MdWRKY31-MdNAC7 regulatory network: orchestrating fruit softening by modulating cell wall-modifying enzyme MdXTH2 in response to ethylene signalling.

Softening in fruit adversely impacts their edible quality and commercial value, leading to substantial economic losses during fruit ripening, long-term storage, long-distance transportation, and marketing. As the apple fruit demonstrates climacteric respiration, its firmness decreases with increasing ethylene release rate during fruit ripening and postharvest storage. However, the molecular mechanisms underlying ethylene-mediated regulation of fruit softening in apple remain poorly understood. In this study, we identified a WRKY transcription factor (TF) MdWRKY31, which is repressed by ethylene treatment. Using transgenic approaches, we found that overexpression of MdWRKY31 delays softening by negatively regulating xyloglucan endotransglucosylase/hydrolases 2 (MdXTH2) expression. Yeast one-hybrid (Y1H), electrophoretic mobility shift (EMSA), and dual-luciferase assays further suggested that MdWRKY31 directly binds to the MdXTH2 promoter via a W-box element and represses its transcription. Transient overexpression of ethylene-induced MdNAC7, a NAC TF, in apple fruit promoted softening by decreasing cellulose content and increasing water-soluble pectin content in fruit. MdNAC7 interacted with MdWRKY31 to form a protein complex, and their interaction decreased the transcriptional repression of MdWRKY31 on MdXTH2. Furthermore, MdNAC7 does not directly regulate MdXTH2 expression, but the protein complex formed with MdWRKY31 hinders MdWRKY31 from binding to the promoter of MdXTH2. Our findings underscore the significance of the regulatory complex NAC7-WRKY31 in ethylene-responsive signalling, connecting the ethylene signal to XTH2 expression to promote fruit softening. This sheds light on the intricate mechanisms governing apple fruit firmness and opens avenues for enhancing fruit quality and reducing economic losses associated with softening.

Does the limb lengthening reduce the incidence of hip dislocation in patients with neurological disorders and insufficient muscle tension who undergoing hip arthroplasty?

Background: The soft-tissue tension is closely associated with postoperative hip dislocation in patients undergoing total hip arthroplasty (THA), especially for those patients with neurological disorders and insufficient muscle tension. The aim of this study is to explore the effect of limb lengthening on the incidence of complications following THA in patients with neurological disorders and insufficient muscle tension. Methods: This retrospective analysis examines individuals with neurological disorders, such as ischemic stroke and poliomyelitis, who underwent primary total hip arthroplasty (THA) at our medical center between January 2015 and April 2021. Demographic and baseline characteristics (such as age, gender, muscle strength) were obtained from medical records. The limb length, offset and the positional parameters of both acetabular and femoral component were measured on pre- and postoperative plain radiograph. The primary outcome was the occurrence of hip dislocation. The secondary outcome included the incidence of other complications and the hip function (determined by Harris score). The correlation between the occurrence of hip dislocation and limb lengthening was analyzed. Results: A total of 258 patients were finally analyzed. The hip dislocations were identified in 35 patients (overall incidence = 13.57%). The incidence of early dislocation was lower in patients whose limb-length discrepancy (LLD) was over 20 mm (incidence = 4.1% for LLD >20 mm, 12.2% for LLD 10 mm-20 mm and 17% for LLD <10 mm). The odds ratio (OR) was 0.206 and 95% confidence interval (CI) was 0.058-0.737 (compared between LLD <10 mm and LLD >20 mm). But the no difference was identified regarding on the incidence of late dislocation among patients with different LLD. Moreover, the overall incidence of other complications was elevated in patients with LLD >20 mm (incidence = 17.58% for LLD >20 mm, 11.11% for LLD 10 mm-20 mm and 3.19% for LLD <10 mm; OR = 6.464, 95% CI = 1.768-23.640). And the Harris scores, which reflected the hip function, was gradually decreased with the increasing in LLD. In terms of the relationship between the offset and dislocation rate, it was found that increased offset discrepancy was associated with decreased dislocation incidence (incidence = 4.71% for offset discrepancy >10 mm, 12.5% for offset discrepancy 5 mm-10 mm and 17.20% for offset discrepancy <5 mm; OR = 0.238, 95% CI = 0.076-0.742). Furthermore, increased offset discrepancy also bring a reduction in late dislocation. The incidences of late dislocation were 0%, 2.5% and 10.8% for offset discrepancy >10 mm, offset discrepancy 5 mm-10 mm and 17.20% for offset discrepancy respectively. Different from that of LDD, the incidences of other complications were similar among patients with different offset discrepancy. Besides, no influence of offset discrepancy on the hip function was identified in this study. Conclusion: Unfortunately, although increasing in limb length could partially reduce early dislocation postoperatively, it could not affect the incidence of late dislocation in those patients with neurological disorders and insufficient muscle tension. Moreover, over limb lengthening was associated with other postoperative complications and worse hip function. Instead, additional offset could reduce the probability of postoperative dislocation, without increasing the incidence of other complications. Therefore, femoral stem with lower cervico-diaphyseal angle (higher offset) should be recommended to patients with neurological disorders who were in high risk of postoperative dislocation. Isolated increasing in limb length should be avoided.

Effectiveness of Needle Aspiration versus Surgical Excision for Symptomatic Synovial Cysts of the Hip: A Single-Center, Retrospective Study.

BACKGROUND This study was performed to evaluate the clinical effectiveness of needle aspiration vs surgical excision for symptomatic synovial cysts of the hip. MATERIAL AND METHODS This retrospective study analyzed the clinical data of patients diagnosed with synovial cysts of the hip and treated in a single-center hospital from January 2012 to April 2022. Patients receiving needle aspiration were assigned to group A and those treated with surgery were assigned to group B. Demographic characteristics, etiology, symptoms, cyst location, postoperative complications and recurrence, Harris Hip Score (HHS) and Visual Analog Scale of Pain (VAS) scores before treatment and at 3, 6, and 12 months after treatment were recorded to assess hip function in both groups. RESULTS This study recruited 44 patients, with 18 patients in group A and 26 in group B, and the 2 arms were well-balanced in terms of baseline patient profiles. Needle aspiration resulted in significantly better pain mitigation for patients at 24 h, 48 h, and 72 h after treatment vs surgical interventions (P<0.05). Needle joint aspiration resulted in significantly better function restoration of the hip joint than surgery at 3 months after treatment, as evidenced by the lower HHS score of 85.31±13.16 in group A vs 78.51±11.66 in group B (P=0.002). Surgery was associated with a significantly lower incidence of disease relapse (0.00%) vs needle aspiration (27.7%) (P=0.004). CONCLUSIONS Needle aspiration in the treatment of symptomatic synovial cysts of the hip causes less damage to the soft tissue and leads to faster recovery in the short term than surgical resection. Surgical resection has a lower recurrence rate and better long-term efficacy.

The indications for core decompression surgery in patients with ARCO stage I-II osteonecrosis of the femoral head: a new, comprehensive prediction system.

BACKGROUND: Core decompression (CD) is considered the most popular treatment method for patients with Association Research Circulation Osseous (ARCO) stage I-II osteonecrosis of the femoral head (ONFH). However, the definitive indication for CD is currently not well established. METHODS: This was a retrospective cohort study. Patients who were diagnosed with ARCO stage I-II ONFH and who underwent CD were included. According to the prognosis, the patients were divided into two groups: collapse of the femoral head after CD and noncollapse of the femoral head. Independent risk factors for the failure of CD treatment were identified. Subsequently, a new scoring system that included all these risk factors was built to help estimate the individual risk of CD failure in patients who were planning to undergo CD. RESULTS: The study included 1537 hips after decompression surgery. The overall failure rate of CD surgery was 52.44%. Seven independent prognostic factors for failed CD surgery were identified, such as male sex (HR = 75.449; 95% confidence interval (CI), 42.863-132.807), Aetiology (Idiopathic HR = 2.762; 95% CI, 2.016-3.788, Steroid-induced HR = 2.543; 95% CI, 1.852-3.685), if the patient had a seated occupation (HR = 3.937; 95% CI, 2.712-5.716), age (HR = 1.045; 95% CI, 1.032-1.058), haemoglobin level (HR = 0.909; 95% CI, 0.897-0.922), disease duration (HR = 1.217; 95% CI, 1.169-1.267) and the combined necrosis angle (HR = 1.025; 95% CI, 1.022-1.028). The final scoring system included these seven risk factors, and the area under the curve of this scoring system was 0.935 (95% confidential interval = 0.922-0.948). CONCLUSION: This new scoring system might provide evidence-based medical proof for determining whether a patient with ARCO stage I - II ONFH might benefit from CD surgery. This scoring system is crucial for making clinical decisions. Consequently, this scoring system is recommended before CD surgery, which could help determine the potential prognosis of patients.

Ethylene inhibits malate accumulation in apple by transcriptional repression of aluminum-activated malate transporter 9 via the WRKY31-ERF72 network.

Malic acid accumulation in the vacuole largely determines acidity and perception of sweetness of apple. It has long been observed that reduction in malate level is associated with increase in ethylene production during the ripening process of climacteric fruits, but the molecular mechanism linking ethylene to malate reduction is unclear. Here, we show that ethylene-modulated WRKY transcription factor 31 (WRKY31)-Ethylene Response Factor 72 (ERF72)-ALUMINUM ACTIVATED MALATE TRANSPORTER 9 (Ma1) network regulates malate accumulation in apple fruit. ERF72 binds to the promoter of ALMT9, a key tonoplast transporter for malate accumulation of apple, transcriptionally repressing ALMT9 expression in response to ethylene. WRKY31 interacts with ERF72, suppressing its transcriptional inhibition activity on ALMT9. In addition, WRKY31 directly binds to the promoters of ERF72 and ALMT9, transcriptionally repressing and activating ERF72 and ALMT9, respectively. The expression of WRKY31 decreases in response to ethylene, lowering the transcription of ALMT9 directly and via its interactions with ERF72. These findings reveal that the regulatory complex WRKY31 forms with ERF72 responds to ethylene, linking the ethylene signal to ALMT9 expression in reducing malate transport into the vacuole during fruit ripening.

Does drainage affect development of heterotopic ossification after total hip arthroplasty?

OBJECTIVE: To investigate the effect of drainage on heterotopic ossification (HO) after total hip arthroplasty (THA) and to evaluate other postoperative complications and joint dysfunction between patients with and without drainage. METHODS: In this retrospective cohort study, the medical records of patients who underwent THA from 2017 to 2019 were reviewed. The patients were divided into a drainage group and non-drainage group. Standard preoperative anteroposterior and lateral radiographs were assessed by senior radiologists for HO analysis. Clinical indicators included the hemoglobin concentration, superficial infection, blood transfusion, hematoma formation, hip range of motion (ROM), erythrocyte sedimentation rate, C-reactive protein concentration, dressing changes, visual analogue scale score, and Harris Hip Score (HHS). RESULTS: The incidence of HO was significantly higher in the drainage than non-drainage group (32.0% vs. 16.3%). The presence of severe HO (Brooker grade III or IV) was also different between the groups. Patients in the non-drainage group had smaller ROM early after surgery, but the final ROM and HHS did not differ significantly between the groups. CONCLUSIONS: The rate and degree of HO after THA were significantly different between patients with and without drainage. There is no added advantage of closed suction drainage over no drainage in primary THA.

KIF4A drives gliomas growth by transcriptional repression of Rac1/Cdc42 to induce cytoskeletal remodeling in glioma cells.

Glioma is one of the most prevalent cancers diseases in the worldwide. Kinesin superfamily protein 4 (KIF4), a KIF member classified in Kinesin 4 has been indicated as a mediator acted in tumorigenesis of human cancer. However, the mechanism of KIF4A on glioma is yet to be investigated. This study aimed to explore the potential function and mechanism of KIF4A in gliomas. We analyzed the KIF4A expression and the prognosis in gliomas patients using The Cancer Genome Atlas (TCGA) databases. KIF4A level in normal human astrocyte cell (NHA) and glioma cell lines were examined by Western blot. We studied the function of KIF4A on proliferation, migration, invasion, cell cycle in glioma cell lines using a series of in vitro and in vivo experiments. Chromatin Immunoprecipitation (ChIP) analysis was applied to searching potential KIF4A related downstream in glioma. We identified the significant up-regulated expression of KIF4A both in glioma tissues and cell. Glioma patients with elevated KIF4A expression have shorter survival. Down-regulation of KIF4A exerted inhibitory effect on cell proliferation, invasion and migration. We crucially identified that KIF4A drives gliomas growth by transcriptional repression of Rac1/Cdc42 to induce cytoskeletal remodeling in glioma cells. Knockdown of KIF4A decreased RohA, Rac1, Cdc42, Pak1 and Pak2 expression level. Our study provided a prospect that KIF4A functions as an oncogene in glioma.

Anthocyanin stability and degradation in plants.

Anthocyanins, a flavonoid group of polyphenolic compounds, have evolved in plants since the land was colonized by plants. These bioactive compounds play critical roles in diverse physiological processes. They are synthesized in the cytosol and transported into the vacuole for storage or to other destinations, where they function as bioactive molecules. The mechanisms of anthocyanin synthesis and transport have been well studied. However, the precise regulation of the mechanisms of anthocyanin degradation remains to be elucidated. In this review, we highlight recent progress in the understanding of the characteristics and functions of anthocyanins and class III peroxidases, as well as of the existing evidence of the effects of class III peroxidases on the degradation of anthocyanins and the possible regulatory mechanisms involved.

The m6A mRNA demethylase FTO in granulosa cells retards FOS-dependent ovarian aging.

Multifunctional N6-methyladenosine (m6A) has been revealed to be an important epigenetic component in various physiological and pathological processes, but its role in female ovarian aging remains unclear. Thus, we demonstrated m6A demethylase FTO downregulation and the ensuing increased m6A in granulosa cells (GCs) of human aged ovaries, while FTO-knockdown GCs showed faster aging-related phenotypes mediated. Using the m6A-RNA-sequence technique (m6A-seq), increased m6A was found in the FOS-mRNA-3'UTR, which is suggested to be an erasing target of FTO that slows the degradation of FOS-mRNA to upregulate FOS expression in GCs, eventually resulting in GC-mediated ovarian aging. FTO acts as a senescence-retarding protein via m6A, and FOS knockdown significantly alleviates the aging of FTO-knockdown GCs. Altogether, the abovementioned results indicate that FTO in GCs retards FOS-dependent ovarian aging, which is a potential diagnostic and therapeutic target against ovarian aging and age-related reproductive diseases.

Apple ethylene response factor MdERF11 confers resistance to fungal pathogen Botryosphaeria dothidea.

Ethylene response factor (ERF) is a plant-specific transcription factor involved in many biological processes including root formation, hypocotyl elongation, fruit ripening, organ senescence and stress responses, as well as fruit quality formation. However, its underlying mechanism in plant pathogen defense against Botryosphaeria dothidea (B. dothidea) remains poorly understood. Here, we isolate MdERF11, an apple nucleus-localized ERF transcription factor, from apple cultivar 'Royal Gala'. qRT-PCR assays show that the expression of MdERF11 is significantly induced in apple fruits after B. dothidea infection. Overexpression of MdERF11 gene in apple calli significantly increases the resistance to B.dothidea infection, while silencing MdERF11 in apple calli results in reduced resistance. Ectopic expression of MdERF11 in Arabidopsis also exhibits enhanced resistance to B. dothidea infection compared to that of wild type. Infections in apple calli and Arabidopsis leaves by B. dothidea respectively cause an increase in endogenous levels of salicylic acid (SA) followed by induction of SA synthesis-related and signaling-related gene expression. Taken together, these findings illustrate a potential mechanism by which MdERF11 elevates plant pathogen defense against B. dothidea by regulating SA synthesis pathway.

Procr-expressing progenitor cells are responsible for murine ovulatory rupture repair of ovarian surface epithelium.

Ovarian surface epithelium (OSE) undergoes recurring ovulatory rupture and repair. The OSE replenishing mechanism post ovulation remains unclear. Here we report that the expression of Protein C Receptor (Procr) marks a progenitor population in adult mice that is responsible for OSE repair post ovulation. Procr+ cells are the major cell source for OSE repair. The mechanism facilitating the rapid re-epithelialization is through the immediate expansion of Procr+ cells upon OSE rupture. Targeted ablation of Procr+ cells impedes the repairing process. Moreover, Procr+ cells displayed robust colony-formation capacity in culture, which we harnessed and established a long-term culture and expansion system of OSE cells. Finally, we show that Procr+ cells and previously reported Lgr5+ cells have distinct lineage tracing behavior in OSE homeostasis. Our study suggests that Procr marks progenitor cells that are critical for OSE ovulatory rupture and homeostasis, providing insight into how adult stem cells respond upon injury.

Increased DKC1 expression in glioma and its significance in tumor cell proliferation, migration and invasion.

The dyskeratosis congenita 1 (DKC1) gene is located on the X chromosome at Xq28. Dyskerin encoded by the DKC1 gene is associated with the formation of certain small RNAs and the telomerase activity. Inherited mutations in DKC1 inactivate the dyskerin and causes dyskeratosis congenital, which is characterized by skin defects, hematopoiesis failure, and increased susceptibility to cancer. DKC1 reportedly up-regulates in several human cancers, including renal cell carcinoma and prostate cancer. Dyskerin is deregulated in B-chronic lymphocytic leukemia and breast carcinomas, but its expression and function in glioma have hardly been investigated. Hence, we were prompted to collect tissue samples and implement cell experiments. Our study reveals that DKC1 expression is significantly increased in the pathological tissues of glioma compared with that in normal tissues. The increased staining of DKC1 is related to the World Health Organization stages of tumors. DKC1 knockdown also significantly inhibits glioma cell growth by altering the expression of cell cycle-relative molecules to arrest at the G1 phase. In the transwell chamber, DKC1 knockdown glioma cells exhibit low motility. Consistent with classic oncogenic pathways, N-cadherin, HIF-1α, and MMP2 expression levels are lower compared with those of the control group. Therefore, DKC1 up-regulation in gliomas is common and necessary for extensive tumor growth. The phenotype of glioma cell lines after DKC1 down-regulation suggests its use as a valuable clinical treatment strategy.

Conservative laparoscopic management of adnexal torsion based on a 17-year follow-up experience.

Laparoscopic unwinding of adnexal torsion has been proposed for decades. However, this technique is still controversial regarding the concern of thromboembolic events. We present two cases of conservative laparoscopic management of adnexal torsion. In the first case, a 16-year-old adolescent with serous cystadenoma was successfully managed by untwisting and cystectomy. We followed up this patient for 17 years with regular re-examinations in our hospital. To the best of our knowledge, this is the longest follow-up reported of this condition. In the second case, a 32-year-old infertile woman who received oocyte retrieval 3 days before being admitted to hospital was referred to hospital with right ovarian torsion. We treated her successfully based on our long-term follow-up experience, and she is now asymptomatic and in her 7th month of pregnancy.

Post-synthetic modification of tryptophan containing peptides via NIS mediation.

A new efficient method was developed to provide modified tryptophan peptides through NIS (N-iodosuccinimide) mediated N2-selective coupling of a Trp unit with 1,2,3-triazoles, of which, the preliminary spectral properties were also studied.