A Planar-Structured Dinuclear Cobalt(II) Complex with Indirect Synergy for Photocatalytic CO2-to-CO Conversion.

Dinuclear metal synergistic catalysis (DMSC) has been proved an effective approach to enhance catalytic efficiency in photocatalytic CO2 reduction reaction, while it remains challenge to design dinuclear metal complexes that can show DMSC effect. The main reason is that the influence of the microenvironment around dinuclear metal centres on catalytic activity has not been well recognized and revealed. Herein, we report a dinuclear cobalt complex featuring a planar structure, which displays outstanding catalytic efficiency for photochemical CO2-to-CO conversion. The turnover number (TON) and turnover frequency (TOF) values reach as high as 14457 and 0.40 s-1 respectively, 8.6 times higher than those of the corresponding mononuclear cobalt complex. Control experiments and theoretical calculations revealed that the enhanced catalytic efficiency of the dinuclear cobalt complex is due to the indirect DMSC effect between two CoII ions, energetically feasible one step two-electron transfer process by Co2 I,I intermediate to afford Co2 II,II(CO2 2-) intermediate and fast mass transfer closely related with the planar structure.

Modulating the Microenvironments of Robust Metal Hydrogen-Bonded Organic Frameworks for Boosting Photocatalytic Hydrogen Evolution.

Hydrogen-bonded organic frameworks (HOFs) are outstanding candidates for photocatalytic hydrogen evolution. However, most of reported HOFs suffer from poor stability and photocatalytic activity in the absence of Pt cocatalyst. Herein, a series of metal HOFs (Co2-HOF-X, X=COOMe, Br, tBu and OMe) have been rationally constructed based on dinuclear cobalt complexes, which exhibit exceptional stability in the presence of strong acid (12 M HCl) and strong base (5 M NaOH) for at least 10 days. More impressively, by varying the -X groups of the dinuclear cobalt complexes, the microenvironment of Co2-HOF-X can be modulated, giving rise to obviously different photocatalytic H2 production rates, following the -X group sequence of -COOMe>-Br>-tBu>-OMe. The optimized Co2-HOF-COOMe shows H2 generation rate up to 12.8 mmol g-1 h-1 in the absence of any additional noble-metal photosensitizers and cocatalysts, which is superior to most reported Pt-assisted photocatalytic systems. Experiments and theoretical calculations reveal that the -X groups grafted on Co2-HOF-X possess different electron-withdrawing ability, thus regulating the electronic structures of Co catalytic centres and proton activation barrier for H2 production, and leading to the distinctly different photocatalytic activity.

Development of a predictive nomogram for intermediate-risk differentiated thyroid cancer patients after fixed 3.7GBq (100mCi) radioiodine remnant ablation.

Objectives: The objective of this study was to develop a predictive nomogram for intermediate-risk differentiated thyroid cancer (DTC) patients after fixed 3.7GBq (100mCi) radioiodine remnant ablation (RRA). Methods: Data from 265 patients who underwent total thyroidectomy with central lymph node dissection (CND) and received RRA treatment at a single institution between January 2018 and March 2023 were analyzed. Patients with certain exclusion criteria were excluded. Univariate and multivariate logistic regression analyses were performed to identify risk factors for a non-excellent response (non-ER) to RRA. A nomogram was developed based on the risk factors, and its performance was validated using the Bootstrap method with 1,000 resamplings. A web-based dynamic calculator was developed for convenient application of the nomogram. Results: The study included 265 patients with intermediate-risk DTC. Significant differences were found between the ER group and the non-ER group in terms of CLNM>5, Hashimoto's thyroiditis, sTg level, TgAb level (P < 0.05). CLNM>5 and sTg level were identified as independent risk factors for non-ER in multivariate analysis. The nomogram showed high accuracy, with an area under the curve (AUC) of 0.833 (95% CI = 0.770-0.895). The nomogram's predicted probabilities aligned closely with actual clinical outcomes. Conclusions: This study developed a predictive nomogram for intermediate-risk DTC patients after fixed 3.7GBq (100mCi) RRA. The nomogram incorporates CLNM>5 and sTg levels as risk factors for a non-ER response to RRA. The nomogram and web-based calculator can assist in treatment decision-making and improve the precision of prognosis information. Further research and validation are needed.

Chinese patent medicines for coronary microvascular disease: clinical evidence and potential mechanisms.

Coronary microvascular disease (CMVD) is a high risk factor for many cardiovascular events. Due to the limited understanding of its pathophysiological mechanism, modern medicine still lacks therapeutic drugs for CMVD. Existing clinical studies have shown that traditional Chinese medicine (TCM) can effectively improve the clinical symptoms and quality of life of CMVD patients. As an indispensable part of TCM, Chinese patent medicines (CPMs) are widely used in clinical practice. In the face of numerous oral CPMs for treatment of CMVD, how to choose a reasonable medication regimen is one of the important issues in clinic. Based on this, this paper reviewed the clinical efficacy and recommended level of 12 CPMs in the treatment of CMVD, which are recommended by expert consensus on diagnosis and treatment of coronary microvascular disease with integrated Chinese and Western medicine (WM). In addition, this study also systematically summarized the possible mechanisms of CPMs in the treatment of CMVD by protecting coronary microvascular endothelial cells, improving vascular endothelial function, inhibiting inflammation, reducing oxidative stress, promoting angiogenesis, and improving hemorheology, aiming to provide meaningful information for its clinical application.

Targeting intestinal microecology: potential intervention strategies of traditional Chinese medicine for managing hypertension.

Hypertension has become one of the major public health problems in the world. At present, the pathogenesis of hypertension has still not been completely elucidated. In recent years, an increasing evidence shows that intestinal microecology is closely related to hypertension, which provides a new thinking for the prevention and treatment of hypertension. Traditional Chinese medicine (TCM) has unique advantages in the treatment of hypertension. Taking intestinal microecology as the target, it is possible to interpreting the scientific connotation of TCM prevention and treatment of hypertension by updating the treatment concept of hypertension, so as to improve the therapeutic effect. In our study, the clinical evidence for TCM treatment of hypertension was systematicly summarized. And the relationship among TCM, intestinal microecology and hypertension was analyzed. In addition, the methods by which TCM regulates intestinal microecology to prevent and treat hypertension were presented, to provide new research ideas for prevention and treatment of hypertension.

Coronary microvascular dysfunction and cardiovascular disease: Pathogenesis, associations and treatment strategies.

Coronary microvascular dysfunction (CMD) is a high-risk factor for a variety of cardiovascular events. Due to its complex aetiology and concealability, knowledge of the pathophysiological mechanism of CMD is still limited at present, which greatly restricts its clinical diagnosis and treatment. Studies have shown that CMD is closely related to a variety of cardiovascular diseases, can aggravate the occurrence and development of cardiovascular diseases, and is closely related to a poor prognosis in patients with cardiovascular diseases. Improving coronary microvascular remodelling and increasing myocardial perfusion might be promising strategies for the treatment of cardiovascular diseases. In this paper, the pathogenesis and functional assessment of CMD are reviewed first, along with the relationship of CMD with cardiovascular diseases. Then, the latest strategies for the treatment of CMD and cardiovascular diseases are summarized. Finally, urgent scientific problems in CMD and cardiovascular diseases are highlighted and future research directions are proposed to provide prospective insights for the prevention and treatment of CMD and cardiovascular diseases in the future.

Gut microbiota and hypertension: association, mechanisms and treatment.

OBJECTIVES: Hypertension is one of the most important risk factors for cardio-cerebral vascular diseases, which brings a heavy economic burden to society and becomes a major public health problem. At present, the pathogenesis of hypertension is unclear. Increasing evidence has proven that the pathogenesis of hypertension is closely related to the dysbiosis of gut microbiota. We briefly reviewed relevant literature on gut microbiota and hypertension to summarize the relationship between gut microbiota and hypertension, linked the antihypertension effects of drugs with their modulation on gut microbiota, and discussed the potential mechanisms of various gut microbes and their active metabolites to alleviate hypertension, thus providing new research ideas for the development of antihypertension drugs. METHODS: The relevant literature was collected systematically from scientific database, including Elsevier, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Baidu Scholar, as well as other literature sources, such as classic books of herbal medicine. RESULTS: Hypertension can lead to gut microbiota imbalance and gut barrier dysfunction, including increased harmful bacteria and hydrogen sulfide and lipopolysaccharide, decreased beneficial bacteria and short-chain fatty acids, decreased intestinal tight junction proteins and increased intestinal permeability. Gut microbiota imbalance is closely related to the occurrence and development of hypertension. At present, the main methods to regulate the gut microbiota include fecal microbiota transplantation, supplementation of probiotics, antibiotics, diet and exercise, antihypertensive drugs, and natural medicines. CONCLUSIONS: Gut microbiota is closely related to hypertension. Investigating the correlation between gut microbiota and hypertension may help to reveal the pathogenesis of hypertension from the perspective of gut microbiota, which is of great significance for the prevention and treatment of hypertension.

Inheritance of perturbed methylation and metabolism caused by uterine malnutrition via oocytes.

BACKGROUND: Undernourishment in utero has deleterious effects on the metabolism of offspring, but the mechanism of the transgenerational transmission of metabolic disorders is not well known. In the present study, we found that undernourishment in utero resulted in metabolic disorders of female F1 and F2 in mouse model. RESULTS: Undernutrition in utero induced metabolic disorders of F1 females, which was transmitted to F2 females. The global methylation in oocytes of F1 exposed to undernutrition in utero was decreased compared with the control. KEGG analysis showed that genes with differential methylation regions (DMRs) in promoters were significantly enriched in metabolic pathways. The altered methylation of some DMRs in F1 oocytes located at the promoters of metabolic-related genes were partially observed in F2 tissues, and the expressions of these genes were also changed. Meanwhile, the abnormal DNA methylation of the validated DMRs in F1 oocytes was also observed in F2 oocytes. CONCLUSIONS: These results indicate that DNA methylation may mediate the transgenerational inheritance of metabolic disorders induced by undernourishment in utero via female germline.

Epigallocatechin gallate improves the quality of diabetic oocytes.

BACKGROUND: Maternal diabetes compromises the quality and developmental potential of oocytes. Therefore, it is important to study how to ameliorate the adverse effects of diabetes on oocyte quality. Epigallocatechin gallate (EGCG) has a variety of physiological activities, including anti-inflammatory, antioxidant, and anti-diabetes. In the present study, we evaluated the effect of EGCG on the maturation of diabetic oocytes in vitro. OBJECTIVE: Investigating the role of EGCG in restoring the adverse effects of diabetes on oocyte quality. METHODS: Diabetes mouse model was established by a single injection of streptozotocin (STZ). Oocytes were collected and matured in vitro with/without EGCG in M16 medium. RESULTS: Compared with control, diabetic oocytes have a higher frequency of spindle defects and chromosome misalignment, but EGCG effectively reduces the incidence of oocytes with abnormal spindle assembly and chromosome mismatches. Moreover, the abnormal mitochondrial membrane potential (MMP) of diabetic oocytes is significantly alleviated by EGCG, and the reduced expression of genes regulating mitochondrial fusion (Mfn1 and Mfn2) and fission (Drp1) in diabetic oocytes is significantly increased while EGCG is added. EGCG also decreases the higher level of reactive oxygen species (ROS) in diabetic oocytes that may be regulated by the increased expression of superoxide dismutase 1 (Sod1) and superoxide dismutase 2 (Sod2). EGCG can also reduce the DNA damage of diabetic oocytes. CONCLUSIONS: Our results suggest that EGCG, at least partially, improve the quality of diabetic oocytes.

Protocatechuic Acid Delays Postovulatory Oocyte Ageing in Mouse.

SCOPE: Tea is a popular beverage worldwide and has many health functions. Protocatechuic acid (PCA) is an important bioactive component of tea and has benefit to health. In some cases, oocytes after ovulation may miss the optimal fertilization time and enter a postovulatory ageing process. Therefore, to investigate the role of PCA in delaying oocyte ageing is aimed. METHODS AND RESULTS: Metaphase II (MII) oocytes aged in vitro are randomly divided into three groups: control, aged, and aged + PCA. PCA treatment (30 µM) reduces the fragmentation rate and the incidence of abnormal spindle morphology and chromosome misalignment of oocytes aged 24 h in vitro. The mitochondrial dysfunction of aged oocytes, such as decreased mitochondrial membrane potential and excessive accumulation of reactive oxygen (ROS), is also alleviated by PCA. PCA also delays apoptosis of aged oocytes, and improves the sperm binding capacity. Otherwise, aged oocytes treated with PCA have a higher fertilization rate and blastocyst rate compared with untreated aged oocytes in vitro. CONCLUSION: PCA is an important bioactive ingredient of tea that improves aged oocyte quality, suggesting that PCA is available to improve the quality of aged oocytes in vitro.

Epigallocatechin gallate improves meiosis maturation against Diazinon exposure in porcine oocytes.

Diazinon (DZN) is a refractory organophosphorus pesticide (OP) in the surrounding environment due to its overuse in agriculture. The antioxidant activity of Epigallocatechin gallate (EGCG) from green tea is at least 100 times greater than that of vitamin C. This study aimed to study the effects of DZN on the meiotic maturation of porcine oocytes, as well as the protective roles of EGCG. Firstly, the effects of DZN and EGCG on meiotic nuclear maturation of porcine oocytes were detected, and then embryonic development was investigated by chemical parthenogenetic activation. Next, the spindle assembly, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), DNA damage, and finally the early apoptosis of oocytes were examined by immunofluorescence staining. The results revealed that DZN exposure significantly reduced the quality of porcine oocytes, such as failure of nuclear and cytoplasmic maturation, evidenced by abnormal spindle assembly, disordered chromosome alignment, low MMP, observably increased ROS, severe DNA damage, and early apoptosis. Appropriate EGCG could significantly reduce all these defects caused by DZN. In conclusion, EGCG can help prevent the harm that DZN exposure can do. These findings offer convincing support for enhancing the oocyte quality from EGCG through daily ordinary beverages.

[Clinical efficacy of oblique lumbar interbody fusion combined with unilateral pedicle screw fixation via Wiltse approach in the treatment of lumbar spinal stenosis].

OBJECTIVE: To evaluate the efficacy of oblique lumbar interbody fusion combined with unilateral pedicle screw fixation via Wiltse approach in the treatment of lumbar spinal stenosis. METHODS: From July 2017 to January 2019, 90 patients with lumbar spinal stenosis, including 38 males and 52 females, aged from 43 to 75 years old with an average of(59.9±8.8) years old, and were treated with oblique lumbar interbody fusion(OLIF) combined with Wiltse unilateral pedicle screw fixation. Surgical decompression and fixation was performed in 50 cases of single segment, 32 cases of double segments and 8 cases of three segments. The distribution of responsible segments included 8 cases of L2-L3, 12 cases of L3-L4 and 30 cases of L4-L5 on single segment, 10 cases of L2-L4 and 22 cases of L3-L5 on double segments, and 8 cases of L2-L5 on three segments. The operation time, blood loss and occurrence of complications were recorded, Visual analogue scale(VAS), Oswestry Disability Index(ODI) and SF-36 scale were used to evaluate clinical efficacy. Lumbar X-ray and MRI were taken at three days after operation, interverterbral space height, intervertebral foraminal height, interverterbral foraminal area, and spinal canal area were measured, and interbody fusion was evaluated according to CT at half a year after operation. RESULTS: All patients were followed up from 12 to 33 months, with an average of (20.2±6.6) months. Mean operation time was (103.3±35.9) min, and mean intraoperative blood loss was (70.4±17.8) ml. VAS of low back pain leg pain, and ODI decreased from 6.2±1.1, 6.1±0.9 and (59.9±4.2)% to 2.7±0.5, 2.5±0.5 and (31.3±8.8)%. SF-36 scale significantly increased from (37.2±3.1) to (54.9±6.1) at the six months postoperation(P<0.05). The intervertebral space height, intervertebral foraminal height, intervertebral foraminal area, and spinal canal area were significantly improved at 3 days after operation(P<0.05). Six months after operation, CT scan showed well fusion in 87 cases, but 3 cases with poor fusion, including 1 case of single segment, 2 cases of multi-segments. The total fusion rate was 96.7% (87/90), the single segment fusion rate was 98.0% (49/50), and the multi-segments fusion rate was 95.0%(38/40). The overall incidence of complications was 17.8%(16/90), including transient iliopsoas muscle weakness in 5 cases (5.6%), endplate fracture in 2 cases (2.2%), peritoneal injury in 1 case (1.1%), postoperative hematoma in 1 case (1.1%), adjacent segment disease in 1 case(1.1%), and fusion cage subsidence in 6 cases (6.7%). Three patients was followed up for recurrent nerve root pain and the symptoms were relieved after revision operation. All complications were relieved or disappeared in varying degrees during the follow-up period, and there were no complications such as cage displacement and screw fracture. CONCLUSION: OLIF combined with unilateral pedicle screw fixation via Wiltse approach is effective in treating lumbar spinal stenosis with minimally invasive advantages such as less trauma and less complications. Under the premise of strictly grasping the indications, this method could also achieve satisfactory clinical results in multi-segments oprations.

Traditional chinese medicine in coronary microvascular disease.

Coronary microvascular disease (CMVD) is common in patients with cardiovascular risk factors and is associated with an increased risk of adverse cardiovascular events. Although the study of CMVD in modern medicine is ongoing, there is still no effective treatment for it. Traditional Chinese medicine (TCM) has some clinical advantages based on syndrome differentiation and individualized treatment. In this review, we review the clinical significance, pathogenesis, and current treatments of CMVD and systematically summarize the clinical efficacy and potential action mechanisms of TCM for CMVD. In addition, the scientific problems that need to be solved urgently and the research strategy of TCM for CMVD are described. CMVD has great clinical significance, but there are still many gaps in the related research. This review aims to attract the attention of clinicians to CMVD and promote research on CMVD in TCM.

Paraneoplastic neurological syndrome with positive anti-Hu and anti-Yo antibodies: A case report.

BACKGROUND: Paraneoplastic neurological syndrome (PNS) is a rare complication in patients with cancer. PNS can affect the central, peripheral, autonomic nervous system, neuromuscular junction, or muscles and cause various neurological symptoms. Anti-Yo antibody-positive neurological paraneoplasms and anti-Hu antibody-positive neurological paraneoplasms are common, but coexistence of both types has not been described in the literature. CASE SUMMARY: Here we present a rare case of paraneoplastic neuropathy occurring in both breast and lung cancers. A 55-year-old woman was admitted to our hospital with unsteadiness while walking. The patient had a history of breast cancer two years previously. Chest computed tomography revealed a 4.6 cm × 3.6 cm mass in the right lung, which was diagnosed as small-cell lung cancer (SCLC). Blood test was positive for anti-Yo antibodies, and the cerebrospinal fluid was positive for both anti-Yo and anti-Hu antibodies, and the neurological symptoms were considered to be related to the paraneoplasm. The patient was treated with a course of intravenous immunoglobulin, without noticeable improvement. After being discharged from hospital, the patient underwent regular chemotherapy for SCLC and periodic reviews. The patient's neurological symptoms continued to deteriorate at the follow-up visit in April 2021. CONCLUSION: This case suggests the possibility of two types of tumors appearing simultaneously with two paraneoplastic antibodies. The clinical appearance of two or more paraneoplastic tumors requires additional attention.

Melatonin improves meiosis maturation against diazinon exposure in mouse oocytes.

AIMS: Organophosphorus pesticide diazinon (DZN) has adverse effects on animals and humans by direct contact or the spread of food chain. The antioxidant melatonin has protective effects on female reproduction. This study aimed to explore the effects of DZN on meiosis maturation in mouse cumulus oocyte complexes (COCs) and the effects of melatonin. MAIN METHODS: Different concentrations of DZN and melatonin were added during the in vitro maturation of COCs. Then we detected the extrusion rate of the first polar body, the number of sperms binding to oocyte, mitochondrial membrane potential, reactive oxygen species (ROS), early apoptosis. Subsequently, the expression of Juno, CX37, CX43 and ERK1/2 were detected by immunofluorescence staining and Western blotting. KEY FINDINGS: DZN exposure results in the failure of nuclear and cytoplasmic maturation of oocyte meiosis. Destruction of repositioning and function of mitochondria increases the levels of ROS and early apoptosis. The DZN-exposed oocytes express less Juno resulting to bind less sperms than normal. The loss of gap junctions and failure to activate ERK1/2 also contribute to the failure of cytoplasmic maturation. All these ultimately lead to the poor oocyte quality and low fertility. Appropriate melatonin can effectively restore all these defects. SIGNIFICANCE: Under DZN exposure, melatonin can significantly improve the quality of oocytes, and melatonin promotes oocyte maturation by protecting gap junction and restoring ERK1/2 pathway, which is a new breakthrough for improving female fertility.

Reduction of mtDNA heteroplasmy in mitochondrial replacement therapy by inducing forced mitophagy.

Mitochondrial replacement therapy (MRT) has been used to prevent maternal transmission of disease-causing mutations in mitochondrial DNA (mtDNA). However, because MRT requires nuclear transfer, it carries the risk of mtDNA carryover and hence of the reversion of mtDNA to pathogenic levels owing to selective replication and genetic drift. Here we show in HeLa cells, mouse embryos and human embryos that mtDNA heteroplasmy can be reduced by pre-labelling the mitochondrial outer membrane of a donor zygote via microinjection with an mRNA coding for a transmembrane peptide fused to an autophagy receptor, to induce the degradation of the labelled mitochondria via forced mitophagy. Forced mitophagy reduced mtDNA carryover in newly reconstructed embryos after MRT, and had negligible effects on the growth curve, reproduction, exercise capacity and other behavioural characteristics of the offspring mice. The induction of forced mitophagy to degrade undesired donor mtDNA may increase the clinical feasibility of MRT and could be extended to other nuclear transfer techniques.

Tea polyphenols alleviate the adverse effects of diabetes on oocyte quality.

Maternal diabetes mellitus reduces oocyte quality, such as abnormalities of spindle assembly and chromosome segregation, mitochondrial dysfunction, decrease of fertilization rate, increase of ROS, and so on. So, it is important to research how to restore the decreased oocyte quality induced by maternal diabetes mellitus. Polyphenols are the most abundant bioactive components of green tea. It is reported that tea polyphenols have many health functions, for instance anti-oxidation, anti-inflammation, anti-obesity, and anti-diabetes. Thus, we hypothesize that tea polyphenols may play a crucial role in alleviating adverse effects of diabetes on oocyte quality. In the present study, we researched the effects of tea polyphenols on diabetic oocyte maturation in vitro. Compared with the control, oocytes from diabetic mice displayed a lower maturation rate and a higher frequency of spindle defects and chromosome misalignment. However, tea polyphenols significantly increased the oocyte maturation rate, and reduced the incidence of abnormal spindle assembly and chromosome segregation. Tea polyphenols also obviously decreased the reactive oxygen species (ROS) levels in diabetic oocytes, and increased the expression of antioxidant genes (Sod1 and Sod2). Abnormal mitochondrial membrane potential was also alleviated in diabetic oocytes, and the expression of genes regulating mitochondrial fusion (Opa1, Mfn1 and Mfn2) and fission (Drp1) was significantly increased while tea polyphenols were added. Meanwhile, tea polyphenols reduced DNA damage in diabetic oocytes which may be mediated by the increased expression of Rad51, related to DNA damage repair. Our results suggest that tea polyphenols would, at least partially, restore the adverse effects of diabetes mellitus on oocyte quality.