional immunocyte phenotypes (P<0.05, OR > 1) and negatively associated with 14 immunocyte phenotypes (P<0.05, OR<1). And none of them had heterogeneity and horizontal pleiotropy (P > 0.05) or reverse causality. CONCLUSIONS: We demonstrated a complex causal relationship between multiple immune phenotypes and osteonecrosis through a comprehensive two-way two-sample MR analysis, highlighting the complex pattern of interactions between the immune system and osteonecrosis.

Advances in the differentiation of pluripotent stem cells into vascular cells.

Blood vessels constitute a closed pipe system distributed throughout the body, transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys. Changes in blood vessels are related to many disorders like stroke, myocardial infarction, aneurysm, and diabetes, which are important causes of death worldwide. Translational research for new approaches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems. Although mice or rats have been widely used, applying data from animal studies to human-specific vascular physiology and pathology is difficult. The rise of induced pluripotent stem cells (iPSCs) provides a reliable in vitro resource for disease modeling, regenerative medicine, and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells. This review summarizes the latest progress from the establishment of iPSCs, the strategies for differentiating iPSCs into vascular cells, and the in vivo transplantation of these vascular derivatives. It also introduces the application of these technologies in disease modeling, drug screening, and regenerative medicine. Additionally, the application of high-tech tools, such as omics analysis and high-throughput sequencing, in this field is reviewed.