Epigenetic activation of cytochrome P450 1A2 sensitizes hepatocellular carcinoma cells to sorafenib.

Cytochrome P450 1A2 (CYP1A2) is a known tumor suppressor in hepatocellular carcinoma (HCC), but its expression is repressed in HCC and the underlying mechanism is unclear. In this study, we investigated the epigenetic mechanisms of CYP1A2 repression and potential therapeutic implications. In HCC tumor tissues, the methylation rates of CYP1A2 CpG island (CGI) and DNMT3A protein levels were significantly higher, and there was a clear negative correlation between DNMT3A and CYP1A2 protein expression. Knockdown of DNMT3A by siRNA significantly increased CYP1A2 expression in HCC cells. Additionally, treating HCC cells with decitabine (DAC) resulted in a dose-dependent upregulation of CYP1A2 expression by reducing the methylation level of CYP1A2 CGI. Furthermore, we observed a decreased enrichment of H3K27Ac in the promoter region of CYP1A2 in HCC tissues. Treatment with the trichostatin A (TSA) restored CYP1A2 expression in HCC cells by increasing H3K27Ac levels in the CYP1A2 promoter region. Importantly, combination treatment of sorafenib with DAC or TSA resulted in a leftward shift of the dose-response curve, lower IC50 values, and reduced colony numbers in HCC cells. Our findings suggest that hypermethylation of the CGI at the promoter, mediated by the high expression of DNMT3A, and hypoacetylation of H3K27 in the CYP1A2 promoter region, leads to CYP1A2 repression in HCC. Epigenetic drugs DAC and TSA increase HCC cell sensitivity to sorafenib by restoring CYP1A2 expression. Our study provides new insights into the epigenetic regulation of CYP1A2 in HCC and highlights the potential of epigenetic drugs as a therapeutic approach for HCC. Significance Statement This study marks the first exploration of the epigenetic mechanisms underlying CYP1A2 suppression in hepatocellular carcinoma (HCC). Our findings reveal that heightened Dnmt3a expression induces hypermethylation of the CGI at the promoter, coupled with diminished H3K27Ac levels, resulting in the repression of CYP1A2 in HCC. The use of epigenetic drugs such as decitabine (DAC) and trichostatin A (TSA) emerges as a novel therapeutic avenue, demonstrating their potential to restore CYP1A2 expression and enhance sorafenib sensitivity in HCC cells.

The neural representations of valence transformation in indole processing.

Indole is often associated with a sweet and floral odor typical of jasmine flowers at low concentrations and an unpleasant, animal-like odor at high concentrations. However, the mechanism whereby the brain processes this opposite valence of indole is not fully understood yet. In this study, we aimed to investigate the neural mechanisms underlying indole valence encoding in conversion and nonconversion groups using the smelling task to arouse pleasantness. For this purpose, 12 conversion individuals and 15 nonconversion individuals participated in an event-related functional magnetic resonance imaging paradigm with low (low-indole) and high (high-indole) indole concentrations in which valence was manipulated independent of intensity. The results of this experiment showed that neural activity in the right amygdala, orbitofrontal cortex and insula was associated with valence independent of intensity. Furthermore, activation in the right orbitofrontal cortex in response to low-indole was positively associated with subjective pleasantness ratings. Conversely, activation in the right insula and amygdala in response to low-indole was positively correlated with anticipatory hedonic traits. Interestingly, while amygdala activation in response to high-indole also showed a positive correlation with these hedonic traits, such correlation was observed solely with right insula activation in response to high-indole. Additionally, activation in the right amygdala in response to low-indole was positively correlated with consummatory pleasure and hedonic traits. Regarding olfactory function, only activation in the right orbitofrontal cortex in response to high-indole was positively correlated with olfactory identification, whereas activation in the insula in response to low-indole was negatively correlated with the level of self-reported olfactory dysfunction. Based on these findings, valence transformation of indole processing in the right orbitofrontal cortex, insula, and amygdala may be associated with individual hedonic traits and perceptual differences.

Treatment and prevention of pigeon diarrhea through the application of Lactobacillus SNK-6.

In the pigeon industry, treating and preventing diarrhea is vital because it is a serious health problem for pigeons. This study investigated the incidence of diarrhea in 3 pigeon farms in Shanghai, and analyzed the microflora through 16S rDNA high-throughput sequencing. Four strains of Escherichia coli (E. coli) isolated from pigeon diarrhea feces were administered via gavage to healthy pigeons, with each pigeon receiving 2 × 108 CFU. Pigeons that developed diarrhea after E. coli challenge were treated with 3 g of Lactobacillus salivarius SNK-6 (L. salivarius SNK-6) health sand (1.6 × 107 CFU/g). Then, a mass feeding experiment expanded to 688 pairs of pigeons with 3 replicates, each receiving 3 g of health sand containing L. salivarius SNK-6 (1.6 × 107 CFU/g) every 2 wk, and fecal status monitored and recorded. The study found that the relative abundance of the Lactobacillus genus and L. salivarius in feces from pigeons with diarrhea was significantly lower than in normal pigeon feces (P < 0.05). In contrast, E. coli showed a higher abundance and diversity in feces from pigeons with diarrhea than in normal feces (P < 0.05). Three out of the 4 isolated E. coli strains caused pigeon diarrhea, resulting in a significant reduction in microbial diversity in fecal samples (P < 0.05). Both the small group attack experiment and the mass-fed additive experiment in pigeon farms demonstrated that feeding L. salivarius SNK-6 effectively cured and prevented diarrhea. Pigeons fed with L. salivarius SNK-6 exhibited no diarrhea, while the control group had a 10% diarrhea rate. In summary, a deficiency of Lactobacillus or a high abundance of E. coli in the intestine could easily cause pigeon diarrhea. Feeding L. salivarius SNK-6 could treat pigeon diarrhea, and continuous supplementation could maintain stable preventive effects.

Omental fibroma combined with right indirect inguinal hernia masquerades as a scrotal tumor: A case report.

BACKGROUND: The most common causes of scrotal enlargement in patients include primary tumor of the scrotum, inflammation, hydrocele of the tunica vaginalis, and indirect inguinal hernia; scrotal enlargement caused by external tumors of the scrotum is rare. The patient had both a greater omentum tumor and an inguinal hernia, and the tumor protruded into the scrotum through the hernia sac, which is even rarer. Moreover, omental tumors are mostly metastatic, and primary omental fibroma is rare. CASE SUMMARY: Here, we report a rare case of a 25-year-old young man with scrotal enlargement and pain for 3 months. Preoperative examination and multidisciplinary discussions considered intra-abdominal tumor displacement and inguinal hernia, and intraoperative exploration confirmed that the greater omentum tumor protruded into the scrotum. Therefore, tumor resection and tension-free inguinal hernia repair were performed. The final diagnosis was benign fibroma of the greater omentum accompanied by an indirect inguinal hernia. CONCLUSION: This unusual presentation of a common inguinal hernia disease illustrates the necessity of performing detailed history taking, physical examination, and imaging before surgery.

Pharmacokinetic and pharmacodynamic studies of nicotine in rat brain: a simultaneous investigation of nicotine metabolites and the release of neurotransmitters in vivo.

Introduction: The body's ability to metabolize nicotine and the disposition of nicotine in the brain are important determinants of its exposure. Limited knowledge about the near real-time changes of neurochemicals during the brain nicotine metabolic process hinders the recognition of its multiple neuropharmacological effects. Methods: An online microdialysis coupled with UHPLC-HRMS/MS method for the in vivo multi-analysis of nicotine metabolites and several neurotransmitters in rat brain was developed. Whether the systemic modulation of metabolic enzyme CYP2B would modulate nicotine pharmacokinetics and local neurochemical effects was further investigated. Results: The dynamic profiles of over 10 nicotine metabolites and neurotransmitters were simultaneously obtained after a single injection of nicotine (2 mg·kg-1, i.p.) using the new method. Proadifen pretreatment (50 mg·kg-1·d-1, i.p., 4 days) caused significant inhibition of brain CYP2B1 activity. When exposed to nicotine, the brain C max of nicotine was 1.26 times higher and the levels of nicotine metabolites, nornicotine, and nicotine-N-oxide, were decreased by 85.3% and 34.4% in proadifen-pretreated rats. The higher level of brain nicotine induced a greater release of dopamine, serotonin, glutamate, and γ-amino-butyric acid in the nucleus accumbens. The concentrations of nicotine and dopamine were positively correlated, and the average levels of γ-amino-butyric acid and serotonin were 2.7 and 1.2 times higher, respectively, under the inhibition of nicotine metabolism. Discussion: These results demonstrated that inhibiting nicotine metabolism in rats can enhance the residence of brain nicotine and its local neurotransmitter effects. The metabolic activity of nicotine under different physiological conditions could regulate nicotine's bioavailability and its resulting pharmacology.

Quinoline Bridging Hyperconjugated Covalent Organic Framework as Solid-Phase Microextraction Coating for Ultrasensitive Determination of Phthalate Esters in Water Samples.

Phthalate esters (PAEs) are widely distributed in the environment, and this has caused serious health and safety concerns. Development of rapid and ultrasensitive identification and analysis methods for phthalate esters is urgent and highly desirable. In this work, a novel nitrogen-rich covalent organic framework (N-TTI) derived quinoline bridging covalent organic framework (N-QTTI) was fabricated and used as a solid-phase microextraction (SPME) coating for the ultrasensitive determination of phthalate esters in water samples. The physical and chemical properties of N-QTTI were investigated sufficiently. The N-QTTI-coated fiber demonstrates a superior enrichment performance than either the N-TTI-coated fiber or commercial fibers under the optimized SPME conditions. For the first time, we propose a semi-immersion strategy for the extraction of PAEs from water samples based on N-QTTI-coated SPME fibers. Combined with gas chromatography-mass spectrometry (GC-MS), the developed method N-QTTI-SPME-GC-MS exhibits a wide linear range with a satisfactory linearity (R2 ≥ 0.995). The limits of detection (LOD, S/N = 3) and the limits of quantification (LOQs, S/N = 10) were 0.17-1.70 and 0.57-5.60 ng L-1, respectively. The repeatability of the new method was examined using relative standard deviations (RSDs) between intraday and interday data, which were 0.38-7.98% and 1.22-6.60%, respectively. The spiked recoveries at three levels of 10, 100, and 1000 ng L-1 were in the range of 90.0-106.2% with RSDs of less than 7.48%. The enrichment factors ranged from 291 to 17180. When compared to previously published works, the LODs of the newly established method were improved 5-5400 times, and the enrichment factors were increased by at least 8 times. The absorption mechanism was investigated by X-ray photoelectron spectroscopy and noncovalent interaction force analysis. The technique was successfully employed for detecting PAEs in water samples.

Rapid and sensitive determination of free fatty acids based on in-source microdroplet-driven derivatization coupled with high-resolution mass spectrometry.

Accurate and sensitive measurements of free fatty acids (FFAs) in biological samples are valuable for diagnosing and prognosing diseases. In this study, an in-source microdroplet derivation strategy combined with high-resolution mass spectrometry was developed to analyze FFAs in lipid extracts of biological samples directly. FFAs were rapidly derivated with 2-picolylamine (PA) in the microdroplet which is derived by electrospray. With the proposed method, twelve typical FFAs were determined reliably with high sensitivity and acceptable linearities (R2 ≥ 0.94). The LODs and LOQs for the twelve FFAs were 9-76 pg mL-1 and 30-253 pg mL-1, respectively. The developed method was applied to analyze the alteration of FFAs in liver and kidney samples of rats induced by perfluorooctane sulfonate (PFOS) exposure. The good results demonstrate that the established analysis technique is dependable and has promising applications in detecting FFAs associated with complex biological samples.

A flexible electrochemical glucose sensing platform based on an electrospun PVA mat covered with in situ grown silver nanoparticles and a mixed self-assembled monolayer of glucose oxidase and ferrocene.

An electrochemical glucose sensor based on flexible materials is significant for wearable devices used for real-time health monitoring and diagnosis. However, applying flexible electrodes involves complex fabrication processes and might reduce detection sensitivity. To overcome these obstacles, we herein report a novel strategy for preparing a highly flexible enzyme electrode based on an electrospun poly(vinyl alcohol) (PVA) mat decorated with in situ grown silver nanoparticles (nano-Ag) for electrochemical glucose sensing. Ferrocene (Fc) was selected as an electron acceptor for glucose oxidase (GOD) in order to minimize the influence of oxygen. Electron transfer between GOD and Fc was facilitated by confining them within a mixed self-assembled monolayer (SAM) formed on a thin layer of gold deposited on top of the PVA/nano-Ag film. Nano-Ag was found to significantly increase the surface area of the electrode and improve the stability of electrode conductivity during tensile deformation. Electrochemical glucose detection was performed by chronoamperometry in the electroactivity domain of ferrocene, and good linearity (R2 = 0.993) was obtained in the range of 0.2-7 mM with a detection limit of 0.038 mM and a relative standard deviation (RSD) of 1.45% (n = 6). After being stuck to a bendable PDMS slice and bent, respectively, at 30° and 60° 50 times, the electrode showed slight changes in detection results (<4.78%), which remained within 8% when the bending angle increased to 90°. With its high flexibility, good detection performance, and convenient fabrication process, the proposed enzyme electrode showed good potential as a flexible platform for wearable glucose sensing systems.

ROS-related disruptions to cochlear hair cell and stria vascularis consequently leading to radiation-induced sensorineural hearing loss.

AIMS: Radiation-induced sensorineural hearing loss (RISNHL) is one of the major side effects of radiotherapy (RT) for head and neck cancers. Currently, no effective clinical treatment or prevention is available for RISNHL. This study thus aimed to investigate the cochlear pathology so that the underlying mechanisms of RISNHL may be elucidated, consequently paving the way for potential protective strategies to be developed. RESULTS: Functional and morphological impairment in the stria vascularis (SV) was observed after irradiation (IR), as indicated by endocochlear potential (EP) reduction, hyperpermeability and SV atrophy. The expression of zonulae occludins-1 (ZO-1) was found to have decreased after IR. The loss of outer hair cells (OHCs) occurred later than SV damage. The disruption to the SV and OHCs could be attributed to ROS-related damage. In addition, EP shifts and the loss of OHCs were reduced when ROS was reduced by N-acetylcysteine (NAC) in C57BL/6 mice, attenuating auditory threshold shifts. INNOVATION: The damage to the SV was found to occur before OHC loss. ROS-related damage accounted for SV damage and OHC loss. The incidences of SV damage and OHC loss were decreased through ROS modulation by NAC, subsequently preventing RISNHL, suggesting the possible role of NAC as a possible protective agent against RISNHL. CONCLUSION: The findings from this study suggest oxidative stress-induced early SV injury and late OHC loss to be the key factors leading to RISNHL. NAC prevents IR-induced OHC loss, and attenuates auditory brainstem response (ABR) and EP shifts by regulating the level of oxidative stress.

Thermal/Redox-triggered release of pyrazinic functional molecules by coordination polymers with luminescence monitoring ability.

Storage of volatile active molecules, along with the prolongation of their specific functions, requires the use of regulatable carriers. Pyrazine derivatives are highly volatile compounds with a broad application owing to their flavoring, pharmaceutical, antimicrobial, antiseptic, and insecticidal properties. In this study, pyrazines were stored by coordinating them with cuprous iodide to easily generate a series of luminescent coordination polymer (CP)-based carriers. The CPs could respond to thermal-redox stimuli and manipulate pyrazine release by breaking the labile Cu-N bonds when triggered by the two stimuli. Moreover, the release process could be visualized by decreased luminescence caused by the gradual decomposition of CP structures. The loading efficiencies ranged from 31% to 38%, and the controlled release behaviors accord with the zero-order kinetics. This work is the first to prove that CPs could function as dual stimuli-mediated delivery systems, which hold the potential to control the release and strengthen the usability of functional molecules.

Pyridine N-Oxide-Promoted Cobalt-Catalyzed Dioxygen-Mediated Methane Oxidation.

The partial oxidation of methane with O2 is significant due to its potential of providing abundant chemical feedstock. Only a few examples realized this type of reaction in homogeneous solvent systems, most of which are in low efficiency. Herein, we present a pyridine N-oxide-promoted cobalt-catalyzed O2-mediated methane oxidation to produce methylene bis(trifluoroacetate) with productivity over 500 molester molmetal-1 h-1.

Influence of macrophage polarization in herniated nucleus pulposus tissue on clinical efficacy after lumbar discectomy.

Background: Low back pain or sciatic pain because of lumbar intervertebral disc herniation (LDH) is caused by mechanical compression and/or an inflammatory component on the nerve root. However, it is difficult to define to what extent each component contributes to the pain. This study attempted to explore the effects of macrophage polarization on clinical symptoms in patients experiencing LDH after surgery, and investigated the association between macrophage cell percentages and clinical efficacy. Methods: This study retrospectively harvested nucleus pulposus (NP) tissue samples from 117 patients. Clinical symptoms and efficacy using the visual analog scale (VAS) and Oswestry Disability Index (ODI) were evaluated at different time points preoperatively and postoperatively. CD68, CCR7, CD163, and CD206 were selected as macrophage phenotypic markers. Results: Seventy-six samples showed positive expression of macrophage markers in NP samples of patients with LDH, whereas 41 patients displayed negative results. No significant differences were detected between the two groups, involvement of several demographic data, and preoperative clinical findings. With respect to the macrophage-positive group, no significant correlation was detected between the positive rate of the four markers and the VAS score or ODI after surgery. However, patients with NP samples positive for CD68 and CCR7 expression showed significantly lower VAS scores 1 week after surgery compared with those in the negative group. Moreover, the improvement in VAS score showed a strong positive correlation with CD68- and CCR7-positive cell percentages. Conclusions: Our results indicated that pro-inflammatory M1 macrophages may be associated with the reduction of chronic pain after surgery. Therefore, these findings contribute to better personalized pharmacological interventions for patients with LDH, considering the heterogeneity of pain.

Zn-Mediated Scalable Synthesis of Trifluoromethylphosphines from Phosphine Chlorides and CF3Br.

Trifluoromethylphosphines represent a rare kind of phosphine with unique electronic withdrawing properties, which lead to some distinctive reactivities. The reported TFMPhos, products from nucleophilic or electrophilic trifluoromethylation of substrates, requiring one or more steps and prepared from phosphine chlorides, are very limited in structure diversity. Herein, we report a convenient and scalable (up to 100 mmol) recipe to synthesize diverse trifluoromethylphosphines via direct radical trifluoromethylation of phosphine chlorides with CF3Br in the presence of zinc powder.

Brain distribution and metabolic profiling of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in rats investigated by UHPLC-HRMS/MS following peripheral administration.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is known to be a tobacco-specific N-nitrosamine and has peripheral carcinogenic properties. It can also induce oxidative stress, glial cell activation, and neuronal damage in the brain. However, the distribution and metabolic characteristics of NNK in the central nervous system are still unclear. Here, a sensitive and effective UHPLC-HRMS/MS method was established to identify and investigate the metabolites of NNK and their distribution in the rat brain. In addition, the pharmacokinetic profiles were simultaneously investigated via blood-brain synchronous microdialysis. NNK and its seven metabolites were well quantified in the hippocampus, cortex, striatum, olfactory bulb, brain stem, cerebellum, and other regions of rat brain after peripheral exposure (5 mg/kg, i.p.). The average content of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in all brain regions was at least threefold higher than that of NNK, indicating a rapid carbonyl reduction of NNK in the brain. Lower concentrations of pyridine N-oxidation products in the cortex, olfactory bulb, hippocampus, and striatum might be related to the poor detoxification ability in these regions. Compared to α-methyl hydroxylation, NNK and NNAL were more inclined to the α-methylene hydroxylation pathway. Synchronous pharmacokinetic results indicated that the metabolic activity of NNK in the brain was different from that in the blood. The mean α-hydroxylation ratio in the brain and blood was 0.037 and 0.161, respectively, which indicated poor metabolic activity of NNK in the central nervous system.

Untargeted Metabolomics Using UHPLC-HRMS Reveals Metabolic Changes of Fresh-Cut Potato during Browning Process.

Surface browning plays a major role in the quality loss of fresh-cut potatoes. Untargeted metabolomics were used to understand the metabolic changes of fresh-cut potato during the browning process. Their metabolites were profiled by ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UHPLC-HRMS). Data processing and metabolite annotation were completed by Compound Discoverer 3.3 software. Statistical analysis was applied to screen the key metabolites correlating with browning process. Fifteen key metabolites responsible for the browning process were putatively identified. Moreover, after analysis of the metabolic causes of glutamic acid, linolenic acid, glutathione, adenine, 12-OPDA and AMP, we found that the browning process of fresh-cut potatoes was related to the structural dissociation of the membrane, oxidation and reduction reaction and energy shortage. This work provides a reference for further investigation into the mechanism of browning in fresh-cut products.

Conversion surgery for advanced hepatocellular carcinoma after combination treatment of lenvatinib and camrelizumab: a case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive malignancy with high morbidity and mortality. Conversion therapy can improve surgical resection rate and prolong survival time for patients with advanced HCC. We show that combination therapy with lenvatinib and camrelizumab is a novel approach to downstage unresectable HCC. CASE PRESENTATION: A 49-year-old man was diagnosed with massive HCC with hilar lymph node and lung metastases. Since radical resection was not feasible, lenvatinib and camrelizumab were administered as first-line therapy. After 10 cycles of camrelizumab and continuous oral administration of lenvatinib, the tumor exhibited striking shrinkage in volume indicating a partial radiological response, accompanied by a reduction in the alpha-fetoprotein levels, followed by salvage resection. Intriguingly, an improvement in predictive biomarkers, like lactate dehydrogenase (LDH) and neutrophil-to-lymphocyte ratio (NLR), was observed. Notably, the pathological examination found high levels of necrosis in the resected tumor, and flow cytometry analysis indicated a significant increase in the ratio of CD5+ and CD5- B lymphocytes in the peripheral blood. After the treatment, the overall survival period was over 24 months, and no recurrence was observed 17-month post-surgery. CONCLUSIONS: A combination of lenvatinib and camrelizumab may be a new conversion therapy for initially unresectable HCC to resectable HCC, thus contributing to improve the disease prognosis. In addition, the combination regimen could cause an activated immune response, and LDH, NLR, and CD5+ B-cell levels might be predictors for immunotherapy efficacy.

Nicotine alleviates MPTP-induced nigrostriatal damage through modulation of JNK and ERK signaling pathways in the mice model of Parkinson's disease.

Introduction: Nicotine (Nic) has previously been proven to reduce neurodegeneration in the models of Parkinson's disease (PD). The present study is intended to investigate the detailed mechanisms related to the potential neuroprotective effects of Nic in vivo. Methods: We established a PD model using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced C57BL6 mice (25 mg/kg/d, 5 d, i.p.) to investigate the neuropharmacological modulation of Nic pretreatment (2.5 mg/kg/d, 5 d, i.p., 30 min before MPTP injection) from the perspectives of neurobehavioral assessment, the pathological alterations, microglial cell inflammation and MAPK signaling pathways in specific brain regions. Results: The open field test, elevated plus maze, rotarod and traction test suggested that Nic pretreatment could significantly improve MPTP-induced motor impairment and had an anxiolytic effect. Nic was found to improve neuroapoptosis, enhance tyrosine hydroxylase activity, and reduce the accumulation of the phosphorylated α-synuclein in the substantia nigra and striatal regions of PD mice by TUNEL and immunohistochemical assays. Immuno-fluorescent method for labeling Iba1 and CD68 indicated that Nic remarkably alleviates the activation of microglia which represents the M1 polarization state in the mice brain under MPTP stimulation. No significant difference in the expression of p38/MAPK pathway was found in the nigrostriatal regions, while Nic could significantly inhibit the elevated p-JNK/JNK ratio and increase the declined p-ERK/ERK ratio in the substantia nigra of MPTP-exposed brains, which was further confirmed by the pretreatment of CYP2A5 inhibitor to decline the metabolic activity of Nic. Discussion: The molecular signaling mechanism by which Nic exerts its neuroprotective effects against PD may be achieved by regulating the JNK and ERK signaling pathways in the nigra-striatum related brain regions.

Copper(I)-Iodide Clusters as Carriers for Regulating and Visualizing Release of Aroma Molecules.

Achieving the controlled release of functional substances is indispensable in many aspects of life. Especially for the aroma molecules, their effective delivery of flavor and fragrance is challenging. Here, selected pyridines, as highly volatile odorants, were individually coordinated with copper(I) iodide (CuII) via a straightforward one-pot synthesis method, rapidly forming pure or even crystalline CuII cluster-based profragrances at room temperature. The obtained profragrances enabled the stable and high loading of volatile fragrances under ambient conditions and guaranteed their long-lasting release during heating. Furthermore, the intrinsic emission luminescence of these solid-state profragrances decayed along with the aroma release, which can serve as an additional indicator for monitoring the delivery process. This research sets a precedent for using CuII clusters as dual-purpose release agents and greatly expands their potential applications.

A case of combined oxidative phosphorylation deficiency 32 caused by MRPS34 gene variation and literature review / 中华儿科杂志

Objective: To investigate the clinical features and genetic features of combined oxidative phosphorylation deficiency 32 (COXPD32) caused by MRPS34 gene variation. Methods: The clinical data and genetic test of a child with COXPD32 hospitalized in the Department of Neurology, Children's Hospital, Capital Institute of Pediatrics in March 2021 were extracted and analyzed. A literature search was implemented using Wanfang, China biology medicine disc, China national knowledge infrastructure, ClinVar, human gene mutation database (HGMD) and Pubmed databases with the key words "MRPS34" "MRPS34 gene" and "combined oxidative phosphorylation deficiency 32" (up to February 2023). Clinical and genetic features of COXPD32 were summarized. Results: A boy aged 1 year and 9 months was admitted due to developmental delay. He showed mental and motor retardation, and was below the 3rd percentile for height, weight, and head circumference of children of the same age and gender. He had poor eye contact, esotropia, flat nasal bridge, limbs hypotonia, holding instability and tremors. In addition, Grade Ⅲ/6 systolic murmur were heard at left sternal border. Arterial blood gases suggested that severe metabolic acidosis with lactic acidosis. Brain magnetic resonance imaging (MRI) showed multiple symmetrical abnormal signals in the bilateral thalamus, midbrain, pons and medulla oblongata. Echocardiography showed atrial septal defect. Genetic testing identified the patient as a compound heterozygous variation of MRPS34 gene, c.580C>T (p.Gln194Ter) and c.94C>T (p.Gln32Ter), with c.580C>T being the first report and a diagnosis of COXPD32. His parents carried a heterozygous variant, respectively. The child improved after treatment with energy support, acidosis correction, and "cocktail" therapy (vitaminB1, vitaminB2, vitaminB6, vitaminC and coenzyme Q10). A total of 8 cases with COXPD32 were collected through 2 English literature reviews and this study. Among the 8 patients, 7 cases had onset during infancy and 1 was unknown, all had developmental delay or regression, 7 cases had feeding difficulty or dysphagia, followed by dystonia, lactic acidosis, ocular symptoms, microcephaly, constipation and dysmorphic facies(mild coarsening of facial features, small forehead, anterior hairline extending onto forehead,high and narrow palate, thick gums, short columella, and synophrys), 2 cases died of respiratory and circulatory failure, and 6 were still alive at the time of reporting, with an age range of 2 to 34 years. Blood and (or) cerebrospinal fluid lactate were elevated in all 8 patients. MRI in 7 cases manifested symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia. Urine organic acid test were all normal but 1 patient had alanine elevation. Five patients underwent respiratory chain enzyme activity testing, and all had varying degrees of enzyme activity reduction. Six variants were identified, 6 patients were homozygous variants, with c.322-10G>A was present in 4 patients from 2 families and 2 compound heterozygous variants. Conclusions: The clinical phenotype of COXPD32 is highly heterogenous and the severity of the disease varies from development delay, feeding difficulty, dystonia, high lactic acid, ocular symptoms and reduced mitochondrial respiratory chain enzyme activity in mild cases, which may survive into adulthood, to rapid death due to respiratory and circulatory failure in severe cases. COXPD32 needs to be considered in cases of unexplained acidosis, hyperlactatemia, feeding difficulties, development delay or regression, ocular symptoms, respiratory and circulatory failure, and symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia, and genetic testing can clarify the diagnosis.

A case-control study on the association between a healthy lifestyle and obesity among adult twins in Shanghai / 中华流行病学杂志

Objective: To investigate the associations between the numbers of healthy lifestyles and overweight/obesity and abdominal obesity in adult twins in Shanghai. Methods: Based on the Shanghai Twin Registry System Phase Ⅱ survey data in 2017-2018, a case-control study was conducted to analyze the association between healthy lifestyles and obesity and further adjusted for confounders by a co-twin control study. Results: A total of 7 864 adult twins (3 932 pairs) were included. In the co-twin case-control analysis for monozygotic twins, compared with participants with 0 to 2 healthy lifestyles, those with 3 and 4 to 5 healthy lifestyles had a 49% (OR=0.51, 95%CI: 0.28-0.93) and 70% (OR=0.30, 95%CI: 0.13-0.69) lower risk of overweight/obesity, respectively, and a 17% (OR=0.83, 95%CI: 0.44-1.57) and 66% (OR=0.34, 95%CI: 0.14-0.80) lower risk of abdominal obesity, respectively. For each additional healthy lifestyle, the risk of developing overweight/obesity was reduced by 41% (OR=0.59, 95%CI: 0.42-0.85), and the risk of developing abdominal obesity was reduced by 37% (OR=0.63, 95%CI: 0.44-0.90). Conclusion: An increasing number of healthy lifestyles was associated with a marked decreased risk for both overweight/obesity and abdominal obesity.