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Abstract Background Auriculocondylar syndrome (ARCND) is an extremely rare autosomal dominant or recessive condition that typically manifests as question mark ears (QMEs), mandibular condyle hypoplasia, and micrognathia. Severe dental and maxillofacial malformations present considerable challenges in patients’ lives and clinical treatment. Currently, only a few ARCND cases have been reported worldwide, but most of them are related to genetic mutations, clinical symptoms, and ear correction; there are few reports concerning the treatment of dentofacial deformities. Case presentation Here, we report a rare case of ARCND in a Chinese family. A novel insertional mutation in the guanine nucleotide-binding protein alpha-inhibiting activity polypeptide 3 (GNAI3) was identified in the patient and their brother using whole-exome sequencing. After a multidisciplinary consultation and examination, sequential orthodontic treatment and craniofacial surgery, including distraction osteogenesis and orthognathic surgery, were performed using three-dimensional (3D) digital technology to treat the patient’s dentofacial deformity. A good prognosis was achieved at the 5-year follow-up, and the patient returned to normal life. Conclusions ARCND is a monogenic and rare condition that can be diagnosed based on its clinical triad of core features. Molecular diagnosis plays a crucial role in the diagnosis of patients with inconspicuous clinical features. We present a novel insertion variation in GNAI3, which was identified in exon 2 of chromosome 110116384 in a Chinese family. Sequential therapy with preoperative orthodontic treatment combined with distraction osteogenesis and orthognathic surgery guided by 3D digital technology may be a practical and effective method for treating ARCND.

Abstract Tomato is a popular vegetable worldwide; its production is highly threatened by infection with the potato spindle tuber viroid (PSTVd). We obtained the full‐length genome sequence of previously conserved PSTVd and inoculated it on four genotypes of semi‐cultivated tomatoes selected from a local tomato germplasm resource. SC‐5, which is a PSTVd‐resistant genotype, and SC‐96, which is a PSTVd‐sensitive genotype, were identified by detecting the fruit yield, plant growth, biomass accumulation, physiological indices, and PSTVd genome titer after PSTVd inoculation. A non‐target metabolomics study was conducted on PSTVd‐infected and control SC‐5 to identify potential anti‐PSTVd metabolites. The platform of liquid chromatography‐mass spectrometry detected 158 or 123 differential regulated metabolites in modes of positive ion or negative ion. Principal component analysis revealed a clear separation of the global metabolite profile between PSTVd‐infected leaves and control regardless of the detection mode. The potential anti‐PSTVd compounds, xanthohumol, oxalicine B, indole‐3‐carbinol, and rosmarinic acid were significantly upregulated in positive ion mode, whereas echinocystic acid, chlorogenic acid, and 5‐acetylsalicylic acid were upregulated in negative ion mode. Xanthohumol and echinocystic acid were detected as the most upregulated metabolites and were exogenously applied on PSTVd‐diseased SC‐96 seedlings. Both xanthohumol and echinocystic acid had instant and long‐term inhibition effect on PSTVd titer. The highest reduction of disease symptom was induced by 2.6 mg/L of xanthohumol and 2.0 mg/L of echinocystic acid after 10 days of leaf spraying, respectively. A superior effect was seen on echinocystic acid than on xanthohumol. Our study provides a statistical basis for breeding anti‐viroid tomato genotypes and creating plant‐originating chemical preparations to prevent viroid disease.

Radish (Raphanus sativus L.) is an important root vegetable crop belonging to the Brassicaceae family. Anthocyanin rich radish varieties are popular among consumers because of their bright color and high nutritional value. However, the underlying molecular mechanism responsible for skin and flesh induce anthocyanin biosynthesis in transient overexpression, gene silencing and transcriptome sequencing were used to verify its function in radish anthocyanin accumulation, radish remains unclear. Here, we identified a long noncoding RNA LINC15957, overexpression of LINC15957 was significantly increased anthocyanin accumulation in radish leaves, and the expression levels of structural genes related to anthocyanin biosynthesis were also significantly increased. Anthocyanin accumulation and expression levels of anthocyanin biosynthesis genes were significantly reduced in silenced LINC15957 flesh when compared with control. By the transcriptome sequencing of the overexpressed LINC15957 plants and the control, 5,772 differentially expressed genes were identified. A total of 3,849 differentially expressed transcription factors were identified, of which MYB, bHLH, WD40, bZIP, ERF, WRKY and MATE were detected and differentially expressed in the overexpressed LINC15957 plants. KEGG enrichment analysis revealed the genes were significant enriched in tyrosine, L-Phenylalanine, tryptophan, phenylpropanol, and flavonoid biosynthesis. RT-qPCR analysis showed that 8 differentially expressed genes (DEGs) were differentially expressed in LINC15957-overexpressed plants. These results suggested that LINC15957 involved in regulate anthocyanin accumulation and provide abundant data to investigate the genes regulate anthocyanin biosynthesis in radish.

Radish (Raphanus sativus L.) is an economically important vegetable worldwide, but its sustainable production and breeding are highly threatened by blight disease caused by Alternaria brassicae. Melatonin is an important growth regulator that can influence physiological activities in both plants and microbes and stimulate biotic stress resistance in plants. In this study, 0-1500 μM melatonin was exogenously applied to healthy radish seedlings, in vitro incubated A. brassicae, and diseased radish seedlings to determine the effects of melatonin on host, pathogen, and host-pathogen interaction. At sufficient concentrations (0-500 μM), melatonin enhanced growth and immunity of healthy radish seedlings by improving the function of organelles and promoting the biosynthesis of antioxidant enzymes, chitin, organic acid, and defense proteins. Interestingly, melatonin also improved colony growth, development, and virulence of A. brassicae. A strong dosage-dependent effect of melatonin was observed: 50-500 μM promoted host and pathogen vitality and resistance (500 μM was optimal) and 1500 μM inhibited these processes. Significantly less blight was observed on diseased seedlings treated with 500 μM melatonin, indicating that melatonin more strongly enhanced the growth and immunity of radish than it promoted the development and virulence of A. brassicae at this treatment concentration. These effects of MT were mediated by transcriptional changes of key genes as identified by RNA-seq, Dual RNA-seq, and qRT-PCR. The results from this work provide a theoretical basis for the application of melatonin to protect vegetable crops against pathogens.

Plasmodiophora brassicae causes a serious threat to cruciferous plants including radish (Raphanus sativus L.). Knowledge on the pathogenic regularity and molecular mechanism of P. brassicae and radish is limited, especially on the metabolism level. In the present study, clubroot-susceptible and clubroot-resistant cultivars were inoculated with P. brassicae Race 4, root hairs initial infection of resting spores (107 CFU/mL) at 24 h post-inoculation and root galls symptom arising at cortex splitting stage were identified on both cultivars. Root samples of cortex splitting stage of two cultivars were collected and used for untargeted metabonomic analysis. We demonstrated changes in metabolite regulation and pathways during the cortex splitting stage of diseased roots between clubroot-susceptible and clubroot-resistant cultivars using untargeted metabonomic analysis. We identified a larger number of differentially regulated metabolites and heavier metabolite profile changes in the susceptible cultivar than in the resistant counterpart. The metabolites that were differentially regulated in both cultivars were mostly lipids and lipid-like molecules. Significantly regulated metabolites and pathways according to the P value and variable important in projection score were identified. Moreover, four compounds, including ethyl α-D-thioglucopyranoside, imipenem, ginsenoside Rg1, and 6-gingerol, were selected, and their anti-P. brassicae ability and effects on seedling growth were verified on the susceptible cultivar. Except for ethyl α-D-thioglucopyranoside, the remaining could inhibit clubroot development of varing degree. The use of 5 mg/L ginsenoside Rg1 + 5 mg/L 6-gingerol resulted in the lowest disease incidence and disease index among all treatments and enhanced seedling growth. The regulation of pathways or metabolites of carbapenem and ginsenoside was further explored. The results provide a preliminary understanding of the interaction between radish and P. brassicae at the metabolism level, as well as the development of measures for preventing clubroot.

A latent tuberculosis infection (LTBI) is a major source of active tuberculosis, and addressing an LTBI is crucial for the elimination of tuberculosis. The treatment of tuberculosis often requires a 6-month course of multidrug therapy, and for drug-resistant tuberculosis, a longer course of multidrug therapy is needed, which has many drawbacks. At present, vaccines are proposed as an adjunct to chemotherapy to protect populations with an LTBI and delay its recurrence. In this study, we analyzed the protective effect of a novel subunit vaccine, AEC/BC02, in a guinea pig latent infection model. Through the optimization of different chemotherapy durations and immunization times, it was found that 4 weeks of administration of isoniazid–rifampin tablets combined with three or six injections of the vaccine could significantly reduce the gross pathological score and bacterial load in organs and improve the pathological lesions. This treatment regimen had a better protective effect than the other administration methods. Furthermore, no drug resistance of Mycobacterium tuberculosis was detected after 2 or 4 weeks of administration of the isoniazid–rifampin tablets, indicating a low risk of developing drug-resistant bacteria during short-term chemotherapy. The above results provided the foundation for an AEC/BC02 clinical protocol.

The BCG vaccine is prepared from a weakened strain of Mycobacterium bovis (M. bovis), a bacterium closely related to Mycobacterium tuberculosis (MTB), which causes tuberculosis (TB). The vaccine was developed over 13 years, from 1908 to 1921, in the French Institut Pasteur by Léon Charles Albert Calmette and Jean-Marie Camille Guérin, who named the product Bacillus Calmette–Guérin (BCG). BCG, the only licensed vaccine currently available to prevent TB, is given to infants at high risk of TB shortly after birth to protect infants and young children from pulmonary, meningeal, and disseminated TB. The BCG vaccine, one of the safest and most widely used live attenuated vaccines in the world, recently celebrated its 100th anniversary (from 1921 to 2021); its record of use in preventing TB in China is also approaching 100 years. In 2022, a new century of BCG vaccine immunization will begin. In this article, we briefly review the history of BCG vaccine use in China, describe its current status, and offer a preliminary outlook on the future of the vaccine, to provide BCG researchers with a clearer understanding of its use in China.

Tuberculosis (TB), caused by the human pathogen Mycobacterium tuberculosis (Mtb), is an infectious disease that presents a major threat to human health. Bacillus Calmette-Guérin (BCG), the only licensed TB vaccine, is ineffective against latent TB infection, necessitating the development of further TB drugs or therapeutic vaccines. Herein, we evaluated the therapeutic effect of a novel subunit vaccine AEC/BC02 after chemotherapy in a spontaneous Mtb relapse model. Immunotherapy followed 4 weeks of treatment with isoniazid and rifapentine, and bacterial loads in organs, pathological changes, and adaptive immune characteristics were investigated. The results showed slowly increased bacterial loads in the spleen and lungs of mice inoculated with AEC/BC02 with significantly lower loads than those of the control groups. Pathological scores for the liver, spleen, and lungs decreased accordingly. Moreover, AEC/BC02 induced antigen-specific IFN-γ-secreting or IL-2-secreting cellular immune responses, which decreased with the number of immunizations and times. Obvious Ag85b- and EC-specific IgG were observed in mice following the treatment with AEC/BC02, indicating a significant Th1-biased response. Taken together, these data suggest that AEC/BC02 immunotherapy post-chemotherapy may shorten future TB treatment.

Hepatic stellate cells (HSCs) activation is essential to the pathogenesis of liver fibrosis. Exploring drugs targeting HSC activation is a promising anti-fibrotic strategy. In the present study, we found suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, prominently suppressed the activation phenotype of a human hepatic stellate cell line—LX2. The production of collagen type I and α-smooth muscle actin (α-SMA) as well as the proliferation and migration of LX2 cells were significantly reduced by SAHA treatment. To determine the molecular mechanisms underlying this suppression, genome wild gene regulation by SAHA was determined by Affymetrix 1.0 human cDNA array. Upon SAHA treatment, the abundance of 331 genes was up-regulated and 173 genes was down-regulated in LX2 cells. Bioinformatic analyses of these altered genes highlighted the high mobility group box 1 (HMGB1) pathway was one of the most relevant pathways that contributed to SAHA induced suppression of HSCs activation. Further studies demonstrated the increased acetylation of intracellular HMGB1 in SAHA treated HSCs, and this increasing is most likely to be responsible for SAHA induced down-regulation of nuclear factor kappa B1 (NF-κB1) and is one of the main underlying mechanisms for the therapeutic effect of SAHA for liver fibrosis.

Plasmodiophora brassicae causes a serious threat to cruciferous plants including radish (Raphanus sativus L.). Knowledge on the pathogenic regularity and molecular mechanism of P. brassicae and radish is limited, especially on the metabolism level. In the present study, clubroot-susceptible and clubrootresistant cultivars were inoculated with P. brassicae Race 4, root hairs initial infection of resting spores (107 CFU/mL) at 24 h post-inoculation and root galls symptom arising at cortex splitting stage were identified on both cultivars. Root samples of cortex splitting stage of two cultivars were collected and used for untargeted metabonomic analysis. We demonstrated changes in metabolite regulation and pathways during the cortex splitting stage of diseased roots between clubroot-susceptible and clubroot-resistant cultivars using untargeted metabonomic analysis. We identified a larger number of differentially regulated metabolites and heavier metabolite profile changes in the susceptible cultivar than in the resistant counterpart. The metabolites that were differentially regulated in both cultivars were mostly lipids and lipid-like molecules. Significantly regulated metabolites and pathways according to the P value and variable important in projection score were identified. Moreover, four compounds, including ethyl α-D-thioglucopyranoside, imipenem, ginsenoside Rg1, and 6-gingerol, were selected, and their anti-P. brassicae ability and effects on seedling growth were verified on the susceptible cultivar. Except for ethyl α-Dthioglucopyranoside, the remaining could inhibit clubroot development of varing degree. The use of 5 mg/L ginsenoside Rg1 + 5 mg/L 6-gingerol resulted in the lowest disease incidence and disease index among all treatments and enhanced seedling growth. The regulation of pathways or metabolites of carbapenem and ginsenoside was further explored. The results provide a preliminary understanding of the interaction between radish and P. brassicae at the metabolism level, as well as the development of measures for preventing clubroot. [ABSTRACT FROM AUTHOR]

Abstract Background The initial CT blend sign is an imaging marker that has been used to predict haematoma expansion and poor outcomes in patients with small-volume intracerebral haemorrhage (ICH). However, the association of the blend sign with the outcomes of patients undergoing surgery remains unclear. The present study aimed to retrospectively evaluate the influence of the initial CT blend sign on short-term outcomes in patients with hypertensive ICH after stereotactic minimally invasive surgery (sMIS). Methods We enrolled 242 patients with spontaneous ICH. The patients were assigned to the blend sign group (91 patients) or non-blend sign (control) group (151 patients) based on the initial CT features. The NIHSS, GCS and mRS were used to assess the effects of sMIS. The rates of severe pulmonary infection and cardiac complications were also compared between the two groups. Results Statistically significant differences in the NIHSS and GCS scores were not observed between the blend sign group and the control group. No significant differences in the proportion of patients with good outcomes during the follow-up period were observed between the two groups. A higher rate of re-haemorrhage was noted in the blend sign group. Significant differences in the rates of severe pulmonary infection and cardiac complications were not observed between the two groups. Conclusions The initial CT blend sign is not associated with poor outcomes in patients with hypertensive ICH after sMIS. ICH patients with the CT blend sign should undergo sMIS if they are suitable candidates for surgery.

Spontaneous intracerebral hemorrhage (ICH), especially related to intraventricular hemorrhage (IVH), is the most devastating type of stroke and is associated with high mortality and morbidity. Optimal management of ICH remains one of the most controversial areas of neurosurgery and no effective treatment exists for ICH. Studies comparing conventional surgical interventions with optimal medical management failed to show significant benefit. Recent exploration of minimally invasive surgery for ICH and IVH including catheter- and mechanical-based approaches has shown great promise. Early phase clinical trials have confirmed the safety and preliminary treatment effect of minimally invasive surgery for ICH and IVH. Pending efficacy data from phase III trials dealing with diverse minimally invasive techniques are likely to shape the treatment of ICH.

Abstract Backgrounds Intracranial post-operative re-haemorrhage is an important complication in patients with hypertensive intracerebral haemorrhage (ICH). The purpose of the present study was to determine the value of the computed tomography (CT) blend sign in predicting post-operative re-haemorrhage in patients with ICH. Methods A total of 126 patients with ICH were included in the present study. All the patients underwent standard stereotactic minimally invasive surgery(MIS) to remove the ICH within 24 h following admission. There were 41 patients with a blend sign on initial CT and 85 patients without a blend sign on the initial CT. Multivariable logistic regression analyses were performed to assess the relationship between the presence of the blend sign on the non-enhanced admission CT scan and post-operative re-haemorrhage. Results Post-operative re-haemorrhage occurred in 24 of the 41 patients with the blend sign, and in 9 of the 85 patients without the blend sign. The incidence of re-haemorrhage was significantly different between the groups. The multivariate logistic regression analysis demonstrated that the initial Glasgow coma scale score (p = 0.002) and blend sign (P