Effect of the modified painless blistering moxibustion with wheat-grain sized moxa cone on cough variant asthma of pathogenic wind attacking the lung: a randomized controlled trial. / æ”¹è‰¯æ— ç—›éº¦ç²’åŒ–è„“ç¸æ²»ç–—é£Žé‚ªçŠ¯è‚ºåž‹å’³å—½å˜å¼‚æ€§å“®å–˜ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the clinical effect of the modified painless blistering moxibustion with wheat-grain sized moxa cone on cough variant asthma (CVA) differentiated as pathogenic wind attacking the lung and explore the influences on eosinophil count (EOS) in the peripheral blood and the content of interleukin-4 (IL-4) and tumor necrosis factor-α (TNF-α) in the serum of patients. METHODS: Ninety-two patients with CVA of pathogenic wind attacking the lung were randomly divided into an observation group and a control group, 46 cases in each group. In the observation group, the modified painless blistering moxibustion with wheat-grain sized moxa cone was applied to the unilateral Feishu (BL 13), Gaohuang (BL 43) and Zusanli (ST 36) in each session of treatment, once every 3 days. In the control group, budesonide and formoterol powder inhaler was delivered, 4.5 µg per inhalation, once every half an hour after breakfast and dinner; one more time of inhalation needed if the symptoms were not well controlled, but less than 6 times of inhalation per day. The duration of treatment was 8 weeks in both groups. Separately, before and after treatment, and during the 1-month follow-up after treatment completion, the score of the symptoms of traditional Chinese medicine (TCM) was observed in the two groups; using the lung function detector, the indexes of pulmonary function (forced expiratory volume in one second [FEV1], FEV1/forced vital capacity [FVC] and peak expiratory flow [PEF]) were determined, and the count of EOS in the peripheral blood and the content of IL-4 and TNF-α in the serum were determined before and after treatment; and the clinical effect was compared between the two groups. RESULTS: After treatment and in follow-up, the TCM symptom scores were decreased compared with those before treatment in the two groups (P<0.05), and the score in the observation group was lower than that of the control group in follow-up (P<0.05). After treatment, FEV1, FEV1/FVC and PEF were increased when compared with those before treatment in the two groups (P<0.05), and the count of EOS in the peripheral blood and the content of IL-4 and TNF-α in the serum were reduced (P<0.05); there was no statistical difference in these indexes between the two groups (P>0.05). After treatment, the total effective rate of the observation group was 95.7% (44/46), which was not different statistically in comparison with the control group (93.5% [43/46], P>0.05). In the follow-up, the total effective rate of the observation group was 95.7% (44/46), which was higher than that of the control group (78.3% [36/46], P<0.05). CONCLUSIONS: The modified painless blistering moxibustion with wheat-grain sized moxa cone may ameliorate the symptoms of CVA of pathogenic wind attacking the lung and improve the pulmonary functions, which is probably related to the regulation of the count of EOS in the peripheral blood and the content of IL-4 and TNF-α in the serum, thereby, reducing the inflammatory response.

Neuronal and Molecular Mechanisms Underlying Chronic Pain and Depression Comorbidity in the Paraventricular Thalamus.

Patients with chronic pain often develop comorbid depressive symptoms, which makes the pain symptoms more complicated and refractory. However, the underlying mechanisms are poorly known. Here, in a repeated complete Freund's adjuvant (CFA) male mouse model, we reported a specific regulatory role of the paraventricular thalamic nucleus (PVT) glutamatergic neurons, particularly the anterior PVT (PVA) neurons, in mediating chronic pain and depression comorbidity (CDC). Our c-Fos protein staining observed increased PVA neuronal activity in CFA-CDC mice. In wild-type mice, chemogenetic activation of PVA glutamatergic neurons was sufficient to decrease the 50% paw withdrawal thresholds (50% PWTs), while depressive-like behaviors evaluated with immobile time in tail suspension test (TST) and forced swim test (FST) could only be achieved by repeated chemogenetic activation. Chemogenetic inhibition of PVA glutamatergic neurons reversed the decreased 50% PWTs in CFA mice without depressive-like symptoms and the increased TST and FST immobility in CFA-CDC mice. Surprisingly, in CFA-CDC mice, chemogenetically inhibiting PVA glutamatergic neurons failed to reverse the decrease of 50% PWTs, which could be restored by rapid-onset antidepressant S-ketamine. Further behavioral tests in chronic restraint stress mice and CFA pain mice indicated that PVA glutamatergic neuron inhibition and S-ketamine independently alleviate sensory and affective pain. Molecular profiling and pharmacological studies revealed the 5-hydroxytryptamine receptor 1D (Htr1d) in CFA pain-related PVT engram neurons as a potential target for treating CDC. These findings identified novel CDC neuronal and molecular mechanisms in the PVT and provided insight into the complicated pain neuropathology under a comorbid state with depression and related drug development.

Iodine Adsorption-Desorption-Induced Structural Transformation and Improved Ag+ Turn-On Luminescent Sensing Performance of a Nonporous Eu(III) Metal-Organic Framework.

Posttreatment of pristine metal-organic frameworks (MOFs) with suitable vapor may be an effective way to regulate their structures and properties but has been less explored. Herein, we report an interesting example in which a crystalline nonporous Eu(III)-MOF was transferred to a porous amorphous MOF (aMOF) via iodine vapor adsorption-desorption posttreatment, and the resulting aMOF showed improved turn-on sensing properties with respect to Ag+ ions. The crystalline Eu-MOF, namely, Eu-IPDA, was assembled from Eu(III) and 4,4'-{4-[4-(1H-imidazol-1-yl)phenyl]pyridine-2,6-diyl}dibenzoic acid (H2IPDA) and exhibited a two-dimensional (2D) coordination network based on one-dimensional secondary building blocks. The close packing of the 2D networks gives rise to a three-dimensional supramolecular framework without any significant pores. Interestingly, the nonporous Eu-IPDA could absorb iodine molecules when Eu-IPDA crystals were placed in iodine vapor at 85 °C, and the adsorption capacity was 1.90 g/g, which is comparable to those of many MOFs with large BET surfaces. The adsorption of iodine is attributed to the strong interactions among the iodine molecule, the carboxy group, and the N-containing group and leads to the amorphization of the framework. After immersion of the iodine-loaded Eu-IPDA in EtOH, approximately 89.7% of the iodine was removed, resulting in a porous amorphous MOF, denoted as a-Eu-IPDA. In addition, the remaining iodine in the a-Eu-IPDA framework causes strong luminescent quenching in the fluorescence emission region of the Eu(III) center when compared with that in Eu-IPDA. The luminescence intensity of a-Eu-IPDA in water suspensions was significantly enhanced when Ag+ ions were added, with a detection limit of 4.76 × 10-6 M, which is 1000 times that of pristine Eu-IPDA. It also showed strong anti-interference ability over many common competitive metal ions and has the potential to sense Ag+ in natural water bodies and traditional Chinese medicine preparations. A mechanistic study showed that the interactions between Ag+ and the absorbed iodine, the carboxylate group, and the N atoms all contribute to the sensing performance of a-Eu-IPDA.

Full-length transcriptome characterization of Platycladus orientalis based on the PacBio platform.

As a unique and native conifer in China, Platycladus orientalis is widely used in soil erosion control, garden landscapes, timber, and traditional Chinese medicine. However, due to the lack of reference genome and transcriptome, it is limited to the further molecular mechanism research and gene function mining. To develop a full-length reference transcriptome, tissues from five different parts of P. orientalis and four cone developmental stages were sequenced and analyzed by single-molecule real-time (SMRT) sequencing through the PacBio platform in this study. Overall, 37,111 isoforms were detected by PacBio with an N50 length of 2,317 nt, an average length of 1,999 bp, and the GC content of 41.81%. Meanwhile, 36,120 coding sequences, 5,645 simple sequence repeats (SSRs), 1,201 non-coding RNAs (lncRNAs), and 182 alternative splicing (AS) events with five types were identified using the results obtained from the PacBio transcript isoforms. Furthermore, 1,659 transcription factors (TFs) were detected and belonged to 51 TF families. A total of 35,689 transcripts (96.17%) were annotated through the NCBI nr, KOG, Swiss-Prot and KEGG databases, and 385 transcript isoforms related to 8 types of hormones were identified incorporated into plant hormone signal transduction pathways. The assembly and revelation of the full-length transcriptome of P. orientalis offer a pioneering insight for future investigations into gene function and genetic breeding within Platycladus species.

Nontargeted metabolomics and enzyme inhibitory and antioxidant activities for chemical and biological characterization of jujube (Ziziphus jujuba) extracts.

The chemical and biologically active characterization of jujube samples (fruits, cores, and leaves) were carried out by the integrated nontargeted metabolomics and bioassay. Firstly, collision cross-section values of active compounds in jujubes were determined by ultrahigh-performance liquid chromatography coupled with ion mobility quadrupole time-of-flight mass spectrometry. Then, a multidimensional statistical analysis that contained principal component analysis, partial least squares-discriminant analysis and hierarchical clustering analysis was employed to effectively cluster different tissues and types of jujubes, making identification more scientific. Furthermore, angiotensin-converting enzyme (ACE) and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) were used to evaluate the quality of jujubes from a double activity dimension. The analytical results obtained by using ACE and DPPH to evaluate the quality of jujube were different from multivariate statistics, providing a reference for the application of jujube. Therefore, integrating chemical and biological perspectives to evaluate the quality of jujube provided a more comprehensive evaluation and effective reference for clinical needs.

Aggressive NK-cell Leukemia: A Case Report and Literature Review.

Objective: To improve the understanding of aggressive NK-cell leukemia (ANKL) and summarize the progress of its diagnosis and treatment. Methods: We retrospectively analyzed a case of a patient who was initially diagnosed with T-cell lymphoma (non-specific type) and later transformed into ANKL through examinations such as bone marrow smear, flow cytometry, Q-mNGS, and pathology. We described the patient's diagnostic and treatment journey and conducted a literature review. Results: The patient presented with concomitant hemophagocytic syndrome upon admission. After treatment with the HLH-94 regimen, the patient developed tumor lysis syndrome, leading to a sudden onset of ventricular tachycardia and respiratory and cardiac arrest on the third day of admission. Despite aggressive resuscitation efforts, the patient did not survive. Conclusions: ANKL is rare in the world, and the disease is aggressive, so it is necessary to diagnose early and intervene timely. Bone marrow smear, flow cytometer and Q-mNGS are helpful to identify tumors quickly and determine the direction of diagnosis and treatment. This disease is often accompanied by hemophagocytic syndrome. When the pathogenesis is not clear, it is recommended to treat it with hormone and gamma globulin first, and after clarification, chemotherapy containing L-asparaginase may be added; pay attention to supportive treatment and vigilance against oncolysis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be performed as soon as possible, and the application of targeted drugs may further improve the curative effect. In a word, ANKL needs more data statistics and analysis to guide clinical diagnosis and treatment.

A study on pharmaceutical text relationship extraction based on heterogeneous graph neural networks.

Effective information extraction of pharmaceutical texts is of great significance for clinical research. The ancient Chinese medicine text has streamlined sentences and complex semantic relationships, and the textual relationships may exist between heterogeneous entities. The current mainstream relationship extraction model does not take into account the associations between entities and relationships when extracting, resulting in insufficient semantic information to form an effective structured representation. In this paper, we propose a heterogeneous graph neural network relationship extraction model adapted to traditional Chinese medicine (TCM) text. First, the given sentence and predefined relationships are embedded by bidirectional encoder representation from transformers (BERT fine-tuned) word embedding as model input. Second, a heterogeneous graph network is constructed to associate words, phrases, and relationship nodes to obtain the hidden layer representation. Then, in the decoding stage, two-stage subject-object entity identification method is adopted, and the identifier adopts a binary classifier to locate the start and end positions of the TCM entities, identifying all the subject-object entities in the sentence, and finally forming the TCM entity relationship group. Through the experiments on the TCM relationship extraction dataset, the results show that the precision value of the heterogeneous graph neural network embedded with BERT is 86.99% and the F1 value reaches 87.40%, which is improved by 8.83% and 10.21% compared with the relationship extraction models CNN, Bert-CNN, and Graph LSTM.

[Effect of maxillary expansion combined with orofacial myofunctional therapy on the position of the tongue of children with mouth breathing].

Objective:This study aimed to investigate the change of the position of the tongue before and after combined treatment of maxillary expansion and orofacial myofunctional therapy in children with mouth-breathing and skeletal class Ⅱmalocclusion. Methods:A total of 30 children with skeletal class Ⅱ malocclusion and unobstructed upper airway were selected. The 30 children were divided into mouth-breathing group（n=15） and nasal-breathing group（n=15） and CBCT was taken. The images were measured by Invivo5 software. The measurement results of the tongue position of the two groups were analyzed by independent samples t-test. 15 mouth-breathing children with skeletal class Ⅱ malocclusion were selected for maxillary expansion and orofacial myofunctional therapy. CBCT was taken before and after treatment, the measurements were analyzed by paired sample t test with SPSS 27.0 software package. Results:The measurement of the tongue position of the mouth-breathing and nasal-breathing groups were compared, the differences were statistically significant（P<0.05）. The measurement of the tongue position showed significant difference after the combined treatment of maxillary expansion and orofacial myofunctional therapy in children with mouth-breathing and skeletal class Ⅱmalocclusion（P<0.05）. Conclusion:Skeletal class Ⅱ malocclusion children with mouth-breathing have low tongue posture. The combined treatment of maxillary expansion and orofacial myofunctional therapy can change the position of the tongue.

Network Pharmacology and Experimental Validation to Explore Mechanism of Tetrahydropalmatine on Acute Myocardial Ischemia.

OBJECTIVE: To explore the potential molecular mechanism of tetrahydropalmatine (THP) on acute myocardial ischemia (AMI). METHODS: First, the target genes of THP and AMI were collected from SymMap Database, Traditional Chinese Medicine Database and Analysis Platform, and Swiss Target Prediction, respectively. Then, the overlapping target genes between THP and AMI were evaluated for Grene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction network analysis. The binding affinity between the protein and THP was assessed by molecular docking. Finally, the protective effects of THP on AMI model and oxygen and glucose deprivation (OGD) model of H9C2 cardiomyocyte were explored and the expression levels of target genes were detected by RT-qPCR in vivo and in vitro. RESULTS: MMP9, PPARG, PTGS2, SLC6A4, ESR1, JAK2, GSK3B, NOS2 and AR were recognized as hub genes. The KEGG enrichment analysis results revealed that the potential target genes of THP were involved in the regulation of PPAR and hormone pathways. THP improved the cardiac function, as well as alleviated myocardial cell damage. Furthermore, THP significantly decreased the RNA expression levels of MMP9, PTGS2, SLC6A4, GSK3B and ESR1 (P<0.05, P<0.01) after AMI. In vitro, THP significantly increased H9C2 cardiomyocyte viability (P<0.05, P<0.01) and inhibited the RNA expression levels of PPARG, ESR1 and AR (P<0.05, P<0.01) in OGD model. CONCLUSIONS: THP could improve cardiac function and alleviate myocardial injury in AMI. The underlying mechanism may be inhibition of inflammation, the improvement of energy metabolism and the regulation of hormones.

[Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines(â ): classification of processing routes].

Oral solid dosage(OSD) occupies a key position in the market of Chinese patent medicines and new traditional Chinese medicines. Processing route is the foundation for the research and development of traditional Chinese medicine OSDs. On the basis of prescriptions and preparation methods of 1 308 traditional Chinese medicine OSDs recorded in the Chinese Pharmacopoeia, we summarized the patterns of processing routes of both modern dosage forms(tablets, granules, and capsules) and traditional dosage forms(pills and powder) and constructed a manufacturing classification system(MCS) based on the processing routes. Based on the MCS, statistical analyses were conducted respectively on medicinal materials, pharmaceutical excipients, extraction solvents in the pretreatment process, crushed medicinal materials, methods of concentration and purification, and methods of drying and granulation, aiming to uncover the process features. The results showed that each dosage form can be prepared via different routes with different processing methods of decoction pieces and raw materials for dosage preparation. The raw materials for dosage form preparation of traditional Chinese medicine OSDs included total extract, semi-extract, and total crushed powder, which accounted for different proportions. The raw materials for traditional dosage forms are mainly decoction pieces powder. Semi-extracts are the main raw materials for tablets and capsules, which account for 64.8% and 56.3%, respectively. Total extracts are the main raw materials for granules, with a proportion of 77.8%. Compared with tablets and capsules, traditional Chinese medicine granules with dissolubility requirements had a larger proportion of water extraction process, a higher proportion of refining process(34.7%), and a lower proportion of crushed medicinal mate-rials in semi-extract granules. There are four ways to add volatile oil to the modern dosage forms of traditional Chinese medicine. In addition, some new technologies and processes have been used in concentration, filtration, and granulation processes of traditional Chinese medicine OSDs, and the application of pharmaceutical excipients is diversified. The results of this study are expected to provide reference for the processing route design and upgrading of OSDs for new traditional Chinese medicines.

Disinhibition of Mesolimbic Dopamine Circuit by the Lateral Hypothalamus Regulates Pain Sensation.

Our recent study demonstrated the critical role of the mesolimbic dopamine (DA) circuit and its brain-derived neurotropic factor (BDNF) signaling in mediating neuropathic pain. The present study aims to investigate the functional role of GABAergic inputs from the lateral hypothalamus (LH) to the ventral tegmental area (VTA; LHGABA→VTA) in regulating the mesolimbic DA circuit and its BDNF signaling underlying physiological and pathologic pain. We demonstrated that optogenetic manipulation of the LHGABA→VTA projection bidirectionally regulated pain sensation in naive male mice. Optogenetic inhibition of this projection generated an analgesic effect in mice with pathologic pain induced by chronic constrictive injury (CCI) of the sciatic nerve and persistent inflammatory pain by complete Freund's adjuvant (CFA). Trans-synaptic viral tracing revealed a monosynaptic connection between LH GABAergic neurons and VTA GABAergic neurons. Functionally, in vivo calcium/neurotransmitter imaging showed an increased DA neuronal activity, decreased GABAergic neuronal activity in the VTA, and increased dopamine release in the NAc, in response to optogenetic activation of the LHGABA→VTA projection. Furthermore, repeated activation of the LHGABA→VTA projection was sufficient to increase the expression of mesolimbic BDNF protein, an effect seen in mice with neuropathic pain. Inhibition of this circuit induced a decrease in mesolimbic BDNF expression in CCI mice. Interestingly, the pain behaviors induced by activation of the LHGABA→VTA projection could be prevented by pretreatment with intra-NAc administration of ANA-12, a TrkB receptor antagonist. These results demonstrated that LHGABA→VTA projection regulated pain sensation by targeting local GABAergic interneurons to disinhibit the mesolimbic DA circuit and regulating accumbal BDNF release.SIGNIFICANCE STATEMENT The mesolimbic dopamine (DA) system and its brain-derived neurotropic factor (BDNF) signaling have been implicated in pain regulation, however, underlying mechanisms remain poorly understood. The lateral hypothalamus (LH) sends different afferent fibers into and strongly influences the function of mesolimbic DA system. Here, utilizing cell type- and projection-specific viral tracing, optogenetics, in vivo calcium and neurotransmitter imaging, our current study identified the LHGABA→VTA projection as a novel neural circuit for pain regulation, possibly by targeting the VTA GABA-ergic neurons to disinhibit mesolimbic pathway-specific DA release and BDNF signaling. This study provides a better understanding of the role of the LH and mesolimbic DA system in physiological and pathological pain.

Selenium and Bacillus proteolyticus SES synergistically enhanced ryegrass to remediate Cu-Cd-Cr contaminated soil.

Heavy metal compound contaminated soil is an ecological threat, and soil containing copper (Cu), cadmium (Cd) and chromium (Cr) simultaneously is widely distributed. The application of phytoremediation in heavy metal combined contamination is still limited. In this study, to explore whether and how exogenous selenium (Se) and Bacillus proteolyticus SES enhance the remediation of combined Cu-Cd-Cr contaminated soil by ryegrass, pot experiments were carried out. Se alone or in combination with B. proteolyticus SES treatment increased the removal rates of heavy metals in the rhizosphere soil by 17.38%-157.25% relative to the control, while Se + B. proteolyticus SES treatment played a greater role in improving the heavy metals tolerance of ryegrass and increasing the activity of soil acid phosphatase. Moreover, Se and B. proteolyticus SES favored the preferential recruitment of specific taxa with the capacity of plant growth promotion and heavy metals resistance to the rhizosphere. The rhizosphere soil of Se treatment was specifically enriched with Lysobacter, Rhodanobacter, Micrococcales, Paenarthrobacter, and Adhaeribacter, while from class Bacilli to genus Bacillus enriched extensively and specifically in the rhizosphere of B. proteolyticus SES + Se treatment. Furthermore, five functional beneficial rhizosphere microbes including: Microbacterium sp., Pseudomonas extremaustralis, Bacillus amyloliquefaciens, Priestia megaterium, and Bacillus subtilis were isolated from the two treatments with the best remediation effect and synthetic communities (SynComs) were constructed. SynComs inoculation experiment further demonstrated the role of specific beneficial microbes in regulating the bioavailability of heavy metals. Results revealed that Se supplementation efficiently facilitated the phytoextraction of combined Cu-Cd-Cr contaminated soil, and B. proteolyticus SES inoculation showed the synergistical enhancement effect in the presence of Se.

[Guideline for clinical comprehensive evaluation of Chinese patent medicine (2022 version)].

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.

Corticotropin-releasing factor neurones in the paraventricular nucleus of the hypothalamus modulate isoflurane anaesthesia and its responses to acute stress in mice.

BACKGROUND: Corticotropin-releasing factor (CRF) neurones in the paraventricular nucleus (PVN) of the hypothalamus (PVNCRF neurones) can promote wakefulness and are activated under anaesthesia. However, whether these neurones contribute to anaesthetic effects is unknown. METHODS: With a combination of chemogenetic and molecular approaches, we examined the roles of PVNCRF neurones in isoflurane anaesthesia in mice and further explored the underlying cellular and molecular mechanisms. RESULTS: PVN neurones exhibited increased Fos expression during isoflurane anaesthesia (mean [standard deviation], 218 [69.3] vs 21.3 [7.3]; P<0.001), and ∼75% were PVNCRF neurones. Chemogenetic inhibition of PVNCRF neurones facilitated emergence from isoflurane anaesthesia (11.7 [1.1] vs 13.9 [1.2] min; P=0.001), whereas chemogenetic activation of these neurones delayed emergence from isoflurane anaesthesia (16.9 [1.2] vs 13.9 [1.3] min; P=0.002). Isoflurane exposure increased CRF protein expression in PVN (4.0 [0.1] vs 2.2 [0.3], respectively; P<0.001). Knockdown of CRF in PVNCRF neurones mimicked the effects of chemogenetic inhibition of PVNCRF neurones in facilitating emergence (9.6 [1.1] vs 13.0 [1.4] min; P=0.003) and also abolished the effects of chemogenetic activation of PVNCRF neurones on delaying emergence from isoflurane anaesthesia (10.3 [1.3] vs 16.0 [2.6] min; P<0.001). Acute, but not chronic, stress delayed emergence from isoflurane anaesthesia (15.5 [1.5] vs 13.0 [1.4] min; P=0.004). This effect was reversed by chemogenetic inhibition of PVNCRF neurones (11.7 [1.6] vs 14.7 [1.4] min; P=0.001) or knockdown of CRF in PVNCRF neurones (12.3 [1.5] vs 15.3 [1.6] min; P=0.002). CONCLUSIONS: CRF neurones in the PVN of the hypothalamus neurones modulate isoflurane anaesthesia and acute stress effects on anaesthesia through CRF signalling.

Applications of Diacylglycerol Acyltransferase for Triacylglycerol Production in Mortierella alpina.

Triacylglycerol (TG) with high-value long-chain polyunsaturated fatty acids is beneficial to human health; consequently, there is an urgent need to broaden its sources due to the current growing demand. Mortierella alpina, one of the most representative oleaginous fungi, is the only certificated source of dietary arachidonic acid-rich oil supplied in infant formula. This study was conducted to improve TG production in M. alpina by homologous overexpression of diacylglycerol acyltransferase (DGAT) and linseed oil (LSO) supplementation. Our results showed that the homologous overexpression of MaDGAT1B and MaDGAT2A strengthened TG biosynthesis and significantly increased the TG content compared to the wild-type by 12.24% and 14.63%, respectively. The supplementation with an LSO concentration of 0.5 g/L elevated the TG content to 83.74% and total lipid yield to 4.26 ± 0.38 g/L in the M. alpina-MaDGAT2A overexpression strain. Our findings provide an effective strategy for enhancing TG production and highlight the role of DGAT in TG biosynthesis in M. alpina.

Transcription Factor YY1 Ameliorates Liver Ischemia-reperfusion Injury Through Modulating the miR-181a-5p/ESR1/ERBB2 Axis.

BACKGROUND: Liver ischemia/reperfusion injury (I/RI) is characterized by inflammatory actions. Understanding the mechanistic insights underpinning inflammation is critical to developing treatment strategies. In this study, we illustrated the mechanistic insights of transcription factor Yin-Yang 1 (YY1)-mediated microRNA (miR)-181a-5p/estrogen receptor alpha (ESR1)/epidermal growth factor receptor 2 (ERBB2) axis in liver I/RI. METHODS: First, we established liver I/RI models in mice and hypoxia-reperfusion (H/R) cell models in mouse hepatocytes (AML12). Subsequently, the expression of YY1, miR-181a-5p, and ESR1 was determined in the 2 models. I/RI mouse models were further injected with lentivirus carrying oe-YY1' and H/R-exposed AML12 cells were subjected to a series of inhibitors, mimics, and shRNAs to validate the mechanisms of YY1 in controlling miR-181a-5p and ESR1 in liver I/RI. RESULTS: Upregulated expression of miR-181a-5p and downregulated expression of YY1 were identified in the liver tissues of liver I/RI mice and H/R-exposed hepatocytes. Moreover, overexpression of YY1 inhibited the miR-181a-5p expression and thus repressed the H/R-induced hepatocyte apoptosis and inflammation. ESR1 was further validated as a target gene of miR-181a-5p and could be negatively regulated by miR-181a-5p. miR-181a-5p inhibition elevated ESR1 expression, which consequently enhanced the ERBB2 expression and reduced H/R-induced hepatocyte apoptosis and inflammation. CONCLUSIONS: Overall, these findings highlighted that YY1 repressed the miR-181a-5p expression and stimulated ESR1-mediated activation of ERBB2, thereby ameliorating liver I/RI. This study provides insight into the development of novel targets for liver I/RI.

In situ assembled titanium carbide-based heterojunctions for the synergistic enhancement of NIR-II photothermal/photodynamic therapy against breast cancer.

The combined use of photothermal therapy (PTT) and photodynamic therapy (PDT) could circumvent the drawbacks of each individual therapeutic strategy, resulting in an enhanced antitumor effect. However, the lack of highly effective photo-agents that are irradiation-safe in the biologically transparent window hinder the advancement of phototherapy clinically. Hence, in this study, a charge separation engineering strategy was adopted to fabricate a nanoplatform with heterojunctions, namely, in situ TiO2-loaded MXene (Ti3C2/TiO2 heterojunctions). This nanoplatform exhibited reduced bandgap (1.68 eV), enhanced NIR-II photothermal conversion efficiency (44.98%), and extended absorption edge compared to pristine TiO2 for enhanced photodynamic effect. More importantly, the proliferation of tumor cells could be efficiently inhibited at a 5 mm chicken breast depth after 1064 nm laser irradiation, and the intracellular ROS production significantly increased under 660 nm or even 1064 nm laser irradiation with heterojunctions (HJs) compared with that of TiO2. Moreover, the in vivo data further confirmed that the as-prepared heterojunctions could efficiently eradicate tumors efficiently via improved photothermal effect with NIR-II laser irradiation and upregulated ROS production. Collectively, the reported HJs strategy provides an opportunity for the success of combinational PTT and PDT therapy in tumor treatment.

DosR Regulates the Transcription of the Arginine Biosynthesis Gene Cluster by Binding to the Regulatory Sequences in Mycobacterium bovis Bacille Calmette-Guerin.

l-Arginine serves as a carbon and nitrogen source and is critical for Mycobacterium tuberculosis (Mtb) survival in the host. Generally, ArgR acts as a repressor regulating arginine biosynthesis by binding to the promoter of the argCJBDFGH gene cluster. In this study, we report that the dormancy regulator DosR is a novel arginine regulator binding to the promoter region of argC (rv1652), which regulates arginine synthesis. Phosphorylation modification promoted DosR binding to a region upstream of the promoter. Cofactors, including arginine and metal ions, had an inhibitory effect on this association. Furthermore, DosR regulatory function relies on the interaction of the 167, 181, 182, and 197 amino acid residues with an inverse complementary sequence. Arginine also binds to DosR and directly affects its DNA-binding ability. Together, the results demonstrate that DosR acts as a novel transcriptional regulator of arginine synthesis in Mycobacterium bovis bacille Calmette-Guerin.

Implementation and challenges to preventing the re-establishment of malaria in China in the COVID-19 era.

BACKGROUND: The rapid emergence and global spread of COVID-19 have caused substantial global disruptions that have impacted malaria programs worldwide. Innovative strategies to enable countries aiming to eliminate malaria as well as those that are already certified as malaria-free, are needed to address malaria importation in the context of the COVID-19 pandemic. China was certified as malaria-free in 2021 and now aims to prevent the malaria re-establishment. Nonpharmaceutical interventions such as entry screening, quarantining, and health education for individuals returning from international travel during the COVID-19 pandemic present both opportunities and challenges to the management of imported malaria. This study aimed to describe and analyze the operational challenges associated with an integrated surveillance and case management program in which malaria re-establishment prevention measures were incorporated into the COVID-19 program in China. METHODS: After the integration of malaria re-establishment prevention activities into the COVID-19 program for 10 months in Jiangsu Province, China, a focus-group discussion of public health workers working on preventing malaria re-establishment and controlling COVID-19 was held in June 2021, aiming to explore the operational challenges and lessons learned from the integrated approach. RESULTS: From 01 August 2020 to 31 May 2021, 8,947 overseas travelers with Yangzhou as the final destination underwent 14-day managed quarantine and 14-day home isolation. Of these travelers, 5,562 were from malaria-endemic regions. A total of 26,026 education booklets and materials were distributed to expand malaria-related knowledge. Twenty-two patients with unknown fever were screened for malaria with rapid diagnostic tests, and one patient was confirmed to have imported malaria. The challenges associated with the implementation of the integrated malaria surveillance and case management program include neglect of malaria due to COVID-19, lack of a standard operating procedure for malaria screening, mobility of public health providers, and difficulties in respecting the timeline of the "1-3-7" surveillance strategy. CONCLUSIONS: China's experience highlights the feasibility of integrated case surveillance and management of existing infectious diseases and new emerging infections. It also demonstrates the importance of a sound public health infrastructure with adequate, trained field staff for screening, testing, contact tracing, and providing health education, all of which are crucial for the success of both malaria re-establishment prevention program and the effective control of COVID-19.

Optimization of mechanically assisted coamorphous dispersion extraction of hydrophobic compounds from plant tea (Citri Reticulatae Pericarpium) using water.

This study aimed to establish a novel mechanically assisted coamorphous dispersion extraction (MADE) method for the extraction of hydrophobic compounds (hesperidin, nobiletin and tangeretin) from Citri Reticulatae Pericarpium using water. The surface morphology, particle size distributions, phase states and functional groups of the coground product surface were characterized by Scanning Electron Microscopy, X-ray diffraction and Fourier transform infrared spectroscopy. The parameters affecting the efficiency of extraction method were optimized by single-factor experiments and response surface methodology. The method showed good linear relationships in the range of 1-500 µg/mL with correlation coefficients (R2) ≥ 0.9990, low limits of detection ranging from 3.0 to 28.3 ng/mL, and acceptable recoveries ranging from 87.0 to 91.0%. Therefore, the proposed MADE method is a promising, efficient and organic solvent-free method for the extraction of hydrophobic compounds from plant tea.