The vesicle trafficking gene, OsRab7, is critical for pollen development and male fertility in cytoplasmic male-sterility rice.

Rice cytoplasmic male sterility (CMS) provides an exceptional model for studying genetic interaction within plant nuclei given its inheritable trait of non-functional male gametophyte. Gaining a comprehensive understanding of the genes and pathways associated with the CMS mechanism is imperative for improving the vigor of hybrid rice agronomically, such as its productivity. Here, we observed a significant decrease in the expression of a gene named OsRab7 in the anther of the CMS line (SJA) compared to the maintainer line (SJB). OsRab7 is responsible for vesicle trafficking and loss function of OsRab7 significantly reduced pollen fertility and setting rate relative to the wild type. Meanwhile, over-expression of OsRab7 enhanced pollen fertility in the SJA line while a decrease in its expression in the SJB line led to the reduced pollen fertility. Premature tapetum and abnormal development of microspores were observed in the rab7 mutant. The expression of critical genes involved in tapetum development (OsMYB103, OsPTC1, OsEAT1 and OsAP25) and pollen development (OsMSP1, OsDTM1 and OsC4) decreased significantly in the anther of rab7 mutant. Reduced activities of the pDR5::GUS marker in the young panicle and anther of the rab7 mutant were also observed. Furthermore, the mRNA levels of genes involved in auxin biosynthesis (YUCCAs), auxin transport (PINs), auxin response factors (ARFs), and members of the IAA family (IAAs) were all downregulated in the rab7 mutant, indicating its impact on auxin signaling and distribution. In summary, these findings underscore the importance of OsRab7 in rice pollen development and its potential link to cytoplasmic male sterility.

Characterizing Negative Online Reviews of Spine Surgeons.

DESIGN: Retrospective review. OBJECTIVE: Characterize negative reviews of spine surgeons in the United States. SUMMARY: Physician rating websites significantly influence the selection of doctors by other patients. Negative experiences are impacted by various factors, both clinical and nonclinical, geography, and practice structure. The purpose of this study was to evaluate and categorize negative reviews of spine surgeons in the United States, with a focus on surgical versus nonsurgical reviewers. METHODS: Spine surgeons were selected from available online professional society membership directories. A search for reviews was performed on Healthgrades.com, Vitals.com, and RateMDs.com for the past 10 years. Free response reviews were coded by complaint, and qualitative analysis was performed. χ 2 and Fisher exact tests were used to compare categorical variables, and multiple comparisons were adjusted with Benjamini-Hochberg correction. A binary logistic regression model was performed for the top three most mentioned nonclinical and clinical complaint labels. A P -value <0.05 was considered statistically significant. RESULTS: A total of 16,695 online reviews were evaluated, including 1690 one-star reviews (10.1%). Among one-star reviews, 64.7% were written by nonsurgical patients and 35.3% by surgical patients. Nonclinical and clinical comments constituted 54.9% and 45.1% of reviews, respectively. Surgeons in the South had more "bedside manner" comments (43.3%, P <0.0001), while Northeast surgeons had more "poor surgical outcome" remarks compared with all other geographic regions (14.4%, P <0.001). Practicing in the South and Northeast were independent predictors of having complaints about "bedside manner" and "poor surgical outcome," respectively. CONCLUSION: Most one-star reviews of spine surgeons were attributed to nonsurgical patients, who tended to be unsatisfied with nonclinical factors, especially "bedside manner." However, there was substantial geographic variation. These results suggest that spine surgeons could benefit from focusing on nonclinical factors (bedside manner), especially among nonoperative patients, and that regional nuances should be considered in delivering spine care. LEVEL OF EVIDENCE: Level- 5.

MicroRNA-29a: a novel target for non-operative management of symptomatic lumbar spinal stenosis.

PURPOSE: Lumbar spinal stenosis (LSS) is the most common reason for spinal surgery in patients over the age of 65, and there are few effective non-surgical treatments. Therefore, the development of novel treatment or preventative modalities to decrease overall cost and morbidity associated with LSS is an urgent matter. The cause of LSS is multifactorial; however, a significant contributor is ligamentum flavum hypertrophy (LFH) which causes mechanical compression of the cauda equina or nerve roots. We assessed the role of a novel target, microRNA-29a (miR-29a), in LFH and investigated the potential for using miR-29a as a therapeutic means to combat LSS. METHODS: Ligamentum flavum (LF) tissue was collected from patients undergoing decompressive surgery for LSS and assessed for levels of miR-29a and pro-fibrotic protein expression. LF cell cultures were then transfected with either miR-29a over-expressor (agonist) or inhibitor (antagonist). The effects of over-expression and under-expression of miR-29a on expression of pro-fibrotic proteins was assessed. RESULTS: We demonstrated that LF at stenotic levels had a loss of miR-29a expression. This was associated with greater LF tissue thickness and higher mRNA levels of collagen I and III. We also demonstrated that miR29-a plays a direct role in the regulation of collagen gene expression in ligamentum flavum. Specifically, agents that increase miR-29a may attenuate LFH, while those that decrease miR-29a promote fibrosis and LFH. CONCLUSION: This study demonstrates that miR-29a may potentially be used to treat LFH and provides groundwork to initiate the development of a therapeutic product for LSS.

OsCBL1 modulates rice nitrogen use efficiency via negative regulation of OsNRT2.2 by OsCCA1.

BACKGROUND: For cereal crop breeding, it is meaningful to improve utilization efficiency (NUE) under low nitrogen (LN) levels while maintaining crop yield. OsCBL1-knockdown (OsCBL1-KD) plants exhibited increased nitrogen accumulation and NUE in the field of low N level. RESULTS: OsCBL1-knockdown (OsCBL1-KD) in rice increased the expression of a nitrate transporter gene OsNRT2.2. In addition, the expression of OsNRT2.2, was suppressed by OsCCA1, a negative regulator, which could directly bind to the MYB-binding elements (EE) in the region of OsNRT2.2 promoter. The OsCCA1 expression was found to be down-regulated in OsCBL1-KD plants. At the low Nitrogen (N) level field, the OsCBL1-KD plants exhibited a substantial accumulation of content and higher NUE, and their actual biomass remained approximately as the same as that of the wild type. CONCLUSION: These results indicated that down-regulation of OsCBL1 expression could upregulate the expression of OsNRT2.2 by suppressing the expression of OsCCA1and then increasing the NUE of OsCBL1-KD plants under low nitrogen availability.

Protective effect of traditional Chinese medicine on non-alcoholic fatty liver disease and liver cancer by targeting ferroptosis.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease with high incidence and is closely related to metabolic syndrome. If not controlled, it may eventually become hepatocellular carcinoma (HCC). Ferroptosis, a non-apoptotic form of programmed cell death (PCD), is closely related to NAFLD and HCC, and the mechanisms of action involved are more complex. Some studies have demonstrated that many drugs inhibit ferroptosis and protect liver steatosis or carcinogenesis. The role of Traditional Chinese Medicine (TCM), especially herbs or herbal extracts, has received increasing attention. However, there are relatively few review articles on the regulation of NAFLD by TCM through ferroptosis pathway. Here, we summarize the TCM intervention mechanism and application affecting NAFLD/NAFLD-HCC via regulation of ferroptosis. This article focuses on the relationship between ferroptosis and NAFLD or NAFLD-HCC and the protective effect of TCM on both by targeting ferroptosis. It not only summarizes the mechanism of early prevention and treatment of NAFLD, but also provides reference ideas for the development of TCM for the treatment of metabolic diseases and liver diseases.

Efficacy and Mechanism of Mallotus furetianus Müll. Arg. Extract on Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is currently the major cause of chronic liver disease globally. To observe the sedative effect of Mallotus furetianus extract (MFE) on NAFLD and the potential molecular mechanism, a high-fat diet (HFD) was used to induce NAFLD in rats for 8 weeks. Rats were orally given MFE (1.7 g/kg, 2.5 g/kg, and 3.3 g/kg) every day. Serum and liver biochemical indexes were detected. 16S rDNA sequencing was performed to test the changes in the gut microbiota. Mass spectrometry was used to analyze the changes in blood and liver metabolites and to perform a joint analysis of differential flora and differential metabolites. The results showed that MFE alleviated liver injury and decreased hepatic lipids content. ELISA analysis certificated that MFE reduced inflammation levels in rats fed with HFD. Compared to HFD rats with a normal diet, MFE significantly changed the overall structure of the intestinal flora and the composition of the intestinal microbes destroyed by HFD. In addition, MFE changes the metabolic levels of lipids and proteins in HFD rats. In conclusion, MFE effectively treated NAFLD and significantly improved the overall structure and intestinal microbial composition of the intestinal microbiota. The abundance of Bacteroides fragilis and Escherichia coli increased significantly in the partridge tea treatment group.

Evaluation and Treatment of Chronic Plantar Fasciitis.

Plantar fasciitis is the most common cause of chronic heel pain in adults, affecting both young active patients and older sedentary individuals. It results from repetitive stress to the plantar fascia at its origin on the medial tubercle of the calcaneus and is often associated with gastrocnemius tightness. The diagnosis can be made clinically with a focused history and physical examination; imaging is reserved for atypical presentations and those that do not respond to initial treatment. The most common presenting symptom is aching plantar heel pain, which is worst with first step in the morning or after periods of rest. Diagnosis is confirmed with point tenderness at the origin of the plantar fascia on the medial tubercle of the calcaneus. Initial treatment consists of activity modification, anti-inflammatory medication, gastrocnemius and plantar fascia stretching, and an in-shoe orthosis that lifts and cushions the heel. These nonoperative treatments lead to complete resolution of pain in 90% of patients but can take 3-6 months. Patients who remain symptomatic despite a 6-month trial of nonoperative therapy may be considered for minimally invasive treatment or surgery. Platelet-rich plasma injections and therapeutic ultrasound are among a number of minimally invasive treatments that stimulate the body's healing response. Corticosteroid injections temporarily relieve pain, but may increase the risk of plantar fascia rupture and fat pad atrophy. Botulinum toxin injections relax the calf muscles, which decreases the stress in the plantar fascia. Operative treatments include gastrocnemius recession and medial head of gastrocnemius release, which decrease the stress on the plantar fascia and partial planter fasciotomy, which stimulates a healing response. LEVEL OF EVIDENCE: Level V, expert opinion.

A new mapping method for quantitative trait loci of silkworm.

BACKGROUND: Silkworm is the basis of sericultural industry and the model organism in insect genetics study. Mapping quantitative trait loci (QTLs) underlying economically important traits of silkworm is of high significance for promoting the silkworm molecular breeding and advancing our knowledge on genetic architecture of the Lepidoptera. Yet, the currently used mapping methods are not well suitable for silkworm, because of ignoring the recombination difference in meiosis between two sexes. RESULTS: A mixed linear model including QTL main effects, epistatic effects, and QTL × sex interaction effects was proposed for mapping QTLs in an F2 population of silkworm. The number and positions of QTLs were determined by F-test and model selection. The Markov chain Monte Carlo (MCMC) algorithm was employed to estimate and test genetic effects of QTLs and QTL × sex interaction effects. The effectiveness of the model and statistical method was validated by a series of simulations. The results indicate that when markers are distributed sparsely on chromosomes, our method will substantially improve estimation accuracy as compared to the normal chiasmate F2 model. We also found that a sample size of hundreds was sufficiently large to unbiasedly estimate all the four types of epistases (i.e., additive-additive, additive-dominance, dominance-additive, and dominance-dominance) when the paired QTLs reside on different chromosomes in silkworm. CONCLUSION: The proposed method could accurately estimate not only the additive, dominance and digenic epistatic effects but also their interaction effects with sex, correcting the potential bias and precision loss in the current QTL mapping practice of silkworm and thus representing an important addition to the arsenal of QTL mapping tools.