Aspartyl proteases identified as candidate genes of a fiber length QTL, qFLD05, that regulates fiber length in cotton (Gossypium hirsutum L.).

KEY MESSAGE: GhAP genes were identified as the candidates involved in cotton fiber length under the scope of fine mapping a stable fiber length QTL, qFLD05. Moreover, the transcription factor GhWRKY40 positively regulated GhAP3 to decrease fiber length. Fiber length (FL) is an economically important fiber quality trait. Although several genes controlling cotton fiber development have been identified, our understanding of this process remains limited. In this study, an FL QTL (qFLD05) was fine-mapped to a 216.9-kb interval using a secondary F2:3 population derived from the upland hybrid cultivar Ji1518. This mapped genomic segment included 15 coding genes, four of which were annotated as aspartyl proteases (GhAP1-GhAP4). GhAPs were identified as candidates for qFLD05 as the sequence variations in GhAPs were associated with FL deviations in the mapping population, and functional validation of GhAP3 and GhAP4 indicated a longer FL following decreases in their expression levels through virus-induced gene silencing (VIGS). Subsequently, the potential involvement of GhWRKY40 in the regulatory network was revealed: GhWRKY40 positively regulated GhAP3's expression according to transcriptional profiling, VIGS, yeast one-hybrid assays and dual-luciferase experiments. Furthermore, alterations in the expression of the eight previously reported cotton FL-responsive genes from the above three VIGS lines (GhAP3, GhAP4 and GhWRKY40) implied that MYB5_A12 was involved in the GhWRKY40-GhAP network. In short, we unveiled the unprecedented FL regulation roles of GhAPs in cotton, which was possibly further regulated by GhWRKY40. These findings will reveal the genetic basis of FL development associated with qFLD05 and be beneficial for the marker-assisted selection of long-staple cotton.

Overcoming research challenges: In vitro cultivation of Ameson portunus (Phylum Microsporidia).

Ameson portunus is an intracellular pathogen that infects marine crabs Portunus trituberculatus and Scylla paramamosain, causing significant economic losses. However, research into this important parasite has been limited due to the absence of an in vitro culture system. To address this challenge, we developed an in vitro cultivation model of A. portunus using RK13 cell line in this study. The fluorescent labeling assay indicated a high infection rate (∼60 %) on the first day post-infection and quantitative PCR (qPCR) detection demonstrated successful infection as early as six hours post-inoculation. Fluorescence in situ hybridization (FISH) and qPCR were used for the detection of A. portunus infected cells. The FISH probe we designed allowed detection of A. portunus in infected cells and qPCR assay provided accurate quantification of A. portunus in the samples. Transmission electron microscopy (TEM) images revealed that A. portunus could complete its entire life cycle and produce mature spores in RK13 cells. Additionally, we have identified novel life cycle characteristics during the development of A. portunus in RK 13 cells using TEM. These findings contribute to our understanding of new life cycle pathways of A. portunus. The establishment of an in vitro culture model for A. portunus is critical as it provides a valuable tool for understanding the molecular and immunological events that occur during infection. Furthermore, it will facilitate the development of effective treatment strategies for this intracellular pathogen.

Generalized central slice theorem perspective on Fourier-transform spectral imaging at a sub-Nyquist sampling rate.

Fourier-transform spectral imaging captures frequency-resolved images with high spectral resolution, broad spectral range, high photon flux, and low stray light. In this technique, spectral information is resolved by taking Fourier transformation of the interference signals of two copies of the incident light at different time delays. The time delay should be scanned at a high sampling rate beyond the Nyquist limit to avoid aliasing, at the price of low measurement efficiency and stringent requirements on motion control for time delay scan. Here we propose, what we believe to be, a new perspective on Fourier-transform spectral imaging based on a generalized central slice theorem analogous to computerized tomography, using an angularly dispersive optics decouples measurements of the spectral envelope and the central frequency. Thus, as the central frequency is directly determined by the angular dispersion, the smooth spectral-spatial intensity envelope is reconstructed from interferograms measured at a sub-Nyquist time delay sampling rate. This perspective enables high-efficiency hyperspectral imaging and even spatiotemporal optical field characterization of femtosecond laser pulses without a loss of spectral and spatial resolutions.

Genetic mapping, transcriptomic sequencing and metabolic profiling indicated a glutathione S-transferase is responsible for the red-spot-petals in Gossypium arboreum.

KEY MESSAGE: A GST for red-spot-petals in Gossypium arboreum was identified as the candidate under the scope of multi-omics approaches. Colored petal spots are correlated with insect pollination efficiency in Gossypium species. However, molecular mechanisms concerning the formation of red spots on Gossypium arboreum flowers remain elusive. In the current study, the Shixiya1-R (SxyR, with red spots) × Shixiya1-W (SxyW, without red spots) segregating population was utilized to determine that the red-spot-petal phenotype was levered by a single dominant locus. This phenotype was expectedly related to the anthocyanin metabolites, wherein the cyanidin and delphinidin derivatives constituted the major partition. Subsequently, this dominant locus was narrowed to a 3.27 Mb range on chromosome 7 by genomic resequencing from the two parents and the two segregated progeny bulks that have spotted petals or not. Furthermore, differential expressed genes generated from the two bulks at either of three sequential flower developmental stages that spanning the spot formation were intersected with the annotated ones that allocated to the 3.27 Mb interval, which returned eight genes. A glutathione S-transferase-coding gene (Gar07G08900) out of the eight was the only one that exhibited simultaneously differential expression among all three developmental stages, and it was therefore considered to be the probable candidate. Finally, functional validation upon this candidate was achieved by the appearance of scattered petal spots with inhibited expression of Gar07G08900. In conclusion, the current report identified a key gene for the red spotted petal in G. arboreum under the scope of multi-omics approaches, such efforts and embedded molecular resources would benefit future applications underlying the flower color trait in cotton.

Unrelated Donor Peripheral Blood Stem Cell Transplantation for Patients with ß-Thalassemia Major Based on a Novel Conditioning Regimen.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only available curative treatment for patients with ß-thalassemia major (ß-TM). However, the problem of finding a suitable sibling donor with well-matched human leukocyte antigens is still a major obstacle to curing these patients. With the progress in high-resolution HLA typing technology and supportive care, outcomes after allogeneic HSCT from an HLA well-matched unrelated donor (UD) now approach those of well-matched sibling donors. However, UD HSCT is hampered by an increased risk of graft-versus-host disease and transplant-related mortality. Here we report the outcome of transplantation in patients with ß-TM using a novel WZ-14-TM transplant protocol, based on cyclophosphamide, intravenous busulfan, fludarabine, and antithymocyte globulin, in our center. Forty-eight patients between 2 and 11 years of age with ß-TM received HLA well-matched UD peripheral blood stem cell transplantation following the WZ-14-TM protocol. All of the transplanted patients achieved donor engraftment. The incidences of grade II to IV acute and chronic graft-versus-host disease were 8.3% and 8.3%, respectively. The overall survival and thalassemia-free survival rates were both 100%. This encouraging result suggests that the WZ-14-TM protocol is a feasible and safe conditioning regime for patients with ß-TM undergoing UD HSCT.

Mean platelet volume predicts prognosis in patients with diffuse large B-cell lymphoma.

To determine the prognostic value of baseline mean platelet volume (MPV) in diffuse large B-cell lymphoma (DLBCL) patients. We retrospectively analyzed 161 DLBCL patients who received R-CHOP chemotherapy. The associations between MPV and clinicopathological factors were assessed. A low MPV (MPV ≤ 9.1 fl, cut-off was calculated by receiver operating characteristics) was not associated with any other clinicopathological factors. Patients with MPV ≤ 9.1 fl experienced a shorter progression-free survival (PFS) (2-year PFS rate, 60.6% vs 84.0%, P = 0.003) and overall survival (OS) (2-year OS rate, 70.4% vs 87.9%, P = 0.030), compared with those with MPV > 9.1 fl. The multivariate analysis demonstrated that MPV ≤ 9.1 fl was an independent prognostic factor of OS (Hazard Ratio [HR] = 0.588, P = 0.045) and PFS (HR = 0.456, P = 0.010). Therefore, we demonstrated that low baseline MPV is an independent prognostic marker of poor outcome in patients with DLBCL.

Down-regulation of CD19 expression inhibits proliferation, adhesion, migration and invasion and promotes apoptosis and the efficacy of chemotherapeutic agents and imatinib in SUP-B15 cells.

The survival rate of childhood acute lymphoblastic leukemia (ALL) has increased while that of Philadelphia-positive (Ph+) ALL remains low. CD19 is a B-cell specific molecule related to the survival and proliferation of normal B cells. However, there is little information available on the effects of CD19 on the biological behavior of Ph+ ALL cells. In this study, we explored a lentiviral vector-mediated short hairpin RNA (shRNA) expression vector to stably reduce CD19 expression in Ph+ ALL cell line SUP-B15 cells and investigated the effects of CD19 downregulation on cell proliferation, apoptosis, drug sensitivity, cell adhesion, cell migration and cell invasion in vitro. CD19 mRNA and protein expression levels were inhibited significantly by CD19 shRNA. Down-regulation of CD19 could inhibit cell proliferation, adhesion, migration and invasion, and increase cell apoptosis and the efficacy of chemotherapeutic agents and imatinib in SUP-B15 cells. Moreover, we found that down-regulation of CD19 expression inhibits cell proliferation and induces apoptosis in SUP-B15 cells in a p53-dependent manner. Taken together, our results suggest that lentiviral vector-mediated RNA interference of CD19 gene may be a promising strategy in the treatment of Ph+ ALL.

Peripheral blood lymphocyte/monocyte ratio following completion of first-line therapy predicts early relapse in patients with diffuse large B cell lymphoma.

To investigate whether the post-therapy lymphocyte/monocyte ratio (ALC/AMC ratio or LMR) predicts early relapse in patients with diffuse large B cell lymphoma (DLBCL), we enrolled 125 consecutive patients with DLBCL and followed up from 2005 to 2015 in our hospital. The LMR was measured following completion of first-line therapy. We found that the LMR following completion therapy was a strong predictor of early relapse, which is less than 12 months after diagnosis. A low LMR was significantly associated with early relapse in both univariate [odds ratio (OR) = 8.8; P = 0.006] and multivariate analysis (OR = 8.951; P = 0.011). The low-LMR group (<2.9) had poorer outcomes than the high-LMR group (≥2.9), with a lower 2-year progression-free survival rate (78.9 versus 97.1 %, P = 0.002) and 2-year OS rate (82.5 versus 98.5 %, P = 0.002). This study suggests that a lower LMR following completion of first-line therapy can be used as a marker to predict early relapse in patients with DLBCL.

Pharmacokinetics and Bioequivalence of Amlodipine Besylate Tablet in Healthy Chinese Volunteers Under Fasting and Fed Conditions.

The purpose of this study was to compare the blood concentration and pharmacokinetic (PK) parameters of 2 formulations under fasting and ed conditions in healthy Chinese volunteers and to evaluate whether the 2 preparations were bioequivalent. This trial screened 170 subjects. Thirteen subjects were assigned to the fasting trial and 18 subjects to the fed trial; 1 subject in the fed trial group was automatically withdrawn for personal reasons. Two cycles had a 14-day washout period. This clinical study was a bioequivalence study, with PK parameters as end point indicators. The bioequivalence PK parameters were the maximal concentration (Cmax ), area under the blood drug concentration-time curve from 0 to 72 hours (AUC0-72 h ), and the time to peak plasma concentration (tmax ) which were determined in human plasma by the liquid chromatography-tandem mass spectrometry method, and nonatrioventricular model analysis was used to determine Cmax , AUC0-72 h , tmax , and other PK parameters. The incidence of adverse events was calculated on the basis of System Organ Classification and Preferred Terms. The results showed that the amlodipine besylate tablets met the equivalence range requirements of bioequivalence in the guidelines for human bioavailability and bioequivalence testing under fasting and fed conditions, compared to the fasting test; the tmax of the fed test was almost unchanged; and the Cmax and AUC0-72 h showed no difference between fasting and fed conditions. It was confirmed that both formulations were well tolerated, and no new safety signals were observed.

Evaluation of Ornidazole Tablets Bioequivalence in Chinese Healthy Participants Under Fasted and Fed Conditions Using Pharmacokinetic Parameters.

BACKGROUND AND OBJECTIVE: Ornidazole, the third generation of nitroimidazole derivatives after metronidazole and tinidazole, it exerts both bactericidal and antiprotozoal effects. The purpose of this study was to evaluate the pharmacokinetic and bioequivalence of two ornidazole tablets manufactured by two different manufacturers based on their pharmacokinetic parameters. PATIENTS AND METHODS: Fasted and fed healthy Chinese volunteers participated in a randomized sequence, single-dose, open-label, two-period crossover trial. There were 24 participants in both the fed study and the fasted study. Following a 7-day washout period before receiving the alternative formulation, eligible research participants were randomly assigned (1:1) to receive a single dosage of either the reference formulation or the test formulation. Following tablet administration, plasma samples were obtained over 72 h and analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS) to evaluate ornidazole contents. maximum plasma concentration (Cmax), time to Cmax (Tmax), the area under the curve (AUC) from t = 0 to infinity (AUC0-∞), AUC from t = 0 to the last quantifiable concentration (AUC0-t), half-life (t1/2), and terminal elimination rate constant (z) were evaluated as pharmacokinetic (PK) parameters. The safety evaluation involved adverse events (AEs) incidence and alterations in laboratory tests (hepatic function, blood biochemistry, hematology, and urinalysis) or vital signs (temperature, pulse, and blood pressure). RESULTS: For the bioequivalence assessment in the fast trial, the prime PK parameters comparison between the reference and test formulation revealed that the GMR (90% CI) values for AUC0-t, Cmax, and AUC0-∞ were 100.97% (99.12-102.85%), 99.88% (90.63-110.08%), and 101.12% (99.17-103.11%), respectively. For the bioequivalence assessment in the fed trial, the key PK parameters comparison between the reference and test formulations revealed that the GMR (90% CI) values for AUC0-t, Cmax, and AUC0-∞ were 103.00% (100.94-105.11%), 101.90% (99.63-104.22%), and 102.99% (100.87-105.16%), respectively. The geometric mean ratios (GMRs) for the primary pharmacokinetic parameters (Cmax, AUC0-72, and AUC0-∞) between the two formulations and the corresponding 90% confidence intervals (CIs) were all within the range of 80.00-125.00% for both the fasting and fed states. Both treatments have comparable safety profiles. CONCLUSION: The bioequivalence and tolerability of ornidazole tablet reference and test formulations were evaluated among healthy Chinese participants under both fasting and fed conditions. The results indicated that both formulations were bioequivalent and generally well tolerated; besides, the interaction between food and drug may affect drug pharmacokinetics. TRIAL REGISTRATION: CTR20212873, registered on 15 November 2021; ChiCTR2300069098, registered on 7 March 2023.

An aldehyde dehydrogenase gene, GhALDH7B4_A06, positively regulates fiber strength in upland cotton (Gossypium hirsutum L.).

High fiber strength (FS) premium cotton has significant market demand. Consequently, enhancing FS is a major objective in breeding quality cotton. However, there is a notable lack of known functionally applicable genes that can be targeted for breeding. To address this issue, our study used specific length-amplified fragment sequencing combined with bulk segregant analysis to study FS trait in an F2 population. Subsequently, we integrated these results with previous quantitative trait locus mapping results regarding fiber quality, which used simple sequence repeat markers in F2, F2:3, and recombinant inbred line populations. We identified a stable quantitative trait locus qFSA06 associated with FS located on chromosome A06 (90.74-90.83 Mb). Within this interval, we cloned a gene, GhALDH7B4_A06, which harbored a critical mutation site in coding sequences that is distinct in the two parents of the tested cotton line. In the paternal parent Ji228, the gene is normal and referred to as GhALDH7B4_A06O; however, there is a nonsense mutation in the maternal parent Ji567 that results in premature termination of protein translation, and this gene is designated as truncated GhALDH7B4_A06S. Validation using recombinant inbred lines and gene expression analysis revealed that this mutation site is correlated with cotton FS. Virus-induced gene silencing of GhALDH7B4 in cotton caused significant decreases in FS and fiber micronaire. Conversely, GhALDH7B4_A06O overexpression in Arabidopsis boosted cell wall component contents in the stem. The findings of our study provide a candidate gene for improving cotton fiber quality through molecular breeding.

Pharmacokinetics, Bioequivalence, and Safety Evaluation of Two Oral Formulations of Calcium Dobesilate Capsules in Healthy Chinese Volunteers Under Fasting and Fed Conditions.

To determine the pharmacokinetics (PK), safety, and bioequivalence profiles of 0.5-g calcium dobesilate capsules in both fasting and fed states for the test drug and reference drug. A randomized-sequence, single-dose, open-label, 2-period crossover study was conducted in fasted and fed healthy Chinese volunteers (Chinese Clinical Trials Registry identifier: CTR202000268-01). The fasting and fed studies, both involving 24 subjects, were conducted. A single dosage of either the reference or the test preparation was given to each eligible subject in a 1:1 ratio, followed by a 7-day rest interval before the administration of the alternative formulation. After taking the capsules, plasma samples were taken for 48 hours, and using liquid chromatography-tandem mass spectrometry, the calcium dobesilate level was determined. The PK parameters evaluated in the study included the maximum serum concentration (Cmax), area under the plasma concentration-time curve (AUC) from time 0 to the last quantifiable concentration, AUC from time 0 to infinity, half-life, time to Cmax, and terminal elimination rate constant. In addition, the safety evaluation encompassed monitoring fluctuations in vitals (temperature, pulse, and blood pressure) and laboratory tests (urinalysis, hepatic function, blood biochemistry, and hematology), as well as recording the emergence of adverse events (AEs). The geometric mean ratio (GMR) of the test/reference medications was used to assess bioequivalence by determining if the 90% confidence intervals of the GMR fell within the predefined range of 80%-125%. AEs were assessed as safety end points. The study included 48 healthy Chinese volunteers (with n = 24 each for the fasting and the fed conditions), and no subjects dropped out for any reason. The differences in the PK metrics for the test and reference drugs for both conditions were insignificant (P > .05). For bioequivalence, irrespective of whether the food was consumed or not, the range of the 90% confidence intervals of the GMR for Cmax, AUC from time 0 to the last quantifiable concentration, and AUC from time 0 to infinity was between 80% and 125%. In the experiment, no serious AEs were recorded. Our findings revealed that the calcium dobesilate capsules used as the reference and the test drugs were both bioequivalent. Irrespective of whether the healthy Chinese volunteers consumed food or not, the PK and safety profiles were comparable.

[Spectra characteristic effect of different density-resistant maize variety on planting density].

With Chlorophyll Meter SPAD-502 and Canopy Analyzer AccuPAR LP-80, the spectra characteristic effect of different density-resistant maize variety on planting density was studied, and the effect of planting density on photosynthetic performance of maize was discussed. The materials of the experiment were Yinong-103, Xianyu-335, Zhengdan-958 and Denghai-661, the row spacing was 80 cm X 40 cm, the plant spacing was gradually changed from Im to smaller spacing, the densities were 3.33, 3.70, 4.17, 4.50, 4.76, 5.56, 6.67, 6.80, 8.33, 9.00, 11.11, 11.20 and 16.67 planting.m-2 respectively. We studied spectra characteristic effect on planting density, and investigated maize photosynthetic characteristics and density-yield relationship to get high yield. This research can be good case of using maize spectra characteristic to reflect plant photosynthetic characteristics and canopy architecture. The end of this paper was to explore density effect on yield with spectroscopy means.

Lung and bone metastases patterns in osteosarcoma: Chemotherapy improves overall survival.

Osteosarcoma (OS) is a malignant tumor originating from the mesenchymal tissue. Simultaneous reports of lung and bone metastases (BM) in OS are rare in the literature. A total of 353 new cases of lung metastases (LM), 93 new cases of BM, and 59 new cases of LM and BM were diagnosed in the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2019. Univariate and multivariate logistic regression analyses were used to identify risk factors for LM and/or BM, and Cox regression analyses were performed to identify the prognostic factors for LM and/or BM. Kaplan-Meier (K-M) curves and log-rank tests were used to analyze the overall survival of patients with LM and/or BM. LM was diagnosed in 353 patients. Female sex, tumor size >100 mm, telangiectatic OS type, central OS type, N1 stage, other locations, BM, surgical treatments, radiotherapy and chemotherapy were significantly correlated with LM. 93 patients were diagnosed with BM. 25 to 59 years old, T1 stage, presence of LM, liver metastases, radiotherapy, and surgical treatments were significantly correlated with the BM. 59 patients were diagnosed with LM and BM. The chondroblastic OS type, small cell OS type, T1 stage, N1 stage, other locations, liver metastases, radiotherapy, and surgical treatments were significantly correlated with LM and BM. Metastases, radiotherapy, and surgery at the primary site were significantly associated with LM and/or BM. Chemotherapy at the primary site has been shown to be effective in improving the survival rate of LM and/or BM. Of the OS patients with LM, 61.47% died, and older age, BM, no surgery, and no chemotherapy were harmful to survival. 72.04% of OS patients with BM died, and N1 stage, no surgery, and no chemotherapy were harmful for survival. 69.49% of OS patients with LM and BM died, and older age and no chemotherapy were harmful for survival.

Lung and bone metastases patterns in limb osteosarcoma: Surgical treatment of primary site improves overall survival.

Osteosarcoma (OS) is one of the most prevalent malignant bone tumors. The proportion of patients with limb OS was relatively high. Lung metastasis (LM) and bone metastasis are the first and second most common metastatic types of OS, respectively. A total of 270 new cases of LM, 55 new cases of bone metastases (BM), and 36 new cases of lung and BM were diagnosed in the surveillance, epidemiology and end results database from 2010 to 2019. Univariate and multivariate logistic regression analyses were used to identify the risk factors for lung and/or BM, and Cox regression analyses were performed to identify the prognostic factors for lung and/or BM. Kaplan-Meier curves and log-rank tests were used to analyze the overall survival of limb OS patients with lung and/or BM. Female sex, telangiectatic OS type, central OS type, T3 stage, N1 stage, BM, surgical treatments, radiotherapy and chemotherapy were significantly correlated with LM. T3 stage, LM, liver metastases, and radiotherapy significantly correlated with BM. The small cell OS type, T2 stage, T3 stage, N1 stage, liver metastases, and radiotherapy were significantly correlated with lung and BM. Among limb OS patients with LM, the mean survival months of older age, black race, N1 stage, BM, brain metastases, no surgery, and no chemotherapy were lower than those of the control group. In limb OS patients with LM and BM, the mean survival months in the no surgery group was lower than in the surgery group. T stage and radiotherapy significantly influence the occurrence of limb OS with lung and/or BM. Surgery at the primary site has been shown to be effective in improving the survival rate of patients with lung and/or BM.

Cytokines as Prognostic Biomarkers in Osteosarcoma Patients: A Systematic Review and Meta-analysis.

Osteosarcoma is the most prevalent type of primary bone malignancy in children and adolescents. The effect of cytokines on osteosarcoma prognosis has been studied and reported. This meta-analysis aimed to assess the prognostic value of cytokines as osteosarcoma biomarkers. Databases including PubMed, Embase, and Cochrane Library were searched for studies on the prognostic value of cytokines in osteosarcoma. From the eligible studies, data on overall survival (OS), disease-free survival, and metastasis-free survival (MFS) were extracted. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. A total of 11 studies involving 755 patients were included in this analysis. High macrophage migration inhibitory factor (MIF) expression in tumors was significantly associated with shortened OS (HR = 2.01, 95% CI: 1.18-3.42, P = 0.010) and MFS (HR = 2.51, 95% CI: 1.47-4.01, P = 0.001). Elevated T cell immunoglobulin and mucin domain-3 (Tim-3) levels in serum correlated with increased risk of disease progression in patients with osteosarcoma (HR = 3.14, 95% CI: 2.88-3.03, P < 0.001). However, interleukin 6 (IL-6) and tumor necrosis factor were not substantially associated with osteosarcoma prognosis. Owing to a paucity of research, other relevant cytokines [interferon-α/ß receptor, tissue factor, macrophage inhibitory cytokine 1 (MIC-1), and IL-23] could not be combined. In conclusion, MIF levels in tumors and Tim-3 levels in serum can be potential biomarkers of poor prognosis in osteosarcoma. To confirm this finding and implement these biomarkers into clinical applications, additional large-scale, high-quality studies are needed.

Lung metastases pattern in limb osteosarcoma: A population-based study from 2010 to 2018.

Osteosarcoma (OS) is one of the most prevalent malignant bone tumors. The proportion of limb OS is relatively high, and lung metastases (LM) are one of the most prevalent metastatic types. A total of 1694 new cases of limb OS were identified in the surveillance, epidemiology and end results (SEER) database from 2010 to 2018. Cox regression analyze was performed to identify prognostic factors for limb OS with LM, and univariate and multivariate logistic regression analyses were used to assess risk factors for LM. Kaplan-Meier analysis was performed to calculate overall survival for LM, and a log-rank test was used for comparison. A total of 287 patients (16.94%) were diagnosed with limb OS with LM. 25 to 59 years old (odds ratio, OR 0.68; 95% confidence interval, CI: 0.46-0.99), larger than 100 mm tumors (OR 3.65, 95% CI: 1.54-8.64), telangiectatic osteosarcoma type (OR 0.24, 95% CI: 0.07-0.81), central osteosarcoma type (OR 0.44, 95% CI: 0.19-0.99), T2 stage (OR 2.59, 95% CI: 1.18-5.69), N1 stage (OR 7.79, 95% CI: 3.90-15.56), presence of bone metastases (OR 4.58, 95% CI: 2.43-8.63) and surgical treatments of primary site (OR 0.22, 95% CI: 0.14-0.33) were significant correlations with lung metastases. Elderly age, black race and absence of surgery were harmful for survival. Age between 25 and 59 years, telangiectatic osteosarcoma and central osteosarcoma were identified as high-risk factors in limb OS patients with LM, and surgical treatment of the primary site significantly increased the survival rate of LM in these patients.

A retrospective study: screening failure analysis of 1,058 healthy volunteers in phase I clinical trials.

BACKGROUND: Phase I clinical trials play an important role in the follow-up clinical trials and even the drug registration and marketing. However, the screening success ratio in phase I clinical trials is low, and the screening process of the trials consumes a significant amount of human and material resources, but the results are unsatisfactory. At present, there is no large sample data analysis for screening failure in phase I clinical trials. It is therefore urgent to find the reasons for screening failure in phase I clinical trials. METHODS: A total of 1,058 healthy volunteers who failed the screening in 11 phase I clinical trials were retrospectively collected from October 2018 to June 2021 in Cangzhou Central Hospital. Data on all participants who failed screening for the study were analyzed (descriptive analysis) and reasons for their non-randomization were classified, as well as the differences of main screening failures between four years. RESULTS: A total of 1,466 healthy volunteers were enrolled in the 11 trials, and among them 1,058 subjects failed the screening. The total screening success ratio of our study was only 27.8%, the highest being 38.5% and the lowest being 18.2%. The top 3 reasons for non-randomization were abnormalities in blood biochemistry tests (23.3%), vital sign examination (19.3%), and electrocardiogram (ECG) (16.6%). Abnormal blood biochemistry was the main reason between 2019 and 2021, except for 2018 in which it was the second reason. CONCLUSIONS: Screening failure is a burdensome issue which various clinical trial sites must contend with. Investigators can still take some effective measures by strengthening the in-depth understanding of informed consent, paying attention to the quality of test samples, a correcting definition of no clinical significance (NCS). Also, low-cost and non-invasive examinations can be arranged first to better protect the volunteers and reduce the screening costs of clinical trials. To our delight, we find people's attention to the annual physical examination may help to screen healthy volunteers. Overall, this study shows that it is crucial and professional to develop a screening plan to minimize the resultant impact on timelines and budgets of phase I clinical trials enrolling healthy volunteers.

Genome-wide characterization of carotenoid oxygenase gene family in three cotton species and functional identification of GaNCED3 in drought and salt stress.

Cotton that serves natural fiber for the textile industry is an important industrial crop. However, abiotic stress imposed a significant negative impact on yield and quality of cotton fiber. Carotenoid cleavage oxygenases (CCOs) that specifically catalyze the cleavage of carotenoid are essential for plant growth and development and abiotic stress response. While information of cotton CCOs and their potential functions in abiotic stress is still far from satisfactory, which imposes restrictions on application in genetic breeding for stress resistance. In this study, 15, 15, and 30 CCOs were identified from Gossypium arboreum, Gossypium raimondii, and Gossypium hirsutum, respectively. Phylogenetic relationship indicated that CCO genes could be classified into two groups (NCEDs and CCDs). Cis-elements prediction showed that there were 18 types of stress-related cis-elements in promoter regions. Analysis with transcriptome data revealed tissue-specific expression pattern of cotton CCOs. qRT-PCR analysis revealed only that GhNCED3a_A/D and GhNCED3c_A/D had strong response to drought, salt, and cold stress, while GhCCD1_A/D and GhCCD4_A showed relatively slight expression changes. Virus-induced gene silencing of GaNCED3a, the ortholog gene of GhNCED3a_A/D, suggested that silenced plants exhibited decreased resistance not only to drought but also to salt, with significantly reduced proline content, and high malondialdehyde content and water loss rate. In addition, stress response genes RD29A, DREB1A, and SOS1 significantly downregulated under drought and salt stress in silenced plants compared to control plants, indicating that GaNCED3a played an important role in drought and salt response. The results provided valuable insights into function analysis of cotton CCOs in abiotic stress response, and suggested potential benefit genes for stress-resistant breeding.

Apical ligand substitution, shape recognition, vapor-adsorption phenomenon, and microcalorimetry for a pillared bilayer porous framework that shrinks or expands in crystal-to-crystal manners upon change in the cobalt(II) coordination environment.

A 2D pillared bilayer coordination polymer, [Co(5-NH(2)-bdc)(bpy)(0.5)(H(2)O)] x 2 H(2)O (1; 5-NH(2)-bdc = 5-aminoisophthalate; bpy = 4,4'-bipyridine) has been hydrothermally synthesized and shows a novel microporous host framework with 1D channels and high thermal stability (approximately 400 degrees C). The framework of 1 exhibits reversible single-crystal-to-single-crystal transformations upon removing and rebinding the coordinated waters as well as replacing them with MeOH and EtOH from the solvent. X-ray crystallography reveals that the coordination geometry of Co(II) changes from octahedron to square pyramid, as well as the shrinkage/expansion of pore deformation in respect to the subsequent shear motion of bpy pillars and vice versa. The dehydrated form 2 exhibits a shape recognition ability, which can accommodate linear molecules, such as MeCN and 2-propynyl alcohol, and interesting storage capabilities for oversized MeOH, EtOH, and benzene molecules, concomitant with spongelike dynamic transformation. The microcalorimetric study indicates that the crystalline state-liquid guest exchange and guest inclusion processes (1 superset MeOH or EtOH, 2 superset MeOH, EtOH or MeCN) are feasibly endothermic reactions with the values of molar enthalpy, DeltaH(theta)(m), of +21.38(96), +12.68(85), +25.92(86), +17.03(57), and +14.93(75) kJ mol(-1), respectively.