His bundle pacing versus left bundle branch pacing on ventricular function in atrial fibrillation patients referred for pacing: a prospective crossover comparison.

BACKGROUND: His bundle pacing (HBP) and left bundle branch pacing (LBBP) both provide physiologic pacing which maintain left ventricular synchrony. They both improve heart failure (HF) symptoms in atrial fibrillation (AF) patients. We aimed to assess the intra-patient comparison of ventricular function and remodeling as well as leads parameters corresponding to two pacing modalities in AF patients referred for pacing in intermediate term. METHODS: Uncontrolled tachycardia AF patients with both leads implantation successfully were randomized to either modality. Echocardiographic measurements, New York Heart Association (NYHA) classification, quality-of-life assessments and leads parameters were obtained at baseline and at each 6-month follow up. Left ventricular function including the left ventricular endo-systolic volume (LVESV), left ventricular ejection fraction (LVEF) and right ventricular (RV) function quantified by tricuspid annular plane systolic excursion (TAPSE) were all assessed. RESULTS: Consecutively twenty-eight patients implanted with both HBP and LBBP leads successfully were enrolled (69.1 ± 8.1 years, 53.6% male, LVEF 59.2% ± 13.7%). The LVESV was improved by both pacing modalities in all patients (n = 23) and the LVEF was improved in patients with baseline LVEF at less than 50% (n = 6). The TAPSE was improved by HBP but not LBBP (n = 23). CONCLUSION: In this crossover comparison between HBP and LBBP, LBBP was found to have an equivalent effect on LV function and remodeling but better and more stable parameters in AF patients with uncontrolled ventricular rates referred for atrioventricular node (AVN) ablation. HBP could be preferred in patients with reduced TAPSE at baseline rather than LBBP.

Rise and metabolic roles of Vibrio during the fermentation of crab paste.

Microbial community may systematically promote the development of fermentation process of foods. Traditional fermentation is a spontaneous natural process that determines a unique nutritional characteristic of crab paste of Portunus trituberculatus, However, rare information is available regarding the development pattern and metabolic role of bacterial community during the fermentation of crab paste. Here, using a 16S rRNA gene amplicon sequencing technology, we investigated dynamics of bacterial community and its relationship with metabolites during the fermentation of crab paste. The results showed that bacterial community changed dynamically with the fermentation of crab paste which highlighted by consistently decreased α-diversity and overwhelming dominance of Vibrio at the later days of fermentation. Vibrio had a positive correlation with trimethylamine, hypoxanthine, formate, and alanine while a negative correlation with inosine and adenosine diphosphate. In contrast, most of other bacterial indicators had a reverse correlation with these metabolites. Moreover, Vibrio presented an improved function potential in the formation of the significantly increased metabolites. These findings demonstrate that the inexorable rise of Vibrio not only drives the indicator OTUs turnover in the bacterial community but also has incriminated the quality of crab paste from fresh to perished.

Analgesic efficacy of theta-burst stimulation for postoperative pain.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) may be a relevant method to assist postoperative pain. However, studies to date have only used conventional 10 Hz rTMS and targeted the DLPFC for postoperative pain. A more recent form of rTMS, termed intermittent Theta Burst Stimulation (iTBS), enables to increase cortical excitability in a short period of time. This preliminary double-blind, randomised, sham controlled study was designed to evaluate the efficacy of iTBS in postoperative care across two distinct stimulation targets. METHODS: A group of 45 patients post laparoscopic surgery were randomised to receive a single session of iTBS over either the dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1), or Sham stimulation (1:1:1 ratio). Outcome measurements were number of pump attempts, total anaesthetic volume used, and self-rated pain experience, assessed at 1 hour, 6 hours, 24 hours, and 48 hours post stimulation. All randomised patients were analysed (n = 15 in each group). RESULTS: Compared to Sham stimulation, DLPFC-iTBS reduced pump attempts at 6 (DLPFC = 0.73 ± 0.88, Sham = 2.36 ± 1.65, P = 0.031), 24 (DLPFC = 1.40 ± 1.24, Sham = 5.03 ± 3.87, P = 0.008), and 48 (DLPFC = 1.47 ± 1.41, Sham = 5.87 ± 4.34, P = 0.014) hours post-surgery, whereby M1 stimulation had no effect. No group effect was observed on total anaesthetics, which was mainly provided through the continuous administration of opioids at a set speed for each group. There was also no group or interaction effect on pain ratings. Pump attempts were positively associated with pain ratings in the DLPFC (r = 0.59, P = 0.02) and M1 (r = 0.56, P = 0.03) stimulation. CONCLUSIONS: Our findings show that iTBS to the DLPFC reduces pump attempts for additional anaesthetics following a laparoscopic surgery. However, reduced pump attempts by DLPFC stimulation did not translate into a significantly smaller volume of total anaesthetic, due to the continuous administration of opioids at a set speed for each group. SIGNIFICANCE: Our findings therefore provide preliminary evidence for iTBS targeting the DLPFC to be used to improve postoperative pain management.

Cardiotoxicity from neoadjuvant targeted treatment for breast cancer prior to surgery.

Cancer treatment has been gradually shifting from non-specific cytotoxic agents to molecularly targeted drugs. Breast cancer (BC), a malignant tumor with one of the highest incidence worldwide, has seen a rapid development in terms of targeted therapies, leading to a radical change in the treatment paradigm. However, the use of targeted drugs is accompanied by an increasing rate of deaths due to non-tumor-related causes in BC patients, with cardiovascular complications as the most common cause. Cardiovascular toxicity during antitumor therapy has become a high-risk factor for survival in BC patients. Targeted drug-induced cardiotoxicity exerts a wide range of effects on cardiac structure and function, including conduction disturbances, QT interval prolongation, impaired myocardial contractility, myocardial fibrosis, and hypertrophy, resulting in various clinical manifestations, e.g., arrhythmias, cardiomyopathy, heart failure, and even sudden death. In adult patients, the incidence of antitumor targeted drug-induced cardiotoxicity can reach 50%, and current preclinical evaluation tools are often insufficiently effective in predicting clinical cardiotoxicity. Herein, we reviewed the current status of the occurrence, causative mechanisms, monitoring methods, and progress in the prevention and treatment of cardiotoxicity associated with preoperative neoadjuvant targeted therapy for BC. It supplements the absence of relevant review on the latest research progress of preoperative neoadjuvant targeted therapy for cardiotoxicity, with a view to providing more reference for clinical treatment of BC patients.

Long-Term Impact of the Great Chinese Famine on the Risks of Specific Arrhythmias and Severe Hypertension in the Offspring at an Early Stage of Aging.

Perinatal malnutrition affects postnatal cardiovascular functions. This study used the Great Chinese Famine (GCF) to determine the long-term impact of perinatal undernutrition on hypertension and arrhythmias in older offspring. Subjects (n = 10,065) were divided into an exposed group whose fetal life was in the GCF and an unexposed group. The exposed group showed higher systolic/diastolic pressure, heart rate, and total cholesterol. Perinatal exposure to the GCF was a significant risk to Grade 2 and Grade 3 hypertension (OR = 1.724, 95%CI: 1.441-2.064, p < 0.001; OR = 1.480, 95%CI: 1.050-2.086, p < 0.05) compared to the control. The GCF also increased risks for myocardial ischemia (OR = 1.301, 95%CI: 1.135-1.490, p < 0.001), bradycardia (OR = 1.383, 95%CI: 1.154-1.657, p < 0.001), atrial fibrillation (OR = 1.931, 95%CI: 1.033-3.610, p < 0.05), and atrioventricular block (OR = 1.333, 95%CI: 1.034-1.719, p < 0.05). Total cholesterol, diabetes, and metabolic syndrome were associated with Grade 2 or Grade 3 hypertension after exposure to the GCF; high cholesterol, high BMI, diabetes, metabolic syndrome, and elevated blood pressure were linked to certain types of arrhythmias in exposed offspring. The results first demonstrated perinatal undernutrition was a significant risk factor for the development of Grade 2-3 hypertension and certain arrhythmias in humans. Perinatal undernutrition still significantly impacted cardiovascular systems of the aged offspring even 50 years after the GCF. The results also provided information to a specific population with a history of prenatal undernutrition for early prevention against cardiovascular diseases before aging.

The effectiveness and feasibility of using multi-lead ECG monitoring combined with a programmed intracavitary ECG to complete left bundle branch area pacing.

BACKGROUND: Left bundle branch area pacing (LBBaP) as an alternative method for delivering physiological pacing, is difficult for many primary hospitals that lack the electrophysiological multichannel recorder to carry out. We hope to find a simple and feasible method that combines the multi-lead surface electrocardiogram (ECG) monitoring and the intracavity ECG of the pacing programmer to achieve LBBaP. METHODS: A total of 50 patients with bradycardia indications who attempted permanent pacemaker implantation were included in this study. We referred to multi-lead surface ECG monitoring and pacing system analyzer (PSA), combined with the nine-zone pacing method of the LBBaP, to complete LBBaP. We assessed multiple parameters to verify whether the LBBaP was successfully achieved and used univariable analysis of variance for repeated measures to judge the feasibility and effectiveness of LBBaP without the electrophysiological multichannel recorder. RESULTS: LBBaP was successfully archived without the electrophysiological multichannel recorder in 44 of 50 patients (88%). In the study, paced QRS duration and the stimulus to peak left ventricular activation time (Sti-LVAT) were 117.04 ± 10.34 ms and 71.10 ± 7.91 ms and had no significant changes in the 3-month follow-up. The unipolar pacing threshold and R-wave amplitudes were 0.85 ± 0.32 V and 10.36 ± 5.24 mV at baseline respectively, which also showed stability during the 1-month and 3-month follow-up. During the 3-month follow-up, no lead-related complication was recorded. CONCLUSION: It is effective and feasible to achieve LBBaP combining the multi-lead ECG monitoring and the intracavitary ECG of PSA without the electrophysiological multichannel recorder, which could be an alternative to perform LBBaP.

Dectin-1 Acts as a Non-Classical Receptor of Ang II to Induce Cardiac Remodeling.

BACKGROUND: Cardiac remodeling in heart failure involves macrophage-mediated immune responses. Recent studies have shown that a PRR (pattern recognition receptor) called dectin-1, expressed on macrophages, mediates proinflammatory responses. Whether dectin-1 plays a role in pathological cardiac remodeling is unknown. Here, we identified a potential role of dectin-1 in this disease. METHODS: To model aberrant cardiac remodeling, we utilized mouse models of chronic Ang II (angiotensin II) infusion. In this model, we assessed the potential role of dectin-1 through using D1KO (dectin-1 knockout) mice and bone marrow transplantation chimeric mice. We then used cellular and molecular assays to discover the underlying mechanisms of dectin-1 function. RESULTS: We found that macrophage dectin-1 is elevated in mouse heart tissues following chronic Ang II administration. D1KO mice were significantly protected against Ang II-induced cardiac dysfunction, hypertrophy, fibrosis, inflammatory responses, and macrophage infiltration. Further bone marrow transplantation studies showed that dectin-1 deficiency in bone marrow-derived cells prevented Ang II-induced cardiac inflammation and dysfunction. Through detailed molecular studies, we show that Ang II binds directly to dectin-1, causing dectin-1 homodimerization and activating the downstream Syk (spleen tyrosine kinase)/NF-κB (nuclear factor kappa B) signaling pathway to induce expression of inflammatory and chemoattractant factors. Mutagenesis studies identified R184 in the C-type lectin domain to interact with Ang II. Blocking dectin-1 in macrophages suppresses Ang II-induced inflammatory mediators and subsequent intercellular cross talk with cardiomyocytes and fibroblasts. CONCLUSIONS: Our study has discovered dectin-1 as a new nonclassical receptor of Ang II and a key player in cardiac remolding and dysfunction. These studies suggest that dectin-1 may be a new target for treating hypertension-related heart failure.

A modified mouse model of haemorrhagic transformation associated with tPA administration after thromboembolic stroke.

Objective: To establish a new mouse model of haemorrhagic transformation associated with delayed tissue-type plasminogen activator (tPA) treatment to provide a novel tool to study therapeutic strategies for haemorrhagic transformation. Methods: Male C57BL/6 mice were subjected to carotid artery thrombosis stimulated with ferric chloride. The thrombus was then mechanically detached to induce migration toward the intracranial circulation. To induce haemorrhagic transformation, mice were intravenously injected with 10 mg/kg tPA 4.5 h after the onset of ischaemia and were sacrificed 24 h after tPA treatment. Results: In this new model, administration of tPA 4.5 h after stroke exacerbated the risk of intracerebral haemorrhage. Thrombolysis with tPA also exacerbated cerebral infarction, brain oedema, blood-brain barrier breakdown, and neurological deficits. However, cerebral blood flow was not significantly affected. Conclusion: The present model is reproducible, easy to perform, and mimics the clinical situation of haemorrhagic transformation after tPA treatment in humans. This modified model can be used as a new tool to test experimental drugs for haemorrhagic transformation associated with delayed tPA administration after an ischaemic stroke.

Future trajectory of respiratory infections following the COVID-19 pandemic in Hong Kong.

The accumulation of susceptible populations for respiratory infectious diseases (RIDs) when COVID-19-targeted non-pharmaceutical interventions (NPIs) were in place might pose a greater risk of future RID outbreaks. We examined the timing and magnitude of RID resurgence after lifting COVID-19-targeted NPIs and assessed the burdens on the health system. We proposed the Threshold-based Control Method (TCM) to identify data-driven solutions to maintain the resilience of the health system by re-introducing NPIs when the number of severe infections reaches a threshold. There will be outbreaks of all RIDs with staggered peak times after lifting COVID-19-targeted NPIs. Such a large-scale resurgence of RID patients will impose a significant risk of overwhelming the health system. With a strict NPI strategy, a TCM-initiated threshold of 600 severe infections can ensure a sufficient supply of hospital beds for all hospitalized severely infected patients. The proposed TCM identifies effective dynamic NPIs, which facilitate future NPI relaxation policymaking.

Flavonoids from the roots and rhizomes of Sophoratonkinensis and their in vitro anti-SARS-CoV-2 activity.

Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had caused a global pandemic since 2019, and posed a serious threat to global health security. Traditional Chinese medicine (TCM) has played an indispensable role in the battle against the epidemic. Many components originated from TCMs were found to inhibit the production of SARS-CoV-2 3C-like protease (3CLpro) and papain-like protease (PLpro), which are two promising therapeutic targets to inhibit SARS-CoV-2. This study describes a systematic investigation of the roots and rhizomes of Sophora tonkinensis, which results in the characterization of 12 new flavonoids, including seven prenylated flavanones (1-7), one prenylated flavonol (8), two prenylated chalcones (9-10), one isoflavanone (11), and one isoflavan dimer (12), together with 43 known compounds (13-55). Their structures including the absolute configurations were elucidated by comprehensive analysis of MS, 1D and 2D NMR data, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Compounds 12 and 51 exhibited inhibitory effects against SARS-CoV-2 3CLpro with IC50 values of 34.89 and 19.88 µmol·L-1, repectively while compounds 9, 43 and 47 exhibited inhibitory effects against PLpro with IC50 values of 32.67, 79.38, and 16.74 µmol·L-1, respectively.

Microwave-assisted rapid synthesis of chiral oxazolines.

Chiral oxazoline compounds play an extremely important role in asymmetric synthesis and drug discovery. Herein a simpler, greener and more efficient microwave-assisted protocol to rapidly access chiral oxazolines is developed using aryl nitriles or cyano-containing compounds and chiral ß-amino alcohols as starting materials. The reaction proceeds smoothly in the presence of a recoverable heterogeneous catalyst in either concentrated solution or under solvent-free conditions. The advantages of this method include rapidness, convenience, environmental protection, high atom economy, and excellent yields. The protocol should find wider application in the community in the future.

Flavonoids from the roots and rhizomes of Sophoratonkinensis and their in vitro anti-SARS-CoV-2 activity.

Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had caused a global pandemic since 2019, and posed a serious threat to global health security. Traditional Chinese medicine (TCM) has played an indispensable role in the battle against the epidemic. Many components originated from TCMs were found to inhibit the production of SARS-CoV-2 3C-like protease (3CLpro) and papain-like protease (PLpro), which are two promising therapeutic targets to inhibit SARS-CoV-2. This study describes a systematic investigation of the roots and rhizomes of Sophora tonkinensis, which results in the characterization of 12 new flavonoids, including seven prenylated flavanones (1-7), one prenylated flavonol (8), two prenylated chalcones (9-10), one isoflavanone (11), and one isoflavan dimer (12), together with 43 known compounds (13-55). Their structures including the absolute configurations were elucidated by comprehensive analysis of MS, 1D and 2D NMR data, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Compounds 12 and 51 exhibited inhibitory effects against SARS-CoV-2 3CLpro with IC50 values of 34.89 and 19.88 µmol·L-1, repectively while compounds 9, 43 and 47 exhibited inhibitory effects against PLpro with IC50 values of 32.67, 79.38, and 16.74 µmol·L-1, respectively.

Pharmacological characterization of the small molecule 03A10 as an inhibitor of α-synuclein aggregation for Parkinson's disease treatment.

Aggregation of α-synuclein, a component of Lewy bodies (LBs) or Lewy neurites in Parkinson's disease (PD), is strongly linked with disease development, making it an attractive therapeutic target. Inhibiting aggregation can slow or prevent the neurodegenerative process. However, the bottleneck towards achieving this goal is the lack of such inhibitors. In the current study, we established a high-throughput screening platform to identify candidate compounds for preventing the aggregation of α-synuclein among the natural products in our in-house compound library. We found that a small molecule, 03A10, i.e., (+)-desdimethylpinoresinol, which is present in the fruits of Vernicia fordii (Euphorbiaceae), modulated aggregated α-synuclein, but not monomeric α-synuclein, to prevent further elongation of α-synuclein fibrils. In α-synuclein-overexpressing cell lines, 03A10 (10 µM) efficiently prevented α-synuclein aggregation and markedly ameliorated the cellular toxicity of α-synuclein fibril seeds. In the MPTP/probenecid (MPTP/p) mouse model, oral administration of 03A10 (0.3 mg· kg-1 ·d-1, 1 mg ·kg-1 ·d-1, for 35 days) significantly alleviated behavioral deficits, tyrosine hydroxylase (TH) neuron degeneration and p-α-synuclein aggregation in the substantia nigra (SN). As the Braak hypothesis postulates that the prevailing site of early PD pathology is the gastrointestinal tract, we inoculated α-synuclein preformed fibrils (PFFs) into the mouse colon. We demonstrated that α-synuclein PFF inoculation promoted α-synuclein pathology and neuroinflammation in the gut and brain; oral administration of 03A10 (5 mg· kg-1 ·d-1, for 4 months) significantly attenuated olfactory deficits, α-synuclein accumulation and neuroinflammation in the olfactory bulb and SN. We conclude that 03A10 might be a promising drug candidate for the treatment of PD. 03A10 might be a novel drug candidate for PD treatment, as it inhibits α-synuclein aggregation by modulating aggregated α-synuclein rather than monomeric α-synuclein to prevent further elongation of α-synuclein fibrils and prevent α-synuclein toxicity in vitro, in an MPTP/p mouse model, and PFF-inoculated mice.

Perinatal Fat-Diets Increased Angiotensin II-Mediated Ca2+ through PKC-L-Type Calcium Channel Axis in Resistance Arteries via Agtr1a-Prkcb Gene Methylation.

Perinatal malnutrition affects vascular functions, and calcium is important in vascular regulations. It is unknown whether and how perinatal maternal high-fat diets (MHF)-mediated vascular dysfunction occurs via the angiotensin-PKC-L-type-calcium-channels (LTCC) axis. This study determined angiotensin II (AII) roles in the PKC-LTCC axis in controlling calcium influx in the arteries of offspring after perinatal MHF. Mesenteric arteries (MA) and smooth muscle cells (SMCs) from 5-month-old offspring rats were studied using physiological, ion channel, molecular, and epigenetic analysis. Pressor responses to AII were significantly increased in the free-moving MHF offspring rats. In cell experiments, MA-SMC proliferation was enhanced, and associated with thicker vascular wall in the obese offspring. Imaging analysis showed increase of fluorescence Ca2+ intensity in the SMCs of the MHF group. Angiotensin II receptor (AT1R)-mediated PKC-LTCC axis in vasoconstrictions was altered by perinatal MHF via reduced DNA methylation at specific CpG sites of Agtr1a and Prkcb gene promoters at the transcription level. Accordingly, mRNA and protein expression of AT1R and PKCß in the offspring MA were increased, contributing to enhanced Ca2+ currents and vascular tone. The results showed that DNA methylation resulted in perinatal MHF-induced vascular disorders via altered AT1-PKC-LTCC pathway in resistance arteries of the offspring, providing new insights into the pathogenesis and early prevention/treatments for hypertension in developmental origins.

Effects of Dietary Phytochemicals on DNA Damage in Cancer Cells.

With the increasing incidence of cancer worldwide, the prevention and treatment of cancer have garnered considerable scientific attention. Traditional chemotherapeutic drugs are highly toxic and associated with substantial side effects; therefore, there is an urgent need for developing new therapeutic agents. Dietary phytochemicals are important in tumor prevention and treatment because of their low toxicity and side effects at low concentrations; however, their exact mechanisms of action remain obscure. DNA damage is mainly caused by physical or chemical factors in the environment, such as ultraviolet light, alkylating agents and reactive oxygen species that cause changes in the DNA structure of cells. Several phytochemicals have been shown inhibit the occurrence and development of tumors by inducing DNA damage. This article reviews the advances in phytochemical research; particularly regarding the mechanisms related to DNA damage and provide a theoretical basis for future chemoprophylaxis research.

Cardiovascular imaging in conduction system pacing: What does the clinician need?

Permanent pacemakers are used for symptomatic bradycardia and biventricular pacing (BVP)-cardiac resynchronization therapy (BVP-CRT) is established for heart failure (HF) patients traditionally. According to guidelines, patients' selection for CRT is based on QRS duration (QRSd) and morphology by surface electrocardiogram (ECG). Cardiovascular imaging techniques evaluate cardiac structure and function as well as identify pathophysiological substrate changes including the presence of scar. Cardiovascular imaging helps by improving the selection of candidates, guiding left ventricular (LV) lead placement, and optimization devices during the follow-up. Conduction system pacing (CSP) includes His bundle pacing (HBP) and left bundle branch pacing (LBBP) which is screwed into the interventricular septum. CSP maintains and restores ventricular synchrony in patients with native narrow QRSd and left bundle branch block (LBBB), respectively. LBBP is more feasible than HBP due to a wider target area. This review highlights the role of multimodality cardiovascular imaging including fluoroscopy, echocardiography, cardiac magnetic resonance (CMR), myocardial scintigraphy, and computed tomography (CT) in the pre-procedure assessment for CSP, better selection for CSP candidates, the guidance of CSP lead implantation, and the optimization of devices programming after the procedure. We also compare the different characteristics of multimodality imaging and discuss their potential roles in future CSP implantation.

Chantriolides F-P, Highly Oxidized Withanolides with Hepatoprotective Activity from Tacca chantrieri.

Eleven highly oxidized withanolides, chantriolides F-P (1-11), together with six known analogues (12-17), were isolated from the rhizomes of Tacca chantrieri. Their structures were established on the basis of comprehensive spectroscopic data analysis and comparison with published NMR data, and their absolute configurations were further confirmed by experimental ECD data and single crystal X-ray diffraction analysis. The structures of compounds 5-8 contained a chlorine atom substituted at C-3. Compounds 1 and 12 are a pair of epimers isomerized at C-24 and C-25, while compounds 9 and 16 are isomerized at C-1, C-7, C-24, and C-25. Next, the hepatoprotective effect of all the isolates was evaluated on tert-butyl hydroperoxide (t-BHP)-injured AML12 hepatocytes. Compounds 5-11 and 16 significantly enhanced cell viability. Compound 8 decreased reactive oxygen species accumulation and increased glutathione level in t-BHP injured AML12 hepatocytes through promoting nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2).

Morphological Pattern of Building Clusters in Cold Regions: Evidence from Harbin.

The rapidly changing global conditions of the environment and climate have resulted in higher requirements for urban design. Significant annual temperature variations and large day/night temperature differences in cold-region cities leads to high energy consumption. Therefore, it is challenging to achieve low energy consumption in cold-region cities. Urban morphology focuses on the physical elements of urban areas, reflecting the relationship between the city and its environment and the city's response to natural climatic conditions. Building clusters are common in cold regions due to the extreme climate. Thus, it is crucial to study the energy performance of cities by considering urban morphology. This study focuses on four morphological patterns of building clusters: point, linear, courtyard, and mixed patterns. A case study is conducted in Harbin, a cold-region city in China. Samples of the four morphological patterns are extracted, and GIS analysis and manual labeling are used to analyze the dominant morphological patterns of building clusters in cold regions. Average nearest-neighbor analysis is used to obtain quantitative results and determine the prevalence of different morphological patterns of building clusters in cold regions. This process can be used to determine the dominant patterns of urban building clusters and provide a scientific basis for selecting the morphological patterns of new building clusters in cold regions.

Bioactivity-based molecular networking-guided identification of guttiferone J from Garcinia cambogia as an anti-obesity candidate.

BACKGROUND AND PURPOSE: Pharmacological intervention to induce browning of white adipose tissue provides a promising anti-obesity therapy. The fruits of Garcinia cambogia (Clusiaceae) have been widely applied to manage body weight; however, the chemical principles remain unclear. The current study aims to discover browning inducers from the fruits of G. cambogia and investigate the underlying mechanisms. EXPERIMENTAL APPROACH: The bioactivity-based molecular networking and Oil Red O staining on 3T3-L1 and C3H10T1/2 adipocytes were applied for guided isolation. High-fat diet-induced obese mice were recruited to evaluate the anti-obesity activity. KEY RESULTS: The bioactivity-based molecular networking-guided isolation yielded several polycyclic polyprenylated acylphloroglucinols from the fruits of G. cambogia with lipid-lowering effect in adipocytes, including guttiferone J (GOJ), garcinol and 14-deoxygarcinol. As the most potent one, GOJ (10 µM) reduced lipid accumulation by 70% and 76% in 3T3-L1 and C3H10T1/2 adipocytes, respectively. Furthermore, GOJ (2.5-10 µM) increased the expression of the deacetylase sirtuin 3 (SIRT3) and activated it, which, in turn, reduced the acetylation level of PPARγ coactivator-1α to boost mitochondrial biogenesis and promoted uncoupling protein 1 expression to enhance thermogenesis, resulting in browning of adipocytes. In high-fat diet-induced-obese mice, GOJ (10 and 20 mg·kg-1 ·day-1 for 12 weeks) protected against adiposity, hyperlipidaemia, insulin resistance and liver lipotoxicity, through boosting SIRT3-mediated browning of inguinal adipose tissue. CONCLUSION AND IMPLICATIONS: GOJ represents a new scaffold of thermogenic inducer, which is responsible for the anti-obesity property of G. cambogia and can be further developed as a candidate for treating obesity and its related disorders.

Underlying mechanisms of acupuncture therapy on polycystic ovary syndrome: Evidences from animal and clinical studies.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder among women of reproductive age. Current standard treatment includes lifestyle change, oral pharmacological agents, and surgical modalities. However, the efficacy of current therapies is less than satisfactory. Clinical evidence has shown that acupuncture is effective for regulating hormone levels, promoting ovulation, and attenuating insulin resistance in patients with PCOS. Acupuncture may affect the production of ß-endorphin, which may lead to gonadotropin-releasing hormone secretion and then affect ovulation, menstrual cycle, and fertility. The mechanism of acupuncture for patients with PCOS has not been comprehensively reviewed so far. Better understanding of the mechanisms of acupuncture would help popularize the use of acupuncture therapy for patients with PCOS. In this narrative review, we aimed to overview the potential mechanisms and evidence-based data of acupuncture on PCOS, and analyze the most frequently used acupoints based on animal and clinical studies. The results of this study will contribute to a better understanding of the current situation in this field.