The climate changes promoted the chloroplast genomic evolution of Dendrobium orchids among multiple photosynthetic pathways.

Dendrobium orchids have multiple photosynthetic pathways, which can be used as a model system for studying the evolution of crassulacean acid metabolism (CAM). In this study, based on the results of the net photosynthetic rates (Pn), we classified Dendrobium species into three photosynthetic pathways, then employed and compared their chloroplast genomes. The Dendrobium chloroplast genomes have typical quartile structures, ranging from 150,841-153,038 bp. The apparent differences in GC content, sequence variability, and IR junctions of SSC/IRB junctions (JSBs) were measured within chloroplast genomes among different photosynthetic pathways. The phylogenetic analysis has revealed multiple independent CAM origins among the selected Dendrobium species. After counting insertions and deletions (InDels), we found that the occurrence rates and distribution densities among different photosynthetic pathways were inconsistent. Moreover, the evolution patterns of chloroplast genes in Dendrobium among three photosynthetic pathways were also diversified. Considering the diversified genome structure variations and the evolution patterns of protein-coding genes among Dendrobium species, we proposed that the evolution of the chloroplast genomes was disproportional among different photosynthetic pathways. Furthermore, climatic correlation revealed that temperature and precipitation have influenced the distribution among different photosynthetic pathways and promoted the foundation of CAM pathway in Dendrobium orchids. Based on our study, we provided not only new insights into the CAM evolution of Dendrobium but also provided beneficial genetic data resources for the further systematical study of Dendrobium.

Mitochondrial genome comparison and phylogenetic analysis of Dendrobium (Orchidaceae) based on whole mitogenomes.

BACKGROUND: Mitochondrial genomes are essential for deciphering the unique evolutionary history of seed plants. However, the rules of their extreme variation in genomic size, multi-chromosomal structure, and foreign sequences remain unresolved in most plant lineages, which further hindered the application of mitogenomes in phylogenetic analyses. RESULTS: Here, we took Dendrobium (Orchidaceae) which shows the great divergence of morphology and difficulty in species taxonomy as the study focus. We first de novo assembled two complete mitogenomes of Dendrobium wilsonii and Dendrobium henanense that were 763,005 bp and 807,551 bp long with multichromosomal structures. To understand the evolution of Dendrobium mitogenomes, we compared them with those of four other orchid species. The results showed great variations of repetitive and chloroplast-derived sequences in Dendrobium mitogenomes. Moreover, the intergenic content of Dendrobium mitogenomes has undergone expansion during evolution. We also newly sequenced mitogenomes of 26 Dendrobium species and reconstructed phylogenetic relationships of Dendrobium based on genomic mitochondrial and plastid data. The results indicated that the existence of chloroplast-derived sequences made the mitochondrial phylogeny display partial characteristics of the plastid phylogeny. Additionally, the mitochondrial phylogeny provided new insights into the phylogenetic relationships of Dendrobium species. CONCLUSIONS: Our study revealed the evolution of Dendrobium mitogenomes and the potential of mitogenomes in deciphering phylogenetic relationships at low taxonomic levels.

Effects of geographic isolation on the Bulbophyllum chloroplast genomes.

BACKGROUND: Because chloroplast (cp) genome has more conserved structures than nuclear genome and mitochondrial genome, it is a useful tool in estimating the phylogenetic relationships of plants. With a series of researches for cp genomes, there have been comprehensive understandings about the cp genome features. The genus Bulbophyllum widely distributed in Asia, South America, Australia and other places. Therefore, it is an excellent type genus for studying the effects of geographic isolation. RESULTS: In this study, the cp genomes of nine Bulbophyllum orchids were newly sequenced and assembled using the next-generation sequencing technology. Based on 19 Asian (AN) and eight South American (SA) Bulbophyllum orchids, the cp genome features of AN clade and SA clade were compared. Comparative analysis showed that there were considerable differences in overall cp genome features between two clades in three aspects, including basic cp genome features, SSC/IRB junctions (JSBs) and mutational hotspots. The phylogenetic analysis and divergence time estimation results showed that the AN clade has diverged from the SA clade in the late Oligocene (21.50-30.12 mya). After estimating the occurrence rates of the insertions and deletions (InDels), we found that the change trends of cp genome structures between two clades were different under geographic isolation. Finally, we compared selective pressures on cp genes and found that long-term geographic isolation made AN and SA Bulbophyllum cp genes evolved variably. CONCLUSION: The results revealed that the overall structural characteristics of Bulbophyllum cp genomes diverged during the long-term geographic isolation, and the crassulacean acid metabolism (CAM) pathway may play an important role in the Bulbophyllum species evolution.

Evolution patterns of NBS genes in the genus Dendrobium and NBS-LRR gene expression in D. officinale by salicylic acid treatment.

BACKGROUND: Dendrobium officinale Kimura et Migo, which contains rich polysaccharides, flavonoids and alkaloids, is a Traditional Chinese Medicine (TCM) with important economic benefits, while various pathogens have brought huge losses to its industrialization. NBS gene family is the largest class of plant disease resistance (R) genes, proteins of which are widely distributed in the upstream and downstream of the plant immune systems and are responsible for receiving infection signals and regulating gene expression respectively. It is of great significance for the subsequent disease resistance breeding of D. officinale to identify NBS genes by using the newly published high-quality chromosome-level D. officinale genome. RESULTS: In this study, a total of 655 NBS genes were uncovered from the genomes of D. officinale, D. nobile, D. chrysotoxum, V. planifolia, A. shenzhenica, P. equestris and A. thaliana. The phylogenetic results of CNL-type protein sequences showed that orchid NBS-LRR genes have significantly degenerated on branches a and b. The Dendrobium NBS gene homology analysis showed that the Dendrobium NBS genes have two obvious characteristics: type changing and NB-ARC domain degeneration. Because the NBS-LRR genes have both NB-ARC and LRR domains, 22 D. officinale NBS-LRR genes were used for subsequent analyses, such as gene structures, conserved motifs, cis-elements and functional annotation analyses. All these results suggested that D. officinale NBS-LRR genes take part in the ETI system, plant hormone signal transduction pathway and Ras signaling pathway. Finally, there were 1,677 DEGs identified from the salicylic acid (SA) treatment transcriptome data of D. officinale. Among them, six NBS-LRR genes (Dof013264, Dof020566, Dof019188, Dof019191, Dof020138 and Dof020707) were significantly up-regulated. However, only Dof020138 was closely related to other pathways from the results of WGCNA, such as pathogen identification pathways, MAPK signaling pathways, plant hormone signal transduction pathways, biosynthetic pathways and energy metabolism pathways. CONCLUSION: Our results revealed that the NBS gene degenerations are common in the genus Dendrobium, which is the main reason for the diversity of NBS genes, and the NBS-LRR genes generally take part in D. officinale ETI system and signal transduction pathways. In addition, the D. officinale NBS-LRR gene Dof020138, which may have an important breeding value, is indirectly activated by SA in the ETI system.

Identifying key factors associated with subscapularis tendon tears and developing a risk prediction model to assist diagnosis.

BACKGROUND: There are still some challenges in diagnosing subscapularis (SSC) tendon tears as accurately as posterosuperior rotator cuff tears on MRI. The omission of SSC tendon tear can lead to muscle atrophy, fatty infiltration, and increased tearing accompanied by aggravated shoulder pain and loss of function. An effective non-invasive evaluation tool will be beneficial to early identification and intervention. The study aims to identify sensitive predictors associated with SSC tendon tears and develop a risk prediction model to assist in diagnosis. METHODS: Data on 660 patients who received shoulder arthroscopic surgery with preoperative shoulder MRI were collected retrospectively. Of these, patients with SSC tendon tears were defined as the SSC tear group, and patients with intact SSC tendon were enrolled in the non-SSC tear group. Logistic regression analysis was used to identify the key predictors of SSC tendon tears which were then incorporated into the nomogram. RESULTS: Among 22 candidate factors, five independent factors including coracohumeral distance (CHD, oblique sagittal plane) (OR, 0.75; 95%CI, [0.67-0.84]), fluid accumulation (Y-face) (OR, 2.29; 95%CI, [1.20-4.38]), long head of biceps tendon (LHB) dislocation/subluxation (OR, 3.62; 95%CI, [1.96-6.68]), number of posterosuperior (PS) rotator cuff tears (OR, 5.36; 95%CI, [3.12-9.22]), and MRI diagnosis (based on direct signs) (OR, 1.88; 95%CI, [1.06-3.32]) were identified as key predictors associated with SSC tendon tears. Incorporating these predictors, the nomogram achieved a good C index with a good agreement on the risk estimation of calibration plots. Higher total points of the nomogram were associated with a greater risk of SSC tendon tears. CONCLUSION: When evaluating the severity of SSC tendon injury, the combination of reliable predictors can improve the sensitivity and diagnostic performance of MRI. This model provides an individualized probability of risk prediction, which is convenient for clinicians to identify patients at high risk for SSC tendon tears to avoid missed diagnosis.

Quality of life and treatment satisfaction with pharmacological interventions in Chinese adults with chronic pain due to osteoarthritis.

BACKGROUND: Aim of this multicenter, observational, cross-sectional study was to evaluate health-related quality of life (HRQoL) and treatment satisfaction of current medications in Chinese knee OA patients. METHODS: Brief Pain Inventory (BPI), Treatment Satisfaction Questionnaire (TSQM-1.4), and HRQoL (EQ-5D-5L) were assessed in total of 601 OA of knee patients. Impact on QoL (EQ-5D-5L) and treatment satisfaction (TSQM-1.4) by BPI-Severity score (< 4 and ≥ 4) were presented using mean standard deviations (SDs) and were compared using a t-test. For each of self-assessed health EQ-5D-5L and TSQM, a linear regression model was used to estimate the regression coefficient along with corresponding 95% confidence interval (CI) for BPI-Severity. RESULTS: Mean score of EQ-5D-5L of patients with BPI-Severity ≥4 was significantly lower than those with BPI-Severity < 4. All the scores of TSQM in 4 dimensions were lower in patients with BPI-Severity ≥4 than in those with BPI-Severity < 4. Both HRQoL scores and TSQM scores showed a statistically significant decreasing trend with increasing BPI-Severity pain score. CONCLUSION: Chronic knee OA pain has a significant impact on patients' HRQoL. More severe patients with OA were less satisfied with current treatments.

Efficacy and safety of a single intra-articular injection of 6 ml Hylan G-F 20 compared to placebo in Chinese patients with symptomatic knee osteoarthritis : C-SOUND study, a 26-week multicenter double-blind randomized placebo-controlled trial in China.

BACKGROUND: Single 6 ml Hylan G-F 20 injection, is indicated for knee osteoarthritis patients who have failed to respond to non-pharmacologic therapy and/or simple analgesics. To obtain more thorough understanding of the clinical efficacy and safety, a randomized clinical trial was conducted comparing intra-articular (IA) administration of single 6 ml Hylan G-F 20 injection versus placebo in knee OA patients of Chinese ethnicity. METHODS: This was a randomized, multi-center, double-blind, placebo-controlled clinical trial conducted in 21 centers across China. Four hundred forty adults with knee OA received a single 6 ml Hylan G-F 20 or placebo injection and were evaluated for clinical efficacy and safety outcomes over 26 weeks. Western Ontario and McMaster Universities OA (WOMAC) A1 index, treatment-emergent adverse events (TEAEs) and standard safety parameters were measured at pre-injection, and at weeks 1, 4, 8, 12, 16, 20 and 26 post-injection. RESULTS: Four hundred forty patients (male: 98 [22.3%]; female: 342 [77.7%]) were randomized. The mean age [standard deviation (SD)] was 61.5 (7.9) years. All patients were of East Asian ethnicity. Mean WOMAC A1 score at baseline was 5.3 (1.2) and 5.2 (1.3) in single 6 ml Hylan G-F 20 injection and placebo groups, respectively. Significant reductions of WOMAC A1 score were observed in both treatment groups when compared to baseline at 26 weeks post-injection, with the mean reduction of [standard error (SE)/percentage] -2.146 (0.108)/- 40.5% and - 2.271 (0.110) /- 43.7% in the single 6 ml Hylan G-F 20 injection and the placebo groups, respectively. Additionally, clinically important reductions in pain at 26 weeks was reported in 67.0 and 68.2% in single 6 ml Hylan G-F 20 injection and placebo groups (p = 0.36). Regarding safety, TEAEs were similar between the two treatment groups (hylan G-F 20 single: 61.5%; placebo: 64.5%). CONCLUSIONS: While the magnitude of the effect of a single 6 ml Hylan G-F 20 injection in this study is consistent with previously published literature with respect to the efficacy and safety of the drug, the current study shows a strong IA placebo effect and did not established superiority of single 6 ml Hylan G-F 20 injection over IA placebo in Chinese knee OA patients. TRIAL REGISTRATION: Prospectively registered Jun 16, 2017 at www.clinicaltrials.gov ( NCT03190369 ).

Mutational Biases and GC-Biased Gene Conversion Affect GC Content in the Plastomes of Dendrobium Genus.

The variation of GC content is a key genome feature because it is associated with fundamental elements of genome organization. However, the reason for this variation is still an open question. Different kinds of hypotheses have been proposed to explain the variation of GC content during genome evolution. However, these hypotheses have not been explicitly investigated in whole plastome sequences. Dendrobium is one of the largest genera in the orchid species. Evolutionary studies of the plastomic organization and base composition are limited in this genus. In this study, we obtained the high-quality plastome sequences of D. loddigesii and D. devonianum. The comparison results showed a nearly identical organization in Dendrobium plastomes, indicating that the plastomic organization is highly conserved in Dendrobium genus. Furthermore, the impact of three evolutionary forces-selection, mutational biases, and GC-biased gene conversion (gBGC)-on the variation of GC content in Dendrobium plastomes was evaluated. Our results revealed: (1) consistent GC content evolution trends and mutational biases in single-copy (SC) and inverted repeats (IRs) regions; and (2) that gBGC has influenced the plastome-wide GC content evolution. These results suggest that both mutational biases and gBGC affect GC content in the plastomes of Dendrobium genus.

[Molecular identification of wild populations of Dendrobium officinale based on target region amplification polymorphism].

In this study, TRAP molecular markers were used in identification of wild populations and hybrids of Dendrobium officinale, based on the sequences of genes encoding phosphoenolpyruvate carboxylase (PEPC), UDP-glucose pyrophosphorylase (UGP) and phenylalanine ammonia-lyase (PAL). Seven polymorphic target region amplification polymorphism (TRAP) primers were selected from 54 primer combinations and used in the identification of wild populations. Moreover, hybrids had female polymorphic bands, male polymorphic bands and heterozygous bands, which suggest that seven TRAP markers are able to identify the hybrids from their parents. Furthermore, the UPGMA dendrogram revealed that when sample from Guangnan in Yunnan province was used as one parent, reciprocal hybrids grouped with them in first, and then grouped with the other parent. The results indicated that the hybrids were closer to D. officinale from Guangnan population. This study identified the wild populations and hybrids of D. officinale by TRAP molecular markers, which is useful in selection of good varieties for artificial cultivation and early identification of hybrids. The study provides a method in the control of stability of germplasm and quality of D. officinale.

[Evaluation of genetic diversity and population structure of Bletilla striata based on SRAP markers].

Bletilla striata has been used as traditional Chinese medicine for several centuries. In recent years, the quality and quantity of wild B. striata plants have declined sharply due to habitat deterioration and human over-exploitation. Therefore, it is of great urgency to evaluate and protect B. striata wild plant resource. In this study, sequence-related amplified polymorphism (SRAP) markers were applied to assess the level and pattern of genetic diversity in twelve populations of B. striata. The results showed a high level of genetic diversity (PPB = 90.48%, H = 0.349 4, I = 0.509 6) and moderate genetic differentiation among populations (G(st) = 0.260 9). Based on the unweighted pair-group method with arithmetic average (UPGMA), twelve populations gathered in three clusters. The cluster 1 included four populations. There are Nanjing, Zhenjiang, Xuancheng and Hangzhou. The seven populations which come from Hubei Province, Hunan Province, Jiangxi Province and Guizhou Province belonged to the cluster 2. The cluster 3 only contained Wenshan population. Moreover, Mantel test revealed significant positive correlation between genetic distances and geographic distances (r = 0.632 9; P < 0.000 1). According to the results, we proposed a series of conservation consideration for B. striata.

Different evolutionary processes in shaping the genetic composition of Dendrobium nobile in southwest China.

Knowledge of population genetic structure and intrapopulation genetic variation is important for understanding population dynamics and evolutionary processes. Dendrobium nobile is an endangered traditional Chinese tonic medicine. In order to analyze the population differentiation and genetic diversity in D. nobile and propose proper conservation measurements, we genotyped 102 individual plants from 7 natural populations distributed across southwest China at 9 microsatellite loci. Seven pairs of genomic SSR primers were newly designed, and two pairs were chosen from the EST-SSRs. According to the results, the genetic process of D. nobile on Hainan Island and the Chinese mainland might be affected by different evolutionary processes, the genetic drift caused by founder effect has played an important role in shaping the genetic constitution of the Island population. The population of D. nobile in Hainan Island was highly differentiated and displayed low levels of genetic diversity. For the conservation management plans of D. nobile, we propose that individuals in Hainan Island with rare alleles need to be conserved with top priority, and those individuals with rare alleles and the most common alleles also should be concerned. The seven new microsatellite loci may be informative for further evaluation and conservation of the genetic diversity of D. nobile.

[Applylication of new type combined fragments: nrDNA ITS+ nad 1-intron 2 for identification of Dendrobium species of Fengdous].

In this study, 17 kinds of Dendrobium species of Fengdous including 39 individuals were collected from 4 provinces. Mitochondrial gene sequences co I, nad 5, nad 1-intron 2 and chloroplast gene sequences rbcL, matK amd psbA-trnH were amplified from these materials, as well as nrDNA ITS. Furthermore, suitable sequences for identification of Dendrobium species of Fengdous were screened by K-2-P and P-distance. The results showed that during the mentioned 7 sequences, nrDNA ITS, nad 1-intron 2 and psbA-trnH which had a high degree of variability could be used to identify Dendrobium species of Fengdous. However, single fragment could not be used to distinguish D. moniliforme and D. huoshanense. Moreover, compared to other combined fragments, new type combined fragments nrDNA ITS+nad 1-intron 2 was more effective in identifying the original plants of Dendrobium species and could be used to identify D. huoshanense and D. moniliforme. Besides, according to the UPGMA tree constructed with nrDNA ITS+nad 1-intron 2, 3 inspected Dendrobium plants were identified as D. huoshanense, D. moniliforme and D. officinale, respectively. This study identified Dendrobium species of Fengdous by combined fragments nrDNA ITS+nad 1-intron 2 for the first time, which provided a more effective basis for identification of Dendrobium species. And this study will be helpful for regulating the market of Fengdous.

[Value of predicting preoperative risk in orthopedic surgery by using POSSUM].

OBJECTIVE: To assess the use of Physical and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM) scoring system in predicting outcomes of patients undergoing orthopedic surgery and provide guidance for operation treatment decisions. METHODS: From April 2009 to September 2010, a total of 779 cases went operation in Beijing Hospital were collected.They were divided into two groups according to the presence or absence of complications.The patients' postoperative complications were predicted by POSSUM and compared to the actual morbidity to verify the effectiveness of the equation.Logistic regression was taken to make appropriate improvements for the POSSUM equation.ROC curve was drawn to describe the compliance of the original and new equations. RESULTS: In the 779 cases, the morbidity predicted by POSSUM is 212 cases while the actual morbidity is 65 cases.Of all risk factors, echocardiography ejection fraction showed a close relationship with postoperative complications (P<0.01). In the original equation, actual complication group compared with non-complication group, the difference was statistically significant (P<0.01). In the modified equation, complication group compared with non-complication group, the difference was statistically significant (P<0.01). Compared with the original one , the modified POSSUM had better predictive value on postoperative morbidity, and the comparison of AUC between the two groups was statistically significant ((0.67 ± 0.12) vs (0.75 ± 0.08), P<0.01). CONCLUSION: POSSUM over predicted morbidity of patients undergoing orthopedic surgery, it can be more accurate when modified appropriately.

Association between niacin intake and knee osteoarthritis pain and function: a longitudinal cohort study.

BACKGROUND: This research investigates the relationship between niacin intake and knee osteoarthritis (OA) severity, focusing on pain and functional ability due to niacin's role as a NAD(P)+ precursor, promoting cellular energy, and offering anti-inflammatory, analgesic, and antioxidant effects. METHODS: The population-based Osteoarthritis Initiative (OAI) cohort with radiographically confirmed knee OA was analyzed through a Food Frequency Questionnaire determining niacin intake and scores from the Knee Injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), using generalized additive mixed models. RESULTS: A significant correlation was pinpointed in 2375 OA patients (1001 men and 1374 women; 55.96% aged between 45 and 65 and 44.04% aged ≥65) between niacin intake and reduced knee pain and functional degrees after a 48-month follow-up, evident in improved KOOS and WOMAC scores (P < 0.05). The fully adjusted models estimated a decrease of 0.26 points for every additional 1 unit of Ln-niacin intake of daily niacin intake on the WOMAC pain subscale, 0.83 points on the WOMAC function subscale, and an increase of 1.71 and 1.58 on the KOOS pain and quality of life score. Strikingly, subgroups including middle-aged individuals, women, white race, obese individuals, and those with specific dietary habits showed a more substantial improvement with increased niacin. CONCLUSION: The association between increased niacin intake and reduced pain and function scores, as well improved quality of life in knee OA patients, is significant. Certain cohorts, according to a stratified analysis, could see more considerable benefits with increased niacin consumption. HIGHLIGHTS: • Increased niacin intake is linked to reduced knee pain and better function in OA patients. • Specific subgroups, such as middle-aged individuals, women, and those with certain dietary habits, benefit more from increased niacin consumption. • Niacin shows promise for enhancing the quality of life in knee OA patients by reducing pain and improving function.

The association of urinary heavy metal exposure with frailty susceptibility and mortality in middle-aged and older adults: a population-based study.

Heavy metals' presence as environmental pollutants has a close link to adverse health effects. Frailty, a clinical syndrome hallmarked by elevated vulnerability to stressors, presents a substantial challenge in healthcare. However, the association between exposure to heavy metals and frailty largely remains unexplored. Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2003-2018 and correlated with the U.S. National Death Index (NDI) from 2019, we investigated mortality outcomes. Logistic regression, Cox regression, Kaplan-Meier survival curves, weighted quantile-sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were employed to assess the association between heavy metal exposure and frailty incidence and mortality in the frail population. Eight metals were measured in urine using inductively coupled plasma mass spectrometry with values adjusted for urinary creatinine, which was used to reflect heavy metal exposure. The cohort incorporated 5370 female participants aged 45 and above, with 1518 diagnosed with frailty. The findings indicated a substantial correlation between exposure to specific heavy metals, namely tungsten (odds ratio [OR]: 1.94, 95% confidence interval [CI]: 1.31-2.89), cobalt (OR: 1.64, 95% CI: 1.40-1.93), cadmium (OR: 1.93, 95% CI: 1.52-2.43), and uranium (OR: 7.36, 95% CI: 1.53-35.28), and an elevated risk of frailty. WQS and BKMR regression models identified cadmium, cobalt, and tungsten as main contributors to frailty. Cox regression analysis, after adjustment for covariates, suggested that the higher the exposure levels to cadmium and lead, the higher the risk of death in frail patients, with associated hazard ratios (HR) of 95% CI: 1.96 (1.53, 2.52) and 1.30 (1.13, 1.49), respectively. Our study revealed a significant positive correlation between exposure to heavy metal mixtures and frailty onset in middle-aged and older adults, along with increased mortality in frail patients. Cobalt, cadmium, and tungsten emerged as prominent contributors to frailty, with cobalt and cadmium directly impacting the long-term life expectancy of frail patients.

Randomized, double-blind, placebo-controlled, multicenter study to evaluate efficacy and safety of the denosumab biosimilar MW031 in Chinese postmenopausal women with osteoporosis.

BACKGROUND: This study aimed to assess the efficacy and safety of MW031 in Chinese postmenopausal women with osteoporosis. PATIENTS AND METHODS: In this randomized, double-blind, placebo-controlled, multicenter clinical trial, 448 postmenopausal women with osteoporosis were randomized 3:1 to receive MW031 and placebo for 12 months. The primary efficacy endpoint was the percentage change from baseline in BMD at lumbar spine in month 12. The safety and immunogenicity profiles were also included. RESULTS: Of 448 randomized patients, 421 completed the study (MW031, n = 322; placebo, n = 99).After 12 months of MW031 treatment, BMD increased by 5.80% at lumbar spine,3.65% at total hip, and 2.93% at femoral neck. The model-adjusted difference was 3.86% (P<0.0001), 2.34% (P<0.0001), and 1.05% (p = 0.08) compared with placebo group, respectively. For the bone turnover markers, serum CTX level in MW031 group decreased to the maximum difference in month 1 (-71.71%, 95% CI: -77.83%, -65.60%, P<0.0001) compared with the placebo group. The safety analysis showed no significant differences in the proportion of patients reporting any adverse events between the two groups. CONCLUSION: This study demonstrated that MW031 safely and effectively increased BMD and rapidly decreased the level of bone resorption marker in Chinese postmenopausal women with osteoporosis. TRIAL REGISTRATION: NCT05215977 (ClinicalTrials.gov.).

Rhizocompetence and antagonistic activity towards genetically diverse Ralstonia solanacearum strains--an improved strategy for selecting biocontrol agents.

Bacterial wilt caused by Ralstonia solanacearum is a serious threat for agricultural production in China. Eight soil bacterial isolates with activity against R. solanacearum TM15 (biovar 3) were tested in this study for their in vitro activity towards ten genetically diverse R. solanacearum isolates from China. The results indicated that each antagonist showed remarkable differences in its ability to in vitro antagonize the ten different R. solanacearum strains. Strain XY21 (based on 16S rRNA gene sequencing affiliated to Serratia) was selected for further studies based on its in vitro antagonistic activity and its excellent rhizocompetence on tomato plants. Under greenhouse conditions XY21 mediated biocontrol of tomato wilt caused by seven different R. solanacearum strains ranged from 19 to 70 %. The establishment of XY21 and its effects on the bacterial community in the tomato rhizosphere were monitored by denaturing gradient gel electrophoresis of 16S rRNA gene fragments PCR-amplified from total community DNA. A positive correlation of the in vitro antagonistic activities of XY21 and the actual biocontrol efficacies towards seven genetically different R. solanacearum strains was found and further confirmed by the efficacy of XY21 in controlling bacterial wilt under field conditions.

Short-term alendronate treatment does not maintain a residual effect on spinal fusion with interbody devices and bone graft after treatment withdrawal: an experimental study on spinal fusion in pigs.

PURPOSE: Whether alendronate treatment has a residual effect on bone ingrowth into porous biomaterial in humans or experimental animals after treatment withdrawal is still unknown. The purpose of this study was to investigate bone ingrowth into porous tantalum and carbon fiber interbody implants after discontinuing alendronate treatment in experimental spinal fusion in pigs. METHODS: Twenty-four pigs were randomly divided into two groups of each 12 pigs. The pigs underwent anterior intervertebral lumbar arthrodeses at L2-3, L4-5 and L6-7. Each level was randomly allocated to one of the three implants: a porous tantalum ring with pedicle screw fixation, a porous tantalum ring or a carbon fiber cage with anterior staple fixation. The central hole of implants was packed with an autograft. Alendronate was given orally for the first 3 months to one of the two groups. The pigs were observed for 6 months postoperatively. Histology and micro-CT scans were done at the endpoint. RESULTS: The spinal fusion rates of each implant showed no differences between two treatment groups. Furthermore, no differences were found between two groups as for bone ingrowth into the central holes of implants and bone-implant interface in each implant, or as for the pores of tantalum implants. Trabecular bone microarchitecture in the central hole of the carbon fiber cage did not differ between two treatment groups. CONCLUSION: The application of ALN, with a dose equivalent to that given to humans during the first 3 months after surgery, does not maintain a residual effect on spinal fusion with porous tantalum ring and autograft after treatment withdrawal in a porcine ALIF model.

The influence of zinc and iron intake on osteoarthritis patients' subchondral sclerosis progression: A prospective observational study using data from the osteoarthritis Initiative.

Objective: The purpose of this investigation was to elucidate the relationship between the zinc and iron intake and the advancement of subchondral sclerosis among patients with osteoarthritis (OA). The goal was to establish personalized, nutritionally-informed strategies designed to retard the progression of subchondral sclerosis and conserve joint structure. Methods: For the purposes of this research, we derived data from the Bone Ancillary Study (BAS), a constituent study of the Osteoarthritis Initiative (OAI). The intake of zinc and iron was evaluated via a food frequency questionnaire. Magnetic Resonance Imaging trabecular morphometry was employed to ascertain the microarchitecture of the subchondral bone. For the analysis of collected data, we employed logistic regression along with generalized additive models (GAMs). Results: The participant cohort was comprised of 474 OA patients (216 females, 258 males, mean [SD] age 64.1[9.2]). Notably, an increment in zinc consumption was linked with a significantly reduced likelihood of deterioration in Tb.N (OR = 0.967, 95 % CI, 0.939-0.996, P-value = 0.026), Tb.Th (OR = 0.958, 95 % CI, 0.929-0.989, P-value = 0.008), and Tb.Sp (OR = 0.967, 95 % CI, 0.939-0.996, P-value = 0.013). An elevation in iron intake seemed to enhance the risk of subchondral sclerosis, as indicated by the GAM. Subgroup analysis revealed an interaction between the effectiveness of zinc intake and factors such as gender, age, radiographic severity, and macronutrient consumption. An increased intake of calcium amplified the beneficial impact of zinc on subchondral sclerosis. Conclusions: Our findings indicate a positive association between elevated zinc intake and a slowdown in the progression of subchondral sclerosis in OA patients, notably among females, middle-aged individuals, and those with higher calcium and magnesium intake. Conversely, a higher iron intake might intensify subchondral sclerosis. These results suggest that personalized, diet-based interventions focusing on zinc consumption, in tandem with adequate calcium intake, could potentially decelerate the progression of subchondral sclerosis in individuals afflicted with OA.

Association between dietary folate intake and bone mineral density in a diverse population: a cross-sectional study.

BACKGROUND: Osteoporosis is a major public health problem, yet the association between dietary folate intake and bone health has been rarely studied. This study aimed to investigate the relationship between dietary folate intake and bone mineral density (BMD) in the general population of the USA. METHODS: Utilizing data from the National Health and Nutrition Examination Survey, dietary folate intake was gauged through 24-h dietary recall and BMD was determined via dual-energy X-ray absorptiometry. Multivariate linear regression models and generalized additive models were employed for correlation analysis. RESULTS: The study incorporated 9839 participants (48.88% males, aged 20-85 years, mean age: 47.62 ± 16.22). The average dietary folate intake stood at 401.1 ± 207.9 µg/day. And the average total femur, femoral neck, trochanter, intertrochanter, and lumbar BMD were 0.98 ± 0.16 g/cm2, 0.84 ± 0.15 g/cm2, 0.73 ± 0.13 g/cm2, 1.16 ± 0.19 g/cm2, and 1.03 ± 0.15 g/cm2, respectively. The higher quartiles of dietary folate intake directly correlated with increased total femoral, femoral neck, intertrochanteric, and lumbar BMD (P for trend = 0.003, 0.016, < 0.001, and 0.033, respectively). A consistent positive association between folate intake and BMD across age groups was observed, with significant findings for individuals over 80 years and non-Hispanic whites. Physical activity level and serum 25-hydroxyvitamin D levels influenced the association, with an optimal daily folate intake of 528-569 µg recommended for postmenopausal women. CONCLUSION: In summary, our study reveals a significant positive association between dietary folate intake and BMD, across different age groups and particularly among individuals over 80 years old. Non-Hispanic whites benefit the most from increased folate intake. Physical activity level and serum 25-hydroxyvitamin D levels interact with this association. Screening and early intervention for osteoporosis may be essential for individuals with low dietary folate intake.