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Graphene hydrogel (GH) and aerogel (GA) have great application potential as highly effective adsorbents, but the accessibility of their adsorption sites have not yet been identified, restricting our understanding on the adsorption mechanisms and manufacturing. This study comparatively studied the adsorption characteristics of bisphenol A (BPA) and naphthalene (NAP) on GH and GA, focussing on the accessibility of the adsorption sites. The adsorption of BPA on GA was much lower but faster than that on GH. NAP adsorption on GA was very close to that on GH but faster than that on the latter. Considering that NAP is volatilisable, we speculate that some unwetted sites in the air-enclosed pores are available to it, but not to BPA. We applied ultrasonic and vacuum treatments to remove the air in GA pores, which was verified using a CO2 replacement experiment. BPA adsorption was greatly enhanced but slowed, while that of NAP was not enhanced. This phenomenon suggested that some inner pores became accessible in the aqueous phase after air removal from pores. The enhanced accessibility of air-enclosed pores was verified by the increased relaxation rate of surface-bounded water on GA, based on a 1H NMR relaxation analysis. This study highlights that the accessibility of adsorption site plays a crucial role for the adsorption properties of carbon-based aerogel. The volatile chemicals may be quickly adsorbed in the air-enclosed pores, which be useful for immobilizing volatile contaminants.

Background: Afatinib is an irreversible epidermal growth factor receptor tyrosine kinase inhibitor, and it plays a role in hepatocellular carcinoma (LIHC). This study aimed to screen a key gene associated with afatinib and identify its potential candidate drugs.Methods: We screened afatinib-associated differential expressed genes based on transcriptomic data of LIHC patients from The Cancer Genome Atlas, Gene Expression Omnibus, and the Hepatocellular Carcinoma Database (HCCDB). By using the Genomics of Drug Sensitivity in Cancer 2 database, we determined candidate genes using analysis of the correlation between differential genes and half-maximal inhibitory concentration. Survival analysis of candidate genes was performed in the TCGA dataset and validated in HCCDB18 and GSE14520 datasets. Immune characteristic analysis identified a key gene, and we found potential candidate drugs using CellMiner. We also evaluated the correlation between the expression of ADH1B and its methylation level. Furthermore, Western blot analysis was performed to validate the expression of ADH1B in normal hepatocytes LO2 and LIHC cell line HepG2.Results: We screened eight potential candidate genes (ASPM, CDK4, PTMA, TAT, ADH1B, ANXA10, OGDHL, and PON1) associated with afatinib. Patients with higher ASPM, CDK4, PTMA, and TAT exhibited poor prognosis, while those with lower ADH1B, ANXA10, OGDHL, and PON1 had unfavorable prognosis. Next, ADH1B was identified as a key gene negatively correlated with the immune score. The expression of ADH1B was distinctly downregulated in tumor tissues of pan-cancer. The expression of ADH1B was negatively correlated with ADH1B methylation. Small-molecule drugs panobinostat, oxaliplatin, ixabepilone, and seliciclib were significantly associated with ADH1B. The protein level of ADH1B was significantly downregulated in HepG2 cells compared with LO2 cells.Conclusion: Our study provides ADH1B as a key afatinib-related gene, which is associated with the immune microenvironment and can be used to predict the prognosis of LIHC. It is also a potential target of candidate drugs, sharing a promising approach to the development of novel drugs for the treatment of LIHC.

Trichosporeae is the largest and most taxonomically difficult tribe of Gesneriaceae due to its diverse morphology. Previous studies have not clarified the phylogenetic relationships within this tribe on several DNA markers, including the generic relationships within subtribes. Recently, plastid phylogenomics have been successfully employed to resolve the phylogenetic relationships at different taxonomic levels. In this study, plastid phylogenomics were used to explore the relationships within Trichosporeae. Eleven plastomes of Hemiboea were newly reported. Comparative analyses, phylogeny and morphological character evolution within Trichosporeae were conducted on 79 species representing seven subtribes. The Hemiboea plastomes range from 152,742 bp to 153,695 bp in length. Within Trichosporeae, the sampled plastomes range from 152,196 bp to 156,614 bp and GC content from 37.2% to 37.8%. A total of 121–133 genes were annotated in each species, including 80–91 protein-coding genes, 34–37 tRNA genes, and 8 rRNA genes. The contraction and expansion of IR borders were not detected, and gene rearrangements and inversions did not occur. The 13 hypervariable regions were proposed as the potential molecular markers for species identification. A total of 24,299 SNPs and 3,378 indels were inferred, and most of the SNPs were functionally missense and silent variations. There were 1968 SSRs, 2055 tandem repeats and 2802 dispersed repeats. The RSCU and ENC values indicated that the codon usage pattern was conserved in Trichosporeae. Both the phylogenetic frameworks based on the whole plastome and 80 CDSs were basically concordant. The sister relationships between Loxocarpinae and Didymocarpinae were confirmed, and Oreocharis was a sister group of Hemiboea with high support. The morphological characters showed a complex evolutionary pattern of Trichosporeae. Our findings may contribute to future research on genetic diversity, morphological evolutionary patterns, and conservation of the tribe Trichosporeae.

Summary: N6-adenine DNA methylation (6mA), a rediscovered epigenetic mark in eukaryotic organisms, diversifies in abundance, distribution, and function across species, necessitating its study in more taxa. Paramecium bursaria is a typical model organism with endosymbiotic algae of the species Chlorella variabilis. This consortium therefore serves as a valuable system to investigate the functional role of 6mA in endosymbiosis, as well as the evolutionary importance of 6mA among eukaryotes. In this study, we report the first genome-wide, base pair-resolution map of 6mA in P. bursaria and identify its methyltransferase PbAMT1. Functionally, 6mA exhibits a bimodal distribution at the 5′ end of RNA polymerase II-transcribed genes and possibly participates in transcription by facilitating alternative splicing. Evolutionarily, 6mA co-evolves with gene age and likely serves as a reverse mark of endosymbiosis-related genes. Our results offer new insights for the functional diversification of 6mA in eukaryotes as an important epigenetic mark.

People generally spend most of their time indoors, making indoor air quality be of great significance to human health. Large spatiotemporal heterogeneity of indoor air pollution can be hardly captured by conventional filter-based monitoring but real-time monitoring. Real-time monitoring is conducive to change air assessment mode from static and sparse analysis to dynamic and massive analysis, and has made remarkable strides in indoor air evaluation. In this review, the state of art, strengths, challenges, and further development of real-time sensors used in indoor air evaluation are focused on. Researches using real-time sensors for indoor air evaluation have increased rapidly since 2018, and are mainly conducted in China and the USA, with the most frequently investigated air pollutants of PM2.5. In addition to high spatiotemporal resolution, real-time sensors for indoor air evaluation have prominent advantages in 3-dimensional monitoring, pollution peak and source identification, and short-term health effect evaluation. Huge amounts of data from real-time sensors also facilitate the modeling and prediction of indoor air pollution. However, challenges still remain in extensive deployment of real-time sensors indoors, including the selection, performance, stability, as well as calibration of sensors. In future, sensors with high performance, long-term stability, low price, and low energy consumption are welcomed. Furthermore, more target air pollutants are also expected to be detected simultaneously by real-time sensors in indoor air monitoring.

Oil is one of the main components in maize kernels. Increasing the total oil content (TOC) is favorable to optimize feeding requirement by improving maize quality. To better understand the genetic basis of TOC, quantitative trait loci (QTL) in four double haploid (DH) populations were explored. TOC exhibited continuously and approximately normal distribution in the four populations. The moderate to high broad-sense heritability (67.00-86.60%) indicated that the majority of TOC variations are controlled by genetic factors. A total of 16 QTLs were identified across all chromosomes in a range of 3.49-30.84% in term of phenotypic variation explained. Among them, six QTLs were identified as the major QTLs that explained phenotypic variation larger than 10%. Especially, qOC-1-3 and qOC-2-3 on chromosome 9 were recognized as the largest effect QTLs with 30.84% and 21.74% of phenotypic variance, respectively. Seventeen well-known genes involved in fatty acid metabolic pathway located within QTL intervals. These QTLs will enhance our understanding of the genetic basis of TOC in maize and offer prospective routes to clone candidate genes regulating TOC for breeding program to cultivate maize varieties with the better grain quality.

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of kidney transplantation, and whole-body 18F- FDG PET/CT imaging plays a key role in patients with PTLD. This article reports three cases of 18F-FDG PET/CT manifestations of gastric, prostate, and pulmonary lymphomas after kidney transplantation, all of which showed local lesions without involvement of adjacent or distant lymph nodes and lymphoid node organs. All patients were treated with a reduced dose of R–CHOP and were generally in a good condition after discharge. Early diagnosis and reasonable treatment are key factors in achieving a better prognosis in patients with PTLD, and whole-body 18F-FDG PET/CT imaging plays an important role in the diagnosis and monitoring of PTLD.

Polycystic ovarian syndrome (PCOS) is associated with hyperandrogenemia and ovarian antral follicle growth arrest. We have previously demonstrated that androgen-induced exosomal release of miR-379-5p (miR379) from preantral follicle granulosa cells increases the proliferation of target cells via phosphoinositide-dependent kinase 1 (PDK1) upregulation. Androgen also increases inflammatory M1 macrophage abundance, but reduces anti-inflammatory M2 polarization in rat antral and preovulatory follicles. However, the role of small extracellular vesicles (sEVs; also known as exosomes) secretion in determining the cellular content and function of miRNAs in exosome-receiving cells is largely unknown. Our objectives were to determine: 1) the regulatory role of granulosa cells (GC)-derived exosomal miR379 on macrophage polarization and ovarian inflammation; 2) whether miR379-induced M1 polarization regulates GC proliferation; and 3) if this regulated process is follicular stage-specific. Compared with non-PCOS subjects, PCOS subjects had a higher M1/M2 ratio, supporting the concept that PCOS is an inflammatory condition. Ovarian overexpression of miR379 increased the number of M1 macrophages and the M1/M2 ratio in preantral follicles specifically. Transfection of macrophages with a miR379 mimic reduced the cellular content of PDK1 and induced M0→M1 polarization; whereas its inhibitor polarized M0→M2. Conditioned media from macrophages transfected with miR379 mimic and follicular fluid from PCOS subjects had higher galectin-3 content, a pro-inflammatory cytokine which specifically suppresses human antral follicle GC proliferation. These results indicate that miR379 inhibits M2 macrophage polarization, a condition which suppresses GC proliferation in a follicle stage-dependent manner, as exhibited in PCOS.

Abstract Auricular arteriovenous malformations (AVMs) can cause a variety of symptoms that seriously impact the patient's appearance, life, and mental well‐being. Surgery is the primary management method for auricular AVMs, but there is no consensus on how to surgically manage auricular AVMs. In this article, we document a comprehensive review of the characteristics, classification, and surgical interventions to treat auricular AVMs.

Abstract The tissue expansion technique is the most suitable procedure for Chinese patients with microtia. However, it is difficult to determine whether the expanded flap is sufficient, and there are no clear or objective guidelines for determining the volume of the expander for different sizes of auricles. One hundred patients with unilateral microtia who visited our department in 2021 were randomly selected for auricular data collection using 3D scanning. The auricle length, width, projection, perimeter, and surface area were measured. Eight different volumes of expanders underwent CT and the surface areas of these expanders were measured. The surface areas of the auricles and expanders were compared and the correlation between them was explored. The average auricle parameters were calculated. The scatter plot showed a linear relationship between auricle length and auricle surface area (R2 = 0.9913), which demonstrated that the auricle area was approximately equal to the auricle length multiplied by 76.921. Additionally, the surface area of the expanders was measured and made into a table for selection against the surface area of the auricles. Using our equation, the auricle surface could be estimated by simply measuring the non-defective auricle length; therefore, the suitable volume of the expander could be determined.

Abstract Background The de-escalation treatment in patients with low-risk HER2-positive early breast cancer (eBC) is an attractive strategy to avoid unnecessary treatment and improve the quality of life of patients. Pyrotinib, a novel irreversible pan-HER2 tyrosine kinase inhibitor (TKI), has shown efficacy in patients with advanced HER2-positive breast cancer. Meanwhile, nanoparticle albumin-bound (nab)-paclitaxel reveals survival benefit over solvent-based paclitaxel and eliminates the toxicities associated with the solvent. However, the efficacy and safety of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for low-risk HER2 + eBC patients have not been evaluated. Methods This is a multicenter, open-label, single-arm phase II study. A sample size of 261 patients with tumor ≤ 3 cm, lymph node-negative (N0) or micrometastatic (N1mi), HER2 + breast cancer will be recruited. Eligible patients will receive nab-paclitaxel 260 mg/m2 once every 3 weeks for 12 weeks and pyrotinib 400 mg once daily for one year. The primary endpoint is invasive disease-free survival. A sub-study will be conducted to investigate different prophylactic strategies for diarrhea, which is the most common adverse event of pan-HER TKIs. One hundred and twenty patients from the main study will be randomly (1:1) allocated to receive loperamide either during the first cycle (4 mg tid on days 1–7, then 4 mg bid on days 8–21) or the first 2 cycles (4 mg tid on days 1–7, then 4 mg bid on days 8–42). The primary endpoint of the sub-study is the incidence of grade ≥ 3 diarrhea. Discussion This is the first prospective study of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for patients with low-risk HER2-positive eBC. It would probably provide robust evidence for de-escalating strategy of HER2-positive eBC and appropriate management for pyrotinib-related diarrhea. Trial registration ClinicalTrials.gov Identifier: NCT04659499 . Registered on December 9, 2020.

Refractory skin defects such as pressure ulcers, diabetic ulcers, and vascular ulcers represent a challenge for clinicians and researchers in many aspects. The treatment strategies for wound healing have high cost and limited efficacy. To ease the financial and psychological burden on patients, a more effective therapeutic approach is needed to address the chronic wound. MSC-derived exosomes (MSC-exosomes), the main bioactive extracellular vesicles of the paracrine effect of MSCs, have been proposed as a new potential cell-free approach for wound healing and skin regeneration. The benefits of MSC-exosomes include their ability to promote angiogenesis and cell proliferation, increase collagen production, regulate inflammation, and finally improve tissue regenerative capacity. However, poor targeting and easy removability of MSC-exosomes from the wound are major obstacles to their use in clinical therapy. Thus, the concept of bioengineering technology has been introduced to modify exosomes, enabling higher concentrations and construction of particles of greater stability with specific therapeutic capability. The use of biomaterials to load MSC-exosomes may be a promising strategy to concentrate dose, create the desired therapeutic efficacy, and maintain a sustained release effect. The beneficial role of MSC-exosomes in wound healing is been widely accepted; however, the potential of bioengineering-modified MSC-exosomes remains unclear. In this review, we attempt to summarize the therapeutic applications of modified MSC-exosomes in wound healing and skin regeneration. The challenges and prospects of bioengineered MSC-exosomes are also discussed.

Schizophrenia is a group of severe mental disorders. MiR-25-3p was shown to be involved in various neuropsychiatric diseases and can regulate SIK1 and TWIST1. The CRTC2/CREB1 and PI3K/Akt/GSK3β signaling pathways are downstream pathways of SIK1 and TWIST1, respectively. This study investigated whether miR-25-3p-mediated SIK1/CRTC2/CREB1 and TWIST1/PI3K/Akt/GSK3β signaling pathways are present in an animal model relevant to schizophrenia. A schizophrenic rat model was established by using sub-chronic MK-801 administration. An RNA-seq test was performed to examine the differentially expressed genes (DEGs) in the rat prefrontal cortex (PFC). The mRNA levels of miR-25-3p, SIK1, and TWIST in the PFC and caudate putamen (CPu) were assessed by qRT-PCR. Phosphorylation of the SIK1/CRTC2/CREB1 and TWIST1/PI3K/Akt/GSK3β pathways in the two brain regions was examined by Western blots. The RNA-seq data revealed down-regulated miR-25-3p expression and up-regulated SIK1 and TWIST1 mRNA expression induced by MK-801. Additionally, SIK1 and TWIST1 were shown to be possible downstream responders of miR-25-3p in previous studies. qRT-PCR confirmed the changes of miR-25-3p, SIK1, and TWIST1 induced by MK-801 in both brain regions, which, however, was reversed by risperidone. Furthermore, the phosphorylation of the SIK1/CRTC2/CREB1 pathway was repressed by MK-801, whereas the phosphorylation of the TWIST1/PI3K/Akt/GSK3β pathway was increased by MK-801 in either of the two brain regions. Moreover, the altered phosphorylation of these two signaling pathways induced by MK-801 can be restored by risperidone. In conclusion, this study suggests that altered SIK1/CRTC2/CREB1 and TWIST1/PI3K/Akt/GSK3β signaling pathways mediated by miR-25-3p is very likely to be associated with schizophrenia, revealing potential targets for the treatment and clinical diagnosis of schizophrenia.

Abstract Forming metallurgical phases has a critical impact on the performance of dissimilar materials joints. Here, we shed light on the forming mechanism of equilibrium and non-equilibrium intermetallic compounds (IMCs) in dissimilar aluminum/steel joints with respect to processing history (e.g., the pressure and temperature profiles) and chemical composition, where the knowledge of free energy and atomic diffusion in the Al–Fe system was taken from first-principles phonon calculations and data available in the literature. We found that the metastable and ductile (judged by the presently predicted elastic constants) Al6Fe is a pressure (P) favored IMC observed in processes involving high pressures. The MoSi2-type Al2Fe is brittle and a strong P-favored IMC observed at high pressures. The stable, brittle η-Al5Fe2 is the most observed IMC (followed by θ-Al13Fe4) in almost all processes, such as fusion/solid-state welding and additive manufacturing (AM), since η-Al5Fe2 is temperature-favored, possessing high thermodynamic driving force of formation and the fastest atomic diffusivity among all Al–Fe IMCs. Notably, the ductile AlFe3, the less ductile AlFe, and most of the other IMCs can be formed during AM, making AM a superior process to achieve desired IMCs in dissimilar materials. In addition, the unknown configurations of Al2Fe and Al5Fe2 were also examined by machine learning based datamining together with first-principles verifications and structure predictions. All the IMCs that are not P-favored can be identified using the conventional equilibrium phase diagram and the Scheil-Gulliver non-equilibrium simulations.

Tongue diagnosis is a unique aspect of traditional Chinese medicine for diagnosing diseases before determining proper means of treatment, but it also has the disadvantage of relying on the subjective experience of medical practitioners and lack objective basis. The purpose of this article is to elucidate tongue-coating microbiota and metabolic differences in primary liver cancer (PLC) patients with thick or greasy tongue coatings. Tongue-coating samples were analyzed in 60 PLC patients (30 PLC with thick or greasy tongue-coating patients and 30 PLC with tongue-coating neither thick nor greasy) and 25 healthy controls (HC) using 16S rRNA gene sequencing technology. As compared to healthy individuals, tongue coatings of patients with PLC had elevated levels of Firmicutes and Actinobacteria. The abundance of Fusobacteria, SR1_Absconditabacteria_, and Spirochaete were higher in tongue coatings of healthy controls compared to samples in patients with PLC. In addition to site-specific differences, higher abundances of Fusobacteria and Actinobacteria were observed in thick or greasy tongue-coating patients as compared to non-thick and greasy tongue-coating patients. The inferred metagenomic pathways enriched in the PLC tongue-coating patients were mainly those involved in replication, recombination, and repair of protein. We also identify a tongue-coating microbiome signature to discriminate HC and PLC, including 15 variables on genus level. The prediction performance of the signature showed well in the training and validation cohorts. This research illustrates specific clinical features and bacterial structures in PLC patients with different tongue coatings, which facilitates understanding of the traditional tongue diagnosis.

BackgroundCyclin-dependent kinase 4/6 inhibitor (CDK4/6i) has become the commonest first-line treatment of hormonal receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer (MBC). However, therapy is quite individualized after progression of disease (PD) when CDK4/6i fails. Estrogen receptor (ER) status of metastatic lesions of bone, lung or liver might be different from the primary tumor and biopsy of metastatic lesions was invasive and not always available. Prediction of treatment response after PD of CDK4/6i remains unsolved. 18F-fluoroestradiol (FES) PET/CT could non-invasively reveal ER expression both in primary and metastatic breast cancer and recognize heterogeneity of ER status.Case presentationA 70-year-old woman with Parkinson’s disease, osteoporosis and cardiovascular co-morbidity was diagnosed with HR+/HER2- breast cancer (pT2N2M0, stage IIIa). Three years later, she developed metastases in right lung and pleura with pleural effusion and received palbociclib + letrozole. After 8 months the disease progressed, and 18F-FES PET/CT revealed multiple ER-positive pleural lesions and ER-negative pulmonary nodules after PD and the progression-free survival (PFS) of first-line CDK4/6i was 8 months. Since most of the metastatic lesions were ER-positive, abemaciclib + fulvestrant were chosen as the second-line CDK4/6i treatment and the PFS was 15 months. Another 18F-FES PET/CT showed a new ER-positive pleural mass with multiple ER-negative pulmonary nodules. Since 18F-FES PET/CT revealed that the dominant lesions were still ER-positive, dalpiciclib + exemestane + fulvestrant were prescribed as the third-line CDK4/6i treatment. Currently the patient’s disease had been stable for 2 months.ConclusionThis case demonstrated that 18F-FES PET/CT could show ER heterogeneity non-invasively and reveal the treatment responses a predictive imaging tool of serial second- and third-line of CDK4/6i treatments when first-line CDK4/6i failed in HR+/HER2- MBC. So long as the dominant or newly-developed metastatic lesion was ER-positive on 18F-FES PET after first-line CDK4/6i, the patient might show certain therapeutic response towards endocrine-based treatment including second- and third-line of CDK4/6i, and thus increased the time to chemotherapy (TTC).

Inhalation exposure to polycyclic aromatic hydrocarbons (PAHs) from indoor solid fuel combustion poses a high health risk, and PAHs bound to particles with smaller sizes (e.g., PM1.0, aerodynamic diameter ≤ 1.0 µm) should be of particular concern since they can penetrate deep into pulmonary alveoli. However, PAHs bound to PM1.0 was less studied compared with PAHs in total suspended particles or PM2.5. In this study, multiple provincial field measurements were conducted to investigate 28 PAHs bound to PM1.0 in rural Chinese homes. Daily averaged PM1.0-PAH28 concentrations ranged from 27 ng/m3 to 3795 ng/m3 (median: 233 ng/m3) and from 10 ng/m3 to 2978 ng/m3 (median: 87 ng/m3) in indoor and outdoor air, respectively. Higher concentrations were found in northern China in winter due to increased solid fuels consumption for space heating. The ambient pollution was lower during the non-heating season in Eastern China, where clean energy was preferred. Highly toxic congeners were more abundant in indoor air compared with outdoor air. The results of source apportionment revealed that solid fuel combustion was the primary contributor to rural household PM1.0-PAHs, but other sources such as vehicles cannot be overlooked. The transition to cleaner energy can reduce the indoor PM1.0-PAH28 and BaPeq-28 concentrations by 87% and 98%, respectively, and more efficient reduction was observed for highly toxic congeners. The estimated Incremental Lifetime Cancer Risk (ILCR) based on PM1.0-PAH28 ranged from 4.6 × 10−5 to 3.4 × 10−2, far exceeding the acceptable level of 10−6. Over 60% of the ILCR could be attributed to inhalation exposure during childhood and adolescence.

Introduction: Longxuetongluo Capsule (LTC) is wildly applied to treat ischemic stroke in clinical practice in China. However, the pharmacological mechanism of LTC on ischemic stroke is still unstated. Objective: Our research was designed to study the protective effect of LTC against cerebral ischemia–reperfusion (I/R) injury and reveal the underlying mechanism both in vivo and in vitro. Methods: PC12 cells treated with glucose deprivation/reperfusion (OGD/R) were used to simulate in vitro ischemia/reperfusion (I/R) injury. The cell viability, apoptosis rate, and protein expressions of PC12 cells were evaluated. In vivo validation of the protective effect of LTC was carried out by middle cerebral artery occlusion (MCAO)/reperfusion treatment, and the underlying mechanism of its anti-apoptosis ability was further revealed by immunohistochemistry staining and Western blotting. Results: In the current study, we observed that LTC effectively inhibited oxygen-glucose deprivation/reperfusion (OGD/R) induced apoptosis of PC12 cells through suppressing the cleavage of poly ADP-ribose polymerase (PARP), caspase-3, and caspase-9. Further investigation revealed that OGD/R insult remarkably triggered the endoplasmic reticulum stress responses (ER stress) to induce PC12 cell apoptosis. LTC treatment alleviated OGD/R induced ER stress by inhibiting the activation of protein kinase RNA (PKR)-like ER kinase (PERK)/eukaryotic translation initiation factor 2 (eIF2α) and inositol requiring enzyme 1 (IRE1)/tumor necrosis factor receptor-associated factor 2 (TRAF2) pathways. Additionally, LTC also restrained the OGD/R-induced PC12 cell apoptosis by reversing the activated mitogen-activated protein kinase (MAPK) through IRE1/TRAF2 pathway. Animal studies demonstrated LTC significantly restricted the infarct region induced by middle cerebral artery occlusion (MCAO)/reperfusion, the activation of ER stress and apoptosis of neuronal cells had also been suppressed by LTC in the penumbra region. Conclusion: LTC protects the cerebral neuronal cell against ischemia/reperfusion injury through ER stress and MAPK-mediated mechanisms.

Abstract This study aimed to compare the therapeutic effects of biplane skin dilator implantation with those of conventional skin dilator implantation in auricular reconstruction. A total of 137 patients with microtia who met the inclusion criteria from January 2020 to April 2021 were retrospectively selected. Sixty-three patients comprised the control group and were implanted with a skin expander using the conventional method. Seventy-four patients comprised the experimental group and were implanted with a skin expander using the biplane method. Non-parametric tests were used to compare the down-moving distance of the skin dilator between the experimental group and the control group. There was a statistically significant difference in the down-moving distance of the skin dilator between the experimental group and the control group (P 0.05). Moreover, there was no significant difference in the satisfaction rate of patients and their families between the experimental group and the control group (P > 0.05). In this study, the treatment effect of biplane skin dilator implantation was better than that of conventional skin dilator implantation.

Five new species (Gastrochilus yei, Gastrochilus minimus, Luisia simaoensis, Taeniophyllum xizangense, Tuberolabium subulatum) and two newly recorded species (Cleisostoma tricornutum, Luisia inconspicua) of Vandeae (Orchidaceae) from China are described and illustrated. Gastrochilus yei is similar to G. affinis and G. nepalensis, but differs from them by having an epichile not lobed, the apex of the hypochile not bilobed, and a tine on the apex of the leaf. Gastrochilus minimus is similar to G. acinacifolius, but can be distinguished from the latter by having a flabellate epichile that is densely hirsute on the adaxial surface and an inconspicuous central cushion; in addition, the hypochile of G. minimus has a keel that extends to the apex of the epichile. Taeniophyllum xizangense is similar to T. stella and T. radiatum, but it is distinguished from them by having much bigger flowers, inflorescences densely covered with short-bristly hairs, papillae on the external surface of sepals, and bigger triangular-ovate viscidium. Luisia simaoensis is similar to L. magniflora and L. ramosii, but can be easily distinguished from them by having lateral sepals longer than dorsal sepals and petals, lip with irregular and waved margins, and lip with bilobed apex. Luisia inconspicua is moved from Gastrochilus to Luisia based on phylogenetic analyses of plastid matK sequence data. Tuberolabium subulatum is similar to T. carnosum, but it can be easily distinguished from the latter by having an inflorescence much shorter than the leaves, yellow sepals and petals, and many small papillae outside the lip lobes.

Background The chest wall deformity is a well-known complication following costal cartilage harvest with the biomechanical factor considered to be a cause of this donor-site morbidity. Kawanabe-Nagata method is a widely-accepted approach to prevent the deformity. However, knowledge about the biomechanical properties of regenerated costal cartilage is limited, and the value of reimplantation of autologous costal cartilage blocks is not clear. Methods The fifth costal cartilage on both sides of six male, 8 weeks of age, New Zealand white rabbits were harvested with the perichondrium preserved intact in situ. The perichondrium was sutured to form a perichondrial pocket and part of the excised costal cartilage was cut into 0.5 mm cartilage blocks and returned to the perichondrial pocket of left side. The animals were sacrificed 16 weeks postoperatively and the regenerated and a piece native costal cartilage was harvested for morphological and three point bending test. Results There was no remarkable chest wall deformity in all animals, and there were no apparent differences in the appearance of the regenerated cartilage with and without reimplantation autologous cartilage blocks. The elastic modulus of native cartilage was significantly higher than the regenerated cartilage. The stiffness of regenerated cartilage without reimplantation was higher than that of with reimplantation, but this difference was not significant. Conclusions The stiffness of regenerated cartilage was significantly lower than the native cartilage. Reimplantation of autologous cartilage blocks was not superior to that without reimplantation in regard to restoring the volume defect and strengthening the regenerated cartilage.

IntroductionThe presence of atrial septal defect (ASD) or ventricular septal defect (VSD) significantly affects children’s quality of life and, if not treated adequately, can contribute to increased mortality. In this study, we evaluated and compared the health-related quality of life (HRQL) of children who underwent treatment using either minimally invasive closure (MIC) or interventional closure (IC).Materials and methodsIn this observational and comparative study 199 children (2 to 4.5 years of age) underwent closure treatment for simple ASD or VSD at the Children’s Hospital of Chongqing Medical University between February 2021 and September 2021. Of these, 116 were treated with IC and 83 with MIC. Both preoperative and postoperative HRQL scores were assessed using the PedsQLTM3.0 Cardiac Module and the children were followed up at 3 and 6 months after surgery.ResultsThe two groups did not differ significantly in terms of demographics, baseline clinical characteristics, or pre-operative data. The duration of anesthesia (45 mins vs. 109 mins), procedures (25 mins vs. 48 mins), and length of postoperative hospital stay (4.32 days vs. 6.87 days) in the IC group were significantly less than in the MIC group (P < 0.001). The incidence of postoperative pneumonia in the VSD patients who underwent MIC was significantly higher than in those who underwent IC treatment (28.9% vs. 0 percent, P < 0.001). The HRQL scores increased significantly in both groups following treatment and follow-up evaluations (P < 0.001). The mean HRQL score of the IC group 3 months after treatment was significantly higher than that of the MIC group (88.9 vs. 85.7, P < 0.001), indicating a significant increase from the baseline score compared with the MIC group (5.4 vs. 2.6, P < 0.001). The IC group also showed higher scores than the MIC group (P < 0.05) in the dimensions of “Heart Problems and Treatment,” “Treatment Anxiety,” and “Cognitive Problems,” with higher scores indicating fewer problems.ConclusionThe health-related quality of life in children with ASD and VSD improved continuously regardless of IC or MIC intervention. However, IC led to better HRQL in the early postoperative stage.

Chrysanthemum is an important functional plant that is used for food, medicine and tea. Functional chrysanthemums become infected with viruses all around the world, seriously lowering their quality and yield. Viral infection has become an important limiting factor in chrysanthemum production. Functional chrysanthemum is often propagated asexually by cutting during production, and viral infection of seedlings is becoming increasingly serious. Chrysanthemums can be infected by a variety of viruses causing different symptoms. With the development of biotechnology, virus detection and virus-free technologies for chrysanthemum seedlings are becoming increasingly effective. In this study, the common virus species, virus detection methods and virus-free technology of chrysanthemum infection are reviewed to provide a theoretical basis for virus prevention, treatment and elimination in functional chrysanthemum.

Abstract Background Canine distemper caused by canine distemper virus that belongs to the Morbillivirus genus of the Paramyxoviridae family is still a global epidemic significant infectious disease, especially in pet dogs in China and serious harm to the development of the dog industry. It has been known that apoptosis caused by the canine distemper virus can show in culture cells, lymphoid tissues, and the cerebellum. However, its occurrence in brain tissue cells remains unclear. To investigate the relationship among canine distemper infecting brain tissues, apoptosis in brain tissue cells, and demyelinating pathogenesis was investigated. Methods 16 naturally infected dogs that exhibited clinical signs of CD and tested positive for the anti-CDV monoclonal antibody and six healthy dogs that served as the control, were used in the research. Brain specimens were divided into the cerebrum, brain stem, and cerebellum embedded in paraffin and made the sections respectively. Approximately 5 µm-thick sections were stained by hematoxylin–eosin, methyl green pyronin, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling technique, and immunohistochemistry. CDV nucleocapsid protein was detected by immune streptavidin-biotinylated peroxidase complex. Results Alterations in the brain tissues of CDV-infected dogs involved both various cells and nerve fibers. CDV had varying degrees of cytotropism to all brain tissue cells; apoptosis also occurred in all brain cells, especially in the endothelia of cerebral vessels, astrocytes, oligodendrocytes, and ependymal cells, the more serious infection, the more obvious apoptosis. Serious infections also involved the pyramidal and Purkinje cells. The nervous fibers exhibited demyelinating lesions (showed small multifocal vacuole), and some axonal neuron atrophy gradually disappeared (formed large vacuole). Conclusions Apoptosis in brain tissue cells was mainly related to the propagation path and cytotropism of CDV. The apoptosis of astrocytes, oligodendrocytes, and some neurons may play a significant role in the demyelinating pathogenesis in dogs with acute canine distemper. A lot of diverse nervous signs shown in the clinic may be related to different neuron apoptosis.

Abstract Background Metastasis represents the leading cause of death in patients with breast cancer. Traditional Chinese medicine is particularly appreciated for metastatic diseases in Asian countries due to its benefits for survival period prolongation and immune balance modulation. However, the underlying molecular mechanisms remain largely unknown. This study aimed to explore the antimetastatic effect and immunomodulatory function of a clinical formula Aiduqing (ADQ). Methods Naive CD4+ T cells, regulatory T cells (Tregs), and CD8+ T cells were sorted by flow cytometry. Then, breast cancer cells and these immune cells were co-cultured in vitro or co-injected into mice in vivo to simulate their coexistence. Flow cytometry, ELISA, qPCR, double luciferase reporter gene assay, and chromatin immunoprecipitation assay were conducted to investigate the immunomodulatory and antimetastatic mechanisms of ADQ. Results ADQ treatment by oral gavage significantly suppressed 4T1-Luc xenograft growth and lung metastasis in the orthotopic breast cancer mouse model, without noticeable hepatotoxicity, nephrotoxicity, or hematotoxicity. Meanwhile, ADQ remodeled the immunosuppressive tumor microenvironment (TME) by increasing the infiltration of tumor-infiltrating lymphocytes (TILs) and cytotoxic CD8+ T cells, and decreasing the infiltration of Tregs, naive CD4+ T cells, and tumor-associated macrophages (TAMs). Molecular mechanism studies revealed that ADQ remarkably inhibited CXCL1 expression and secretion from TAMs and thus suppressed the chemotaxis and differentiation of naive CD4+ T cells into Tregs, leading to the enhanced cytotoxic effects of CD8+ T cells. Mechanistically, TAM-derived CXCL1 promoted the differentiation of naive CD4+ T cells into Tregs by transcriptionally activating the NF-κB/FOXP3 signaling. Lastly, mouse 4T1-Luc xenograft experiments validated that ADQ formula inhibited breast cancer immune escape and lung metastasis by suppressing the TAM/CXCL1/Treg pathway. Conclusions This study not only provides preclinical evidence supporting the application of ADQ in inhibiting breast cancer metastasis but also sheds novel insights into TAM/CXCL1/NF-κB/FOXP3 signaling as a promising therapeutic target for Treg modulation and breast cancer immunotherapy. Video Abstract

Cardiac Troponin I (cTnI) is a subunit of the thin filament involved in regulation of heart contraction. Mutated cTnI accounts for most genetic mutations associated with restrictive cardiomyopathy (RCM). We previously found phosphodiesterase 4D (PDE4D) decreased in RCM mice with cTnIR193H mutation and the mutant cTnI might be involved in PDE4D reduction. This study aims to elucidate a novel role of cTnIR193H mutant as a gene regulator. Overexpression of cTnIR193H mutant in cardiomyocytes showed decrease in PDED4D protein expression, while the enrichment of histone deacetylase 1 (HDAC1) was increased along with decreases in acetylated lysine 4 (acH3K4) and 9 (acH3K9) levels in the PDE4D promoter. HDAC1 overexpression could also downregulate PDE4D via reducing acH3K4 and acH3K9 levels. Co-IP assays showed that cTnIR193H mutant owed increased binding ability to HDAC1 compared with wild type cTnI. EGCG as a HDAC1 inhibitor could diminish the strength of cTnIR193H-HDAC1 interactions and alleviate the reduction in PDE4D expression. Together, our data indicated that cTnIR193H mutant could repress PDE4D expression in cardiomyocytes through HDAC1 associated histone deacetylation modification. Unlike the typical function of cTnI in cytoplasm, our study suggested a novel role of cTnI mutants in nuclei in regulating gene expression.

Abstract Background This study investigated the effect of melatonin (MT) on cell cycle (G1/S/G2/M) of parthenogenetic zygotes developed from vitrified-warmed mouse metaphase II (MII) oocytes and elucidated the potential mechanism of MT action in the first cleavage of embryos. Results After vitrification and warming, oocytes were parthenogenetically activated (PA) and in vitro cultured (IVC). Then the spindle morphology and chromosome segregation in oocytes, the maternal mRNA levels of genes including Miss, Doc1r, Setd2 and Ythdf2 in activated oocytes, pronuclear formation, the S phase duration in zygotes, mitochondrial function at G1 phase, reactive oxygen species (ROS) level at S phase, DNA damage at G2 phase, early apoptosis in 2-cell embryos, cleavage and blastocyst formation rates were evaluated. The results indicated that the vitrification/warming procedures led to following perturbations 1) spindle abnormalities and chromosome misalignment, alteration of maternal mRNAs and delay in pronucleus formation, 2) decreased mitochondrial membrane potential (MMP) and lower adenosine triphosphate (ATP) levels, increased ROS production and DNA damage, G1/S and S/G2 phase transition delay, and delayed first cleavage, and 3) increased early apoptosis and lower levels of cleavage and blastocyst formation. Our results further revealed that such negative impacts of oocyte cryopreservation could be alleviated by supplementation of warming, recovery, PA and IVC media with 10− 9 mol/L MT before the embryos moved into the 2-cell stage of development. Conclusions MT might promote cell cycle progression via regulation of MMP, ATP, ROS and maternal mRNA levels, potentially increasing the first cleavage of parthenogenetic zygotes developed from vitrified–warmed mouse oocytes and their subsequent development.

Patients with spread through air spaces (STAS) have worse postoperative survival and a higher recurrence rate in lung adenocarcinoma, even in the earliest phases of the disease. At present, the molecular pathogenesis of STAS is not well understood. Therefore, to illustrate the underlying pathogenic mechanism of STAS, we accomplished a comprehensive analysis of a microarray dataset of STAS. Differential expression analysis revealed 841 differentially expressed genes (DEGs) between STAS_positive and STAS_negative groups. Additionally, we acquired two hub genes associated with survival. Gene set variation analysis (GSVA) confirmed that the main differential signaling pathways between the two groups were hypoxia VHL targets, PKC, and pyrimidine metabolism pathways. Analysis of immune activity showed that the increased expression of MHC-class-Ⅰ was observed in the STAS_positive group. These findings provided novel insights for a better knowledge of pathogenic mechanisms and potential therapeutic markers for STAS treatment.

Estradiol represents a key steroid ovarian hormone that not only plays a vital role in ovarian follicular development but also is associated with many other reproductive functions. Our primary study revealed that miR-574 expression decreased in porcine granulosa cells during development from small to large follicles, and the increase of ERK1/2 phosphorylation accompanies this change. Since it has been well established that the ERK1/2 activity is tightly associated with granulosa cell functions, including ovarian hormone production, we thus further investigate if the miRNA is involved in the regulation of estradiol production in granulosa cells. We found that overexpression of miR-574 decreased phosphorylated ERK1/2 without affecting the level of ERK1/2 protein, and on the other hand, the inhibition of miR-574 increased phosphorylated ERK1/2 level (P

China has pledged to achieve carbon neutrality in 2060. Here the authors find a promising option to abate 1.0 Gt CO2-eq yr− 1 of carbon emissions at a marginal cost of $69 (t CO2-eq)−1 by retrofitting 222 GW of coal power plants to co-fire with biomass and upgrading to CCS operation across 2836 counties in China.

Abstract Nuclear small RNAs have emerged as an important subset of non-coding RNA species that are capable of regulating gene expression. A type of small RNA, microRNA (miRNA) have been shown to regulate development of the ovarian follicle via canonical targeting and translational repression. Little has been done to study these molecules at a subcellular level. Using cell fractionation and high throughput sequencing, we surveyed cytoplasmic and nuclear small RNA found in the granulosa cells of the pig ovarian antral preovulatory follicle. Bioinformatics analysis revealed a diverse network of small RNA that differ in their subcellular distribution and implied function. We identified predicted genomic DNA binding sites for nucleus-enriched miRNAs that may potentially be involved in transcriptional regulation. The small nucleolar RNA (snoRNA) SNORA73, known to be involved in steroid synthesis, was also found to be highly enriched in the cytoplasm, suggesting a role for snoRNA species in ovarian function. Taken together, these data provide an important resource to study the small RNAome in ovarian follicles and how they may impact fertility.

A large amount of glyphosate enters the soil at a high frequency, forming “pseudo-persistent” pollutants that, in turn, threaten soil ecological function and crop growth. Earthworm casts (EWCs) are a sound organic alternative to chemical fertilizers to promote crop growth. Dissolved organic matter from EWCs (EWC-DOM) is supposed to be a more mobile and bioavailable fraction. However, the effect of EWC-DOM on the phytotoxicity of glyphosate remains largely unknown. This study examines glyphosate-induced oxidative stress and its impact on antioxidant and detoxification enzymes in citrus plants grown in soils with and/or without EWC-DOM. The results suggest that EWC-DOM could reduce the membrane lipid peroxidation level, thus slowing down the aging of plants in order to maintain stronger resilience, with more active antioxidant enzymes (including SOD, POD, and CAT) and detoxification enzymes (including GST, laccase, CPR, and UGTs) that could effectively remove reactive oxygen species (ROS) caused by glyphosate stress, thereby alleviating the damage of ROS accumulation on plant tissues. Our data indicate that incorporating EWC-DOM should be a sound way to protect citrus plants from the phytotoxicity caused by using glyphosate for orchard weeding. This has major implications for the sustainable and healthy development of citrus production.

Alzheimer’s disease (AD) is a common neurodegenerative disease that currently has no known cure. Intravenous immunoglobulin (IVIG), which contains AD-related antibodies and has anti-inflammatory properties, has shown potential as a treatment for AD. However, the efficacy of clinical trials involving AD patients treated with IVIG has been inconsistent. Our previous study found that different IVIGs had significantly varied therapeutic effects on 3xTg-AD mice. In order to investigate the relationship between the composition and function of IVIG and its efficacy in treating AD, we selected three IVIGs that showed notable differences in therapeutic effects. Then, the concentrations of specific antibodies against β-amyloid (Aβ)42, tau, and hyperphosphorylated tau (p-tau) in three IVIGs, as well as their effects on systemic inflammation induced by lipopolysaccharide (LPS) in Balb/c mice, were analyzed and compared in this study. The results indicated that these IVIGs differed greatly in anti-Aβ42/tau antibody concentration and anti-p-tau ratio, and improved LPS-stimulated peripheral inflammation, liver and kidney injury, and neuroinflammation in Balb/c mice to varying degrees. Combined with our previous results, the efficacy of IVIG against AD may be positively correlated with its level of AD-related antibodies and anti-inflammatory ability. AD-related antibody analysis and functional evaluation of IVIG should be given sufficient attention before clinical trials, as this may greatly affect the therapeutic effect of AD treatment.

Abstract Background Breast cancer (BC) remains a prevalent and common form of cancer with high heterogeneity. Making efforts to explore novel molecular biomarkers and serve as potential disease indicators, which is essential to effectively enhance the prognosis and individualized treatment of BC. FBXO proteins act as the core component of E3 ubiquitin ligase, which play essential regulators roles in multiple cellular processes. Recently, research has indicated that FBXOs also play significant roles in cancer development. However, the molecular functions of these family members in BC have not been fully elucidated. Methods In this research, we investigated the expression data, survival relevance and mutation situation of 10 FBXO members (FBXO1, 2, 5, 6, 16, 17, 22, 28, 31 and 45) in patients with BC from the Oncomine, GEPIA, HPA, Kaplan–Meier Plotter, UALCAN and cBioPortal databases. The high transcriptional levels of FBXO1 in different subtypes of BC were verified by immunohistochemical staining and the specific mutations of FBXO1 were obtained from COSMIC database. Top 10 genes with the highest correlation to FBXO1 were identified through cBioPortal and COXPRESdb tools. Additionally, functional enrichment analysis, PPI network and survival relevance of FBXO1 and co-expressed genes in BC were obtained from DAVID, STRING, UCSC Xena, GEPIA, bc-GenExMiner and Kaplan–Meier Plotter databases. FBXO1 siRNAs were transfected into MCF-7 and MDA-MB-231 cell lines. Expression of FBXO1 in BC cell lines was detected by western-blot and RT-qPCR. Cell proliferation was detected by using CCK-8 kit and colony formation assay. Cell migration was detected by wound‐healing and transwell migration assay. Results We found that FBXO2, FBXO6, FBXO16 and FBXO17 were potential favorable prognostic factors for BC. FBXO1, FBXO5, FBXO22, FBXO28, FBXO31 and FBXO45 may be the independent poor prognostic factors for BC. All of them were correlated to clinicopathological staging. Moreover, knockdown of FBXO1 in MCF7 and MDA-MB-231 cell lines resulted in decreased cell proliferation and migration in vitro. We identified that FBXO1 was an excellent molecular biomarker and therapeutic target for different molecular typing of BC. Conclusion This study implies that FBXO1, FBXO2, FBXO5, FBXO6, FBXO16, FBXO17, FBXO22, FBXO28, FBXO31 and FBXO45 genes are potential clinical targets and prognostic biomarkers for patients with different molecular typing of BC. In addition, the overexpression of FBXO1 is always found in breast cancer and predicts disadvantageous prognosis, implicating it could as an appealing therapeutic target for breast cancer patients.

Abstract Aquaculture has become imperative to cover the demands for dietary animal protein. Simultaneously, it has to overcome prejudices from excessive use of antibiotics and environmental impacts. Natural supplements are traditionally applied orally. In this study, we demonstrated another pathway: the gills. Humic substances are immunostimulants and a natural part of every aquatic ecosystem, making them ideal to be used as bath stimulants. Five and 50 mg C/L of a fulvic acid-rich humic substance was added for 28 days to the water of juvenile rainbow trout (Oncorhynchus mykiss). This fulvic acid is characterized by a high content of phenolic moieties with persistent free radicals and a high electron exchange capacity. The high concentration of the fulvic acid significantly increased growth and reduced the food conversion ratio and the response to a handling-stressor. Phagocytosis and potential killing activity of head kidney leukocytes were increased, as well as the total oxyradical scavenging capacity (TOSC) and lysozyme activity in the gills. In conclusion, immunostimulation via gills is possible with our fulvic acid, and the high phenolic content improved overall health and stress resistance of fish.

Multilineage differentiating stress enduring cells (Muse cells), double positive for SSEA-3 and CD105, can be isolated by fluorescence-activated cell sorting (FACS) or sever cellular conditions from dermal fibroblasts, bone marrow stem cells (BMSCs), adipose tissue derived stem cells (ADSCs), fresh bone marrow and liposuction fat. When cultured in a single-cell suspension, Muse cells can grow into characteristic cell clusters. Muse cells maintain pluripotency as evidenced by pluripotent markers in vitro. Besides, Muse cells have no tumorigenesis up to 6 months in SCID mice. Muse cells differentiate into cells representative of all three germ layers both spontaneously and under specific induction. In comparison to mesenchymal stem cells (MSCs), Muse cells show higher homing and migration capabilities to damaged sites which is predominantly attributed to S1P–S1PR2 axis. The regenerative effects of Muse cells have been demonstrated by many models in vivo or in vitro, including stroke, intracerebral hemorrhage, myocardial infarction, aortic aneurysm, lung injuries, liver fibrosis, focal segmental glomerulosclerosis, osteochondral defects and skin ulcer. In general, migration, differentiation and paracrine play a pivotal role in the regeneration capability. Here we review the isolation, core properties, preclinical studies as well as the underling molecular and cellular details to highlight their regenerative potential.

Background and AimHeart failure in children differs substantially from the adult population. Clinical characteristics of pediatric diastolic heart failure has rarely been reported. In this study, we aimed to summary the causes, clinical features, lab tests, and treatment effect of pediatric diastolic heart failure.MethodsThis study was a single center, retrospective study conducted in Children’s Hospital of Chongqing Medical University. Children who were diagnosed with diastolic heart failure (DHF) without systolic heart failure (SHF) between 2006 and 2014 were included. Meanwhile, SHF (without DHF) cases were also collected from 2013 to 2014.ResultsA total of 421 DHF and 42 SHF cases were included. The average age of pediatric DHF was 1.89 ± 3.29 years old, significant younger than that of SHF (4.65 ± 4.90). The top three cardiovascular causes of DHF were complex congenital heart malformations (53.4%), simple congenital heart defect (15.7%), and cardiomyopathy (7.4%). Alternatively, number of cardiomyopathy cases (57.1%) ranked first in SHF group. Simple congenital heart diseases (CHDs) rarely caused SHF. The most common symptom and sign were tachypnea and hepatomegaly in pediatric HF. Symptoms like cyanosis, feeding difficulty, be fidgety, pale, fatigue, and edema were valuable in differential diagnosis of DHF and SHF in children. B-type natriuretic peptide (BNP) increase was found in 36.9% of DHF children, and 60% in SHF patients. Sensitivity of BNP greater than 100 pg/ml in diagnosis of DHF was 0.37, and specificity of it was 0.86. Diastolic function indicators, such as E/A (early wave/late wave) ratio, IVRT (isovolumic relaxation time) were significant recovered after treatment in DHF patients. Less therapeutic benefits were achieved in children with cardiomyopathy induced DHF, in compared with non-cardiomyopathy patients.ConclusionPediatric DHF and SHF were largely different in primary causes, clinical symptoms and signs and short-term prognosis. There was a limit diagnostic value of BNP with 100 pg/ml as cut-off value in pediatric DHF. Larger, multicenter studies of pediatric DHF are required in the future.

BackgroundDepression plays a significant role in mediating breast cancer recurrence and metastasis. However, a precise risk model is lacking to evaluate the potential impact of depression on breast cancer prognosis. In this study, we established a depression-related gene (DRG) signature that can predict overall survival (OS) and elucidate its correlation with pathological parameters and sensitivity to therapy in breast cancer.MethodsThe model training and validation assays were based on the analyses of 1,096 patients from The Cancer Genome Atlas (TCGA) database and 2,969 patients from GSE96058. A risk signature was established through univariate and multivariate Cox regression analyses.ResultsTen DRGs were determined to construct the risk signature. Multivariate analysis revealed that the signature was an independent prognostic factor for OS. Receiver operating characteristic (ROC) curves indicated good performance of the model in predicting 1-, 3-, and 5-year OS, particularly for patients with triple-negative breast cancer (TNBC). In the high-risk group, the proportion of immunosuppressive cells, including M0 macrophages, M2 macrophages, and neutrophils, was higher than that in the low-risk group. Furthermore, low-risk patients responded better to chemotherapy and endocrine therapy. Finally, a nomogram integrating risk score, age, tumor-node-metastasis (TNM) stage, and molecular subtypes were established, and it showed good agreement between the predicted and observed OS.ConclusionThe 10-gene risk model not only highlights the significance of depression in breast cancer prognosis but also provides a novel gene-testing tool to better prevent the potential adverse impact of depression on breast cancer prognosis.

Keratin 8 (KRT8) is the major component of the intermediate filament cytoskeleton and aberrant expression in multiple tumors. However, the role of KRT8 in lung adenocarcinoma (LUAD) remains unclear. In the present study, KRT8 expression was found to be upregulated along with prognosis and metastasis in LUAD. Kaplan–Meier analysis presented that the 5-year OS and DSS rates were significantly better among patients with low KRT8 expression compared to those with high expression. Correlation analysis showed that KRT8 expression was significantly associated with gender (P = 0.027), advanced T stage (P = 0.001), advanced N stage (P = 0.048), and advanced pathologic stage (P = 0.025). Univariate Cox analysis demonstrated that KRT8 was a predictor of OS [hazard ratio (HR) = 1.526; 95% confidence interval (CI) 1.141–2.040; P = 0.004] and DSS (HR = 1.625; 95% CI 1.123–2.353; P = 0.010) in the TCGA database. Importantly, downregulation of KRT8 obviously suppressed cell proliferation, cell migration, invasion, and EMT as well as induced cell apoptosis. KRT8 knockdown significantly inhibited NF-κB signaling, suggesting a potential mechanism. Overall, our results indicated that KRT8 could regulate lung carcinogenesis and may serve as a potential target for antineoplastic therapies.

Mental health disorders are prevalent among biomedical students, and scientific research is one of their main activities, yet less is known about the relationship between research activities and mental health among these students. The aim of this cross-sectional study was to assess the associations between research activities and mental health and to identify the potential risk factors for anxiety and depression among biomedical students in China. This study enrolled 1,079 participants between November 2020 and December 2020 from 29 Chinese provinces and collected participants' basic characteristics, work situations, scientific achievements, and potential stress sources via an online questionnaire. Anxiety and depression were evaluated by two widely used scales, the Generalized Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9), respectively. The study also assessed the associations between scientific research duration and mental health. Univariate and multivariate analyses were performed to identify the predictors of anxiety and depression. Among the participants, 39.02% scored as having moderate to severe anxiety, and 37.54% scored as having moderate to severe depression. When the Youden index reached its maximum, the optimal cutoff was 7.17 h for the GAD-7 and 6.83 h for the PHQ-9. After adjustment for confounders, a longer research work duration was significantly associated with a higher anxiety [odds ratio (OR) = 1.32, 95% confidence interval (CI): 1.21–1.44, p < 0.01] and depression (OR = 1.27, 95% CI: 1.17–1.39, p < 0.01). Of all the participants working for 7 h a day, 37.04% had already published at least one paper and 25.93% had at least one Science Citation Index paper. Anxiety and depression are common among biomedical students. The research work duration of 7 h a day is the best cutoff for mental health, and it is associated with acceptable scientific research achievements. Not more than 7 h a day on research is recommended for biomedical students to maintain a balance between mental health and scientific research achievements.

Dumasia taxonomy and classification have long been problematic. Species within this genus have few morphological differences and plants without flowers or fruits are difficult to accurately identify. In this study, we evaluated the ability of six DNA barcoding sequences, one nuclear (ITS) and five chloroplast regions (trnH-psbA, matK, rbcL, trnL-trnF, psbB-psbF), to efficiently identify Dumasia species. Most single markers or their combinations identify obvious barcoding gaps between intraspecific and interspecific genetic variation. Most combined analyses including ITS showed good species resolution and identification efficiency. We therefore suggest that ITS alone or a combination of ITS with any cpDNA marker are most suitable for DNA barcoding of Dumasia. The phylogenetic analyses clearly indicated that Dumasia yunnanensis is not monophyletic and is separated as two independent branches, which may result from cryptic differentiation. Our results demonstrate that molecular data can deepen the comprehension of taxonomy of Dumasia and provide an efficient approach for identification of the species.

Abstract Introduction In collaboration with the Alberta Medical Association’s Physician Learning Program we developed individualized physician reports and held a group feedback session on rheumatoid arthritis (RA) performance measures (PM) to facilitate treat-to-target (T2T) strategies and evaluated physician experiences with this process. Methods 5 PMs addressing T2T concepts from an established Canadian quality framework were operationalized for physician practice reports at 2 university-affiliated rheumatology clinics. Rheum4U, a quality improvement and research platform, was the data source. The audit results were reviewed in a facilitated group feedback session. Rheumatologists provided experiential feedback on the process through survey and/or an interview. Transcripts from interviews were analyzed using a 6-step thematic analysis. Results 11 of 12 eligible rheumatologists consented to receive practice reports and provided feedback through surveys (n = 5) and interviews (n = 6). The practice reports from Rheum4U (n = 448 patients) revealed high rates of yearly follow-up (> 85%, PM1) and 100% performance on documentation of disease activity at ≥ 50% of visits (PM2). Only 34% of patients were seen within 3 months if not in remission (PM3) with 62% (2017) and 69% (2018) of those with active RA achieving a LDA state within 6 months (PM4). Approximately 70% of patients were in remission at any time point (PM5). All survey respondents agreed or strongly agreed comparison to peers was valuable and helped them reflect on their practice. Several strategies for improvement were identified, including but not limited to, leveraging of electronic records for future audit and feedback reports, providing additional granularity of results, additional stratification of results, and using high-performing peers as the comparator rather than the group mean. Conclusions Audit and feedback was perceived by clinicians as a useful strategy for evaluating T2T efforts in RA. Future work will focus on longitudinal evaluation of the clinical impact of this quality improvement initiative.

The limestone regions of Yunnan-Guangxi-Guizhou in southern and southwestern China are regarded as some of biodiversity’s hotspots for China’s Gesneriaceae where numerous rare new species of Primulina have been, or are being, described over the past two decades. Primulina flexusa, a new lithophytic species of Gesneriaceae from a limestone hill in a Karst area, from Guizhou, China, is described here with color photographs. It is similar to P. curvituba, but can be easily distinguished by a combination of characteristics, especially in the shape and length of its capsule. We found only one population with approximately 100 mature individuals at the type locality. This new species is provisionally assessed as Critically Endangered [CR C1] by using IUCN criteria.

Abstract Background Mammary Paget’s disease (MPD) is an uncommon cutaneous intraepithelial malignancy with ulceration of the nipple or areola. Its pathogenesis and genomic mutation remain largely unknown and no cell lines are established from primary tumors. Methods We collected surgical tumor specimens from a 65-year-old Chinese woman diagnosed with MPD and established patient-derived breast cancer (BC) organoids from MPD using organoid culture technology. Results We successfully propagated BC organoids from a patient with MPD for more than 6 months. The organoids were cultured for long-term expansion without any change in spherical organoid morphology. Besides, the spherical organoid morphology did not change when they underwent cryopreservation after resuscitation. The H&E staining and immunohistochemistry analyses showed the similar morphological and histological features of the organoids compared with their paired original BC tissues. The organoids retained positive expression of breast cancer biomarkers: estrogen receptor, progesterone receptor, antigen Ki-67 and negative expression of human epidermal growth factor receptor 2. We also showed that MPD organoids recapitulated the unique genomic landscape including copy number alterations, mutational load, mutational signatures and cancer gene mutations by whole genome sequencing. In situ senescence-associated acid beta galactosidase assay confirmed senescence phenomenon existed in the process of organoids culture and there was no significant difference in the proportion of senescent organoids after organoid passage and resuscitation. Conclusions Our results suggested that an effective platform for ex vivo BC organoids from MPD patients could be used to explore clinicopathological and genomic characteristics of these patients.

Abstract Background Microtia is a congenital anomaly of ear that ranges in severity from mild structural abnormalities to complete absence of the outer ears. Concha-type microtia is considered to be a mild form. The H6 family homeobox 1 transcription factor gene (HMX1) plays an important role in craniofacial structures development. Copy number variations (CNVs) of a downstream evolutionarily conserved enhancer region (ECR) of Hmx1 associated with ear and eye abnormalities have been reported in different animals, but not yet in human. To date, no genetic defects responsible for isolated human microtia has been reported except for mutations in HOXA2. Here we recruited five Chinese families with isolated bilateral concha-type microtia, and attempt to identify the underlying genetic causes. Methods Single Nucleotide polymorphism (SNP) array was performed to map the disease locus and detect CNVs on a genome scale primarily in the largest family (F1). Whole genome sequencing was performed to screen all SNVs and CNVs in the candidate disease locus. Array comparative genomic hybridization (aCGH) was then performed to detect CNVs in the other four families, F2-F5. Quantitative real-time polymerase chain reaction (qPCR) was used to validate and determine the extent of identified CNVs containing HMX1-ECR region. Precise breakpoints in F1 and F2 were identified by gap-PCR and sanger sequencing. Dual-luciferase assays were used to detect the enhancer function. qPCR assays were also used to detect HMX1-ECR CNVs in 61 patients with other types mictrotia. Results Linkage and haplotype analysis in F1 mapped the disease locus to a 1.9 Mb interval on 4p16.1 containing HMX1 and its downstream ECR region. Whole genome sequencing detected no potential pathogenic SNVs in coding regions of HMX1 or other genes within the candidate disease locus, but it detected a 94.6 Kb duplication in an intergenic region between HMX1 and CPZ. aCGH and qPCRs also revealed co-segregated duplications in intergenic region downstream of HMX1 in the other four families. The 21.8 Kb minimal overlapping region encompassing the core sequences consensus with mouse ECR of Hmx1. Luciferase assays confirmed the enhancer function in human sequences, and proved that HOXA2 could increase its enhancer activity. No CNVs were detected in HMX1-ECR regions in 61 patients with other type of microtia. Conclusion Duplications involving long range HMX1 enhancers are associated with human isolated bilateral concha-type microtia. We add to evidences in human that copy number variations in HMX1-ECR associates with ear malformations, as in other species. This study also provides an additional example of functional conserved non-coding elements (CNEs) in humans.

Jasminum parceflorum (Oleaceae), a new species from tropical limestone habitats in Yunnan, China, is described and illustrated here. The new species is similar to J. pierreanum and J. rarum, but can be distinguished by its linear calyx lobes, dry calyces without ridges, terminal 1 (or 3)-flowered cymes and axillary solitary flowers.

Abstract Background Only a small proportion of anterior cruciate ligament (ACL) tears are diagnosed on initial healthcare consultation. Current clinical guidelines do not acknowledge that primary point-of-care practitioners rely more heavily on a clinical history than special clinical tests for diagnosis of an ACL tear. This research will assess the accuracy of combinations of patient-reported variables alone, and in combination with clinician-generated variables to identify an ACL tear as a preliminary step to designing a primary point-of-care clinical decision support tool. Methods Electronic medical records (EMRs) of individuals aged 15–45 years, with ICD-9 codes corresponding to a knee condition, and confirmed (ACL+) or denied (ACL−) first-time ACL tear seen at a University-based Clinic between 2014 and 2016 were eligible for inclusion. Demographics, relevant diagnostic indicators and ACL status based on orthopaedic surgeon assessment and/or MRI reports were manually extracted. Descriptive statistics calculated for all variables by ACL status. Univariate between group comparisons, clinician surveys (n = 17), availability of data and univariable logistic regression (95%CI) were used to select variables for inclusion into multivariable logistic regression models that assessed the odds (95%CI) of an ACL-tear based on patient-reported variables alone (consistent with primary point-of-care practice), or in combination with clinician-generated variables. Model performance was assessed by accuracy, sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios (95%CI). Results Of 1512 potentially relevant EMRs, 725 were included. Participant median age was 26 years (range 15–45), 48% were female and 60% had an ACL tear. A combination of patient-reported (age, sport-related injury, immediate swelling, family history of ACL tear) and clinician-generated (Lachman test result) variables were superior for ACL tear diagnosis [accuracy; 0.95 (90,98), sensitivity; 0.97 (0.88,0.98), specificity; 0.95 (0.82,0.99)] compared to the patient-reported variables alone [accuracy; 84% (77,89), sensitivity; 0.60 (0.44,0.74), specificity; 0.95 (0.89,0.98)]. Conclusions A high proportion of individuals without an ACL tear can be accurately identified by considering patient-reported age, injury setting, immediate swelling and family history of ACL tear. These findings directly inform the development of a clinical decision support tool to facilitate timely and accurate ACL tear diagnosis in primary care settings.

Abstract Background Papillary carcinoma is an uncommon type of breast cancer. Additionally, patients with huge breast papillary carcinoma are extremely rare in clinical practice. To improve therapeutic effect on such patients, it is urgent to explore biologically and clinically relevant models of the disease to discover effective drugs. Methods We collected surgical tumor specimens from a 63-year-old Chinese woman who has been diagnosed breast papillary carcinoma. The tumor was more than 15 cm in diameter, and applied to establish patient-derived papillary carcinoma organoids that could continuously propagate for more than 6 months. Results The papillary carcinoma organoids matched the histological characteristics of orginal tumor by H&E staining identification, and maintained the expression of the breast cancer biomarkers by IHC, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2) and antigen Ki-67 (Ki67). In addition, we performed a 3-D drug screening to examine the effects of endocrine drugs (Fulvestrant, Tamoxifen) and targeted therapy drugs (Palbociclib, Everolimus, BKM120) on breast papillary carcinoma in the mimic in vivo environment. The drug sensitivities of our breast papillary carcinoma organoids were investigated as follows, Fulvestrant (IC50 0.275 μmol), Palbociclib (IC50 2.21 μmol), BKM120 (IC50 3.81 μmol), Everolimus (IC50 4.45 μmol), Tamoxifen (IC50 19.13 μmol). Conclusions These results showed that an effective organoid platform for 3-D in vitro culture of breast cancer organoids from patients with breast papillary carcinoma could be used to identify possible treatments, and might be commonly applied to explore clinicopathological characteristics of breast papillary carcinoma.