Allele-aware chromosome-scale assembly of the allopolyploid genome of hexaploid Ma bamboo (Dendrocalamus latiflorus Munro).

Dendrocalamus latiflorus Munro is a woody clumping bamboo with rapid shoot growth. Both genetic transformation and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing techniques are available for D. latiflorus, enabling reverse genetic approaches. Thus, D. latiflorus has the potential to be a model bamboo species. However, the genome sequence of D. latiflorus has remained unreported due to its polyploidy and large genome size. Here, we sequenced the D. latiflorus genome and assembled it into three allele-aware subgenomes (AABBCC), representing the largest genome of a major bamboo species. We assembled 70 allelic chromosomes (2, 737 Mb) for hexaploid D. latiflorus using both single-molecule sequencing from the Pacific Biosciences (PacBio) Sequel platform and chromosome conformation capture sequencing (Hi-C). Repetitive sequences comprised 52.65% of the D. latiflorus genome. We annotated 135 231 protein-coding genes in the genome based on transcriptomes from eight different tissues. Transcriptome sequencing using RNA-Seq and PacBio single-molecule real-time long-read isoform sequencing revealed highly differential alternative splicing (AS) between non-abortive and abortive shoots, suggesting that AS regulates the abortion rate of bamboo shoots. This high-quality hexaploid genome and comprehensive strand-specific transcriptome datasets for this Poaceae family member will pave the way for bamboo research using D. latiflorus as a model species.

Cirmtuzumab blocks Wnt5a/ROR1 stimulation of NF-κB to repress autocrine STAT3 activation in chronic lymphocytic leukemia.

Coculture of nurse-like cells (NLCs) with chronic lymphocytic leukemia (CLL) cells induced leukemia cell phosphorylation of STAT3 (pSTAT3), which could be blocked by anti-Wnt5a antibodies or the anti-ROR1 monoclonal antibody, cirmtuzumab. Time-course studies revealed Wnt5a could induce activation of NF-κB within 30 minutes, but required more than 3 hours to induce pSTAT3. Culture of isolated CLL cells for 24 hours revealed Wnt5a-induced expression of interleukin 6 (IL-6), IL-8, CCL2, CCL3, CCL4, and CXCL1, which in turn could induce pSTAT3 in unstimulated CLL cells within 30 minutes. We found that Wnt5a could induce CLL cell expression of NF-κB target genes, including IL-6, and that this effect could be blocked by cirmtuzumab or drugs that inhibit NF-κB. Examination of CLL cells and plasma collected from patients treated with cirmtuzumab revealed reduced levels of phosphorylated p65 and diminished expression of NF-κB and STAT3 target genes in CLL cells, as well as lower plasma levels of IL-6, in the samples after therapy. Collectively, these studies indicate that Wnt5a/ROR1-dependent signaling contributes to CLL cell activation of NF-κB, which in turn causes autocrine IL-6-induced activation of pSTAT3. As such, this study demonstrates that cirmtuzumab can inhibit leukemia cell activation of both NF-κB and STAT3 in patients with CLL.

Wnt5a induces ROR1 to recruit DOCK2 to activate Rac1/2 in chronic lymphocytic leukemia.

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncoembryonic protein expressed on chronic lymphocytic leukemia (CLL) that can serve as a receptor for Wnt5a, which can promote leukemia cell migration, proliferation, and survival. We found Wnt5a could induce ROR1 to complex with DOCK2 (dedicator of cytokinesis 2) and induce activation of Rac1/2; these effects could be blocked by cirmtuzumab, a humanized anti-ROR1 monoclonal antibody. We find that silencing DOCK2 specifically impaired the capacity of Wnt5a to induce activation of Rac1/2 or enhance CLL cell proliferation. We generated truncated forms of ROR1 and found the cytoplasmic proline-rich domain (PRD) of ROR1 was required for Wnt5a to induce ROR1 to complex with DOCK2 and activate Rac1/2 in the CLL cell-line MEC1. We introduced single amino acid substitutions of proline (P) to alanine (A) in the ROR1-PRD at potential binding sites for the Src-homology 3 domain of DOCK2. In contrast to wild-type ROR1, or other ROR1 P→A variants, ROR1P808A was unable to recruit DOCK2 in response to Wnt5a. Moreover, unlike MEC1 cells transfected with wild-type ROR1 or ROR1 with P→A substitutions at positions 784, 826, or 841, MEC1 cells transfected to express ROR1P808A did not have a growth advantage over MEC1 cells that do not express ROR1. This study reveals that the recruitment of DOCK2 may be critical for the capacity of Wnt5a to enhance CLL proliferation, which may contribute to the observed increased tendency for disease progression in patients who have CLL cells that express high levels of ROR1.

High-level ROR1 associates with accelerated disease progression in chronic lymphocytic leukemia.

ROR1 is an oncoembryonic orphan receptor found on chronic lymphocytic leukemia (CLL) B cells, but not on normal postpartum tissues. ROR1 is a receptor for Wnt5a that may complex with TCL1, a coactivator of AKT that is able to promote development of CLL. We found the CLL cells of a few patients expressed negligible ROR1 (ROR1Neg), but expressed TCL1A at levels comparable to those of samples that expressed ROR1 (ROR1Pos). Transcriptome analyses revealed that ROR1Neg cases generally could be distinguished from those that were ROR1Pos in unsupervised gene-expression clustering analysis. Gene-set enrichment analyses demonstrated that ROR1Neg CLL had lower expression and activation of AKT signaling pathways relative to ROR1Pos CLL, similar to what was noted for leukemia that respectively developed in TCL1 vs ROR1xTCL1 transgenic mice. In contrast to its effect on ROR1Pos CLL, Wnt5a did not enhance the proliferation, chemotaxis, or survival of ROR1Neg CLL. We examined the CLL cells from 1568 patients, which we randomly assigned to a training or validation set of 797 or 771 cases, respectively. Using recursive partitioning, we defined a threshold for ROR1 surface expression that could segregate samples of the training set into ROR1-Hi vs ROR1-Lo subgroups that differed significantly in their median treatment-free survival (TFS). Using this threshold, we found that ROR1-Hi cases had a significantly shorter median TFS and overall survival than ROR1-Lo cases in the validation set. These data demonstrate that expression of ROR1 may promote leukemia-cell activation and survival and enhance disease progression in patients with CLL.

ROR1 can interact with TCL1 and enhance leukemogenesis in Eµ-TCL1 transgenic mice.

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncoembryonic antigen found on chronic lymphocytic leukemia (CLL) B cells, but not on normal adult tissues. We generated transgenic (Tg) mice with human ROR1 regulated by the murine Ig promoter/enhancer. In contrast to nontransgenic littermates, such animals had B-cell-restricted expression of ROR1 and could develop clonal expansions of ROR1(bright)CD5(+)B220(low) B cells resembling human CLL at ≥ 15 mo of age. Because immune-precipitation and mass spectrometry studies revealed that ROR1 could complex with T-cell leukemia 1 (TCL1) in CLL, we crossed these animals with Eµ-TCL1-Tg (TCL1) mice. Progeny with both transgenes (ROR1 × TCL1) developed CD5(+)B220(low) B-cell lymphocytosis and leukemia at a significantly younger median age than did littermates with either transgene alone. ROR1 × TCL1 leukemia B cells had higher levels of phospho-AKT than TCL1 leukemia cells and expressed high levels of human ROR1, which we also found complexed with TCL1. Transcriptome analyses revealed that ROR1 × TCL1 leukemia cells had higher expression of subnetworks implicated in embryonic and tumor-cell proliferation, but lower expression of subnetworks involved in cell-cell adhesion or cell death than did TCL1 leukemia cells. ROR1 × TCL1 leukemia cells also had higher proportions of Ki-67-positive cells, lower proportions of cells undergoing spontaneous apoptosis, and produced more aggressive disease upon adoptive transfer than TCL1 leukemia cells. However, treatment with an anti-ROR1 mAb resulted in ROR1 down-modulation, reduced phospho-AKT, and impaired engraftment of ROR1 × TCL1 leukemia cells. Our data demonstrate that ROR1 accelerates development/progression of leukemia and may be targeted for therapy of patients with CLL.

Ovarian cancer stem cells express ROR1, which can be targeted for anti-cancer-stem-cell therapy.

Although initially responsive to chemotherapy, many patients with ovarian cancer subsequently develop relapsed and potentially fatal metastatic disease, which is thought to develop from cancer stem cells (CSCs) that are relatively resistant to conventional therapy. Here, we show that CSCs express a type I receptor tyrosine kinase-like orphan receptor (ROR1), which is expressed during embryogenesis and by many different cancers, but not normal postpartum tissues. Ovarian cancers with high levels of ROR1 had stem cell-like gene-expression signatures. Furthermore, patients with ovarian cancers with high levels of ROR1 had higher rates of relapse and a shorter median survival than patients with ovarian cancers that expressed low-to-negligible amounts of ROR1. We found that ROR1-positive (ROR1(+)) cells isolated from primary tumor-derived xenografts (PDXs) also expressed aldehyde dehydrogenase 1 (ALDH1) and had a greater capacity to form spheroids and to engraft immune-deficient mice than did ROR1-negative (ROR1(Neg)) ovarian cancer cells isolated from the same tumor population. Treatment with UC-961, an anti-ROR1 mAb, or shRNA silencing of ROR1 inhibited expression of the polycomb ring-finger oncogene, Bmi-1, and other genes associated with the epithelial-mesenchymal transition. Moreover, shRNA silencing of ROR1, depletion of ROR1(+) cells, or treatment with UC-961 impaired the capacity of ovarian cancer cells to form spheroids or tumor xenografts. More importantly, treatment with anti-ROR1 affected the capacity of the xenograft to reseed a virgin mouse, indicating that targeting ROR1 may affect CSC self-renewal. Collectively, these studies indicate that ovarian CSCs express ROR1, which contributes to their capacity to form tumors, making ROR1 a potential target for the therapy of patients with ovarian cancer.

miR-150 influences B-cell receptor signaling in chronic lymphocytic leukemia by regulating expression of GAB1 and FOXP1.

We examined the microRNAs (miRNAs) expressed in chronic lymphocytic leukemia (CLL) and identified miR-150 as the most abundant, but with leukemia cell expression levels that varied among patients. CLL cells that expressed ζ-chain-associated protein of 70 kDa (ZAP-70) or that used unmutated immunoglobulin heavy chain variable (IGHV) genes, each had a median expression level of miR-150 that was significantly lower than that of ZAP-70-negative CLL cells or those that used mutated IGHV genes. In samples stratified for expression of miR-150, CLL cells with low-level miR-150 expressed relatively higher levels of forkhead box P1 (FOXP1) and GRB2-associated binding protein 1 (GAB1), genes with 3' untranslated regions having evolutionary-conserved binding sites for miR-150. High-level expression of miR-150 could repress expression of these genes, which encode proteins that enhance B-cell receptor signaling, a putative CLL-growth/survival signal. Also, high-level expression of miR-150 was a significant independent predictor of longer treatment-free survival or overall survival, whereas an inverse association was observed for high-level expression of GAB1 or FOXP1 for overall survival. This study demonstrates that expression of miR-150 can influence the relative expression of GAB1 and FOXP1 and the signaling potential of the B-cell receptor, thereby possibly accounting for the noted association of expression of miR-150 and disease outcome.

MicroRNA-155 influences B-cell receptor signaling and associates with aggressive disease in chronic lymphocytic leukemia.

High-level leukemia cell expression of micro-RNA 155 (miR-155) is associated with more aggressive disease in patients with chronic lymphocytic leukemia (CLL), including those cases with a low-level expression of ζ-chain-associated protein of 70 kD. CLL with high-level miR-155 expressed lower levels of Src homology-2 domain-containing inositol 5-phosphatase 1 and were more responsive to B-cell receptor (BCR) ligation than CLL with low-level miR-155. Transfection with miR-155 enhanced responsiveness to BCR ligation, whereas transfection with a miR-155 inhibitor had the opposite effect. CLL in lymphoid tissue expressed higher levels of miR155HG than CLL in the blood of the same patient. Also, isolated CD5(bright)CXCR4(dim) cells, representing CLL that had been newly released from the microenvironment, expressed higher levels of miR-155 and were more responsive to BCR ligation than isolated CD5(dim)CXCR4(bright) cells of the same patient. Treatment of CLL or normal B cells with CD40-ligand or B-cell-activating factor upregulated miR-155 and enhanced sensitivity to BCR ligation, effects that could be blocked by inhibitors to miR-155. This study demonstrates that the sensitivity to BCR ligation can be enhanced by high-level expression of miR-155, which in turn can be induced by crosstalk within the tissue microenvironment, potentially contributing to its association with adverse clinical outcome in patients with CLL.

Targeting chronic lymphocytic leukemia cells with a humanized monoclonal antibody specific for CD44.

Chronic lymphocytic leukemia (CLL) cells express high levels of CD44, a cell-surface glycoprotein receptor for hyaluronic acid. We found that a humanized mAb specific for CD44 (RG7356) was directly cytotoxic for leukemia B cells, but had little effect on normal B cells. Moreover, RG7356 could induce CLL cells that expressed the zeta-associated protein of 70 kDa (ZAP-70) to undergo caspase-dependent apoptosis, independent of complement or cytotoxic effector cells. The cytotoxic effect of this mAb was not mitigated when the CLL cells were cocultured with mesenchymal stromal cells (MSCs) or hyaluronic acid or when they were stimulated via ligation of the B-cell receptor with anti-µ. RG7356 induced rapid internalization of CD44 on CLL cells at 37 °C, resulting in reduced expression of ZAP-70, which we found was complexed with CD44. Administration of this mAb at a concentration of 1 mg/kg to immune-deficient mice engrafted with human CLL cells resulted in complete clearance of engrafted leukemia cells. These studies indicate that this mAb might have therapeutic activity, particularly in patients with CLL that express ZAP-70.

Increased calcineurin expression after pilocarpine-induced status epilepticus is associated with brain focal edema and astrogliosis.

Calcineurin plays an important role in the development of neuronal excitability, modulation of receptor's function and induction of apoptosis in neurons. It has been established in kindling models that status epilepticus induces brain focal edema and astrocyte activation. However, the role of calcineurin in brain focal edema and astrocyte activation in status epilepticus has not been fully understood. In this study, we employed a model of lithium-pilocarpine-induced status epilepticus and detected calcineurin expression in hippocampus by immunoblotting, brain focal edema by non-invasive magnetic resonance imaging (MRI-7T) and astrocyte expression by immunohistochemistry. We found that the brain focal edema was seen at 24 h after status epilepticus, and astrocyte expression was obviously seen at 7 d after status epilepticus. Meanwhile, calcineurin expression was seen at24 h and retained to 7 d after status epilepticus. A FK506, a calcineurin inhibitor, remarkably suppressed the status epilepticus-induced brain focal edema and astrocyte expression. Our data suggested that calcineurin overexpression plays a very important role in brain focal edema and astrocyte expression. Therefore, calcineurin may be a novel candidate for brain focal edema occurring and intracellular trigger of astrogliosis in status epilepticus.

Fatty acid composition of developing tree peony (Paeonia section Moutan DC.) seeds and transcriptome analysis during seed development.

BACKGROUND: Tree peony (Paeonia section Moutan DC.) is known for its excellent ornamental and medicinal values. In 2011, seeds from P. ostii have been identified as novel resource of α-linolenic acid (ALA) for seed oil production and development in China. However, the molecular mechanism on biosynthesis of unsaturated fatty acids in tree peony seeds remains unknown. Therefore, transcriptome data is needed to better understand the underlying mechanisms. RESULTS: In this study, lipid accumulation contents were measured using GC-MS methods across developing tree peony seeds, which exhibited an extraordinary ALA content (49.3%) in P. ostii mature seeds. Transcriptome analysis was performed using Illumina sequencing platform. A total of 144 million 100-bp paired-end reads were generated from six libraries, which identified 175,874 contigs. In the KEGG Orthology enrichment of differentially expressed genes, lipid metabolism pathways were highly represented categories. Using this data we identified 388 unigenes that may be involved in de novo fatty acid and triacylglycerol biosynthesis. In particular, three unigenes (SAD, FAD2 and FAD8) encoding fatty acid desaturase with high expression levels in the fast oil accumulation stage compared with the initial stage of seed development were identified. CONCLUSIONS: This study provides the first comprehensive genomic resources characterizing tree peony seeds gene expression at the transcriptional level. These data lay the foundation for further understanding of molecular mechanism responsible for lipid biosynthesis and the high unsaturated fatty acids (especially ALA) accumulation. Meanwhile, it provides theoretical base for potential oilseed application in the respect of n-6 to n-3 ratio for human diets and future regulation of target healthy components of oils.

Impact of oxygen concentration on growth of mesenchymal stromal cells from the marrow of patients with chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) cells interact in the marrow with mesenchymal stromal cells (MSCs), which can enhance CLL-cells' resistance to spontaneous or drug-induced apoptosis. Here we examined the effect of oxygen on the growth and function of MSCs from marrow aspirates of CLL patients. Cultures in ambient oxygen provided for poor recovery and growth of MSCs, which developed features of cell senescence. However, MSCs were propagated readily from the same cells when they were cultured at a physiologic oxygen concentration of 5%. Such MSCs promoted short-term CLL-cell survival in either 5% or ambient O2. However, longer-term CLL-cell survival was enhanced when the cocultures were maintained in 5% O2 versus 21% O2 because of increased MSC proliferation and production of soluble prosurvival factors, such as CXCL12. This study establishes the importance of physiologic oxygen concentration in the propagation and function of MSCs derived from marrow aspirates of CLL patients in vitro.

Calculation of additional load and deformation of the receiving well enclosure structure caused by shield tunneling.

The bulkhead additional thrust during shield tunneling, the force of friction between shield and soil, and the additional grouting pressure can cause additional stress in the surrounding soil, thereby disturbing existing buildings and structures. However, few studies focused on the disturbance situation when the shield tunneling machine approaches the receiving well. If the additional stress and deformation of the receiving well are too excessive, it could result in the collapse of the receiving well. Based on the two-stage method, this study derived the calculation formula of the additional stress and deformation of the receiving well enclosure structure caused by shield tunneling. Taking a shield machine receiving engineering as the context, this study established a numerical simulation model and compared theoretical calculation, the results of numerical simulation model and on-site monitoring data. Finally, the additional stress of the receiving well is analyzed. The research findings demonstrate that the theoretical prediction results, numerical simulation calculation results, and on-site monitoring data exhibit relatively small calculation errors, which validated the applicability of the theoretical prediction formula and numerical simulation model. As the distance between the shield machine and the receiving well decreases, the disturbance to the receiving well increases sharply. When the distance between the cutter head and the receiving well is less than three times the shield length, it is crucial to enhance the deformation monitoring of the receiving well. The primary factors affecting the additional load and deformation of the receiving well enclosure structure are the force of friction between shield and soil and the additional thrust of the cutterhead. The disturbance caused by the additional grouting pressure on the enclosure structure can be ignored.

Sex Differences in Outcomes of Hepatobiliary and Pancreatic Surgery with Accelerated Rehabilitation.

BACKGROUND: Sex, in the sense of gender, is a major social demographic characteristic that has been shown to affect health care outcomes. The concept of enhanced recovery after surgery (ERAS) is an effective perioperative management measure that can reduce the perioperative stress response in patients. However, there are few studies on the differences between male and female patients under this type of care. We aimed to analyze sex differences in clinical characteristics among patients undergoing hepatobiliary and pancreatic surgery with accelerated rehabilitation. METHODS: We enrolled patients who underwent liver, biliary tract, and gallbladder operations in the Department of Hepatobiliary and Pancreatic Surgery of Taizhou Hospital, Zhejiang Province, China, from April 2021 to July 2021. Key measures were collected for patients undergoing perioperative accelerated rehabilitation (i.e., the case group). The study group was assembled by performing 1:1 matching for age, sex, chronic disease, and type of surgery. Postoperative risk assessment, postoperative recovery indicators, and postoperative length of hospital stay (days) were compared between male and female patients. RESULTS: A total of 226 surgical patients were enrolled, including 109 male (48.23%) and 117 female patients (51.77%). The outcomes, presented as the median (min, max), were as follows: pulmonary rehabilitation risk assessment in females (1(0,3)) and males (0(0,2)), postoperative nausea and vomiting in females (2(1,3)) and males (1(0,2)), and time to first defecation in females (31(4,61)) and males (36(10,78)). Significant differences were indicated by p values < 0.05. CONCLUSION: We identified sex differences in the clinical prognosis and performance of perioperative patients undergoing hepatobiliary and pancreatic surgery with accelerated rehabilitation. The perioperative pulmonary rehabilitation risk of male patients was higher than that of female patients, and the time to first defecation was longer in male than in female patients. The incidence of nausea and vomiting in women was higher than in men.

Variation in Nitrogen Utilization and Nutrient Composition across Various Organs under Different Strip Logging Management Models in Moso Bamboo (Phyllostachys edulis) Forest.

The rapid restoration and renewal of the moso bamboo logging zone after strip logging has emerged as a key research area, particularly regarding whether nutrient accumulation and utilization in reserve zones can aid in the restoration and regeneration of the logging zone. In this study, a dynamic 15N isotope tracking experiment was conducted by injecting labeled urea fertilizer into bamboo culms. Logging zones and reserve zones of 6 m, 8 m, and 10 m widths were established. The conventional selective logging treatment served as a control (Con). Measurements were taken in May and October to assess the differences in nitrogen accumulation ability, utilization rates, and nutrient content across different organs in bamboo forests at different growth stages and under different treatments. Principal component analysis was conducted to evaluate and determine the importance of each indicator and strip logging treatment comprehensively. The results showed that various bamboo organs exhibited higher nitrogen accumulation and utilization rates during the peak growth period compared to the late growth period. Leaves had the highest nitrogen accumulation and utilization rates than the other organs. The average C content in various bamboo organs under different logging treatments exhibited subtle differences, irrespective of variation in logging width treatments. Bamboo culm exhibited the highest carbon accumulation. The C content in various bamboo organs was higher during the peak growth period than in the late growth period. The nitrogen content peaked in the leaves during the two growth stages and was significantly higher compared to the other organs. Most bamboo organs in the logging zones exhibited relatively higher nitrogen content than in the reserve zone and Con group. The P content was highest in bamboo leaves compared with other organs across the different strip logging treatments. Principal component analysis revealed relatively high absolute values of the coefficients for the C content, bamboo stump C content, and culm Ndff%. Log8 and Res10 zones had the highest comprehensive evaluation scores, indicating that Log8 and Res10 had the best effect on the promotion of nitrogen utilization and nutrient accumulation in various organs of moso bamboo.

De novo Whole-Genome Assembly of the 10-Gigabase Fokienia Hodginsii Genome to Reveal Differential Epigenetic Events Between Callus and Xylem.

Fokienia hodginsii (F. hodginsii), belonging to the genus Fokienia of the Cupressaceae. F. hodginsii has significant application value due to its wood properties and great research value in evolutionary studies as a gymnosperm. However, the genome of F. hodginsii remains unknown due to the large size of gymnosperms genome. Pacific Bioscience sequencing, Hi-C mapping, whole-genome Bisulfite Sequencing (BS-Seq), long-read isoform sequencing (Iso-Seq), direct RNA sequencing (DRS), quantitative proteomics, and metabonomics analysis are employed to facilitate genome assembly, gene annotation, and investigation into epigenetic mechanisms. In this study, the 10G F. hodginsii genome is assembled into 11 chromosomes. Furthermore, 50 521 protein-coding genes are annotated and determined that 65% of F. hodginsii genome comprises repetitive sequences. It is discovered that transposable element (TE)-including introns is associated with higher expression. The DNA methylome of F. hodginsii reveals that xylem has a higher DNA methylation level compared to callus. Moreover, DRS reveals the significant alterations in RNA full-length ratio, which potentially associated with poly(A) length (PAL) and alternative polyadenylation (APA). Finally, the morphology measurement and metabonomics analysis revealed the difference of 14 cultivars. In summary, the genomes and epigenetics datasets provide a molecular basis for callus formation in the gymnosperm family.

The onco-embryonic antigen ROR1 is expressed by a variety of human cancers.

ROR1 is an orphan-receptor tyrosine-kinase-like surface antigen that is expressed by many tissues during embryogenesis, some B-cell malignancies, and various cancer cell lines but not by virtually all normal adult tissues. Here, we report that large proportions of many different human cancers also express ROR1, particularly those cancers that have high-grade histology. Primary cancers that expressed ROR1 more commonly expressed high levels of phosphorylated AKT (p-AKT) and phosphorylated cAMP response element binding-factor (p-CREB) than similar cancers that lacked expression of ROR1. Induced expression of ROR1 could enhance basal p-AKT and p-CREB levels and could promote the growth of a cancer cell line, MEC1. Conversely, silencing ROR1 resulted in lower levels of p-AKT and p-CREB, which was associated with impaired tumor cell growth. In summary, this study found that many different human cancers express ROR1 and that ROR1 may play a functional role in promoting tumor cell growth, suggesting that this orphan-receptor tyrosine-kinase-like protein may be a potential target for therapy directed against a variety of human cancers.

Plate versus intramedullary nail fixation in the treatment of humeral shaft fractures: an updated meta-analysis.

BACKGROUND: Regarding the treatment of humeral shaft fractures, the choice of plating or intramedullary nailing remains controversial. Previous randomized controlled trials and meta-analyses failed to draw a unanimous conclusion. To guide clinical decision making, we conducted an updated meta-analysis on the optimal treatment of humeral shaft fractures. METHODS: We identified eligible studies published from 1969 to July 2011 using the Cochrane Library; Cochrane Bone, Joint and Muscle Trauma Group; MEDLINE; Embase; OVID; and Google Scholar and manually searched the references of relevant studies. Randomized controlled trials that compared nailing and plating in the treatment of humeral shaft fractures were included. After the methodologic assessment, available data were extracted and statistically reviewed. The primary outcomes were nonunion, delayed union, postoperative infection, reoperation, and radial nerve palsy. The secondary outcomes were restriction of shoulder motion, shoulder impingement, iatrogenic fracture comminution, and implant failure. RESULTS: We included 10 studies comparing plating and nailing in patients with humeral shaft fractures, comprising 439 participants. Plating reduced the risk of shoulder impingement and shoulder restriction in comparison with nailing. Regarding reoperation risk, a secondary sensitivity analysis showed the finding favoring plating over nailing remained unstable. Otherwise, no significant differences were found in postoperative infection, nonunion, delayed union, radial nerve palsy, iatrogenic fracture comminution, and implant failure between groups. CONCLUSIONS: On the basis of current evidence, both plating and nailing can achieve a similar treatment effect on humeral shaft fractures, but plating may reduce the occurrence of shoulder problems. Randomized controlled trials with larger sample sizes using appropriate blinding methods are needed to confirm these findings. LEVEL OF EVIDENCE: Level II, Meta-analysis of prospective comparative trials.

Applicability of risk compensation to the relationship between health behaviors and COVID-19 vaccination among inpatients in Taizhou, China.

Aim: Based on the risk compensation theory, this study was designed to investigate the relationship between health behaviors of inpatients and COVID-19 vaccination during the epidemic with regard to the Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Taizhou, China. Subject and methods: We conducted an online self-administered survey with a group of inpatients in a grade III, class A hospital in Taizhou, China, from February 27, 2022, to March 8, 2022. A total of 562 complete questionnaires were collected, and 18 questionnaires completed in under 180 seconds were rejected, leaving a total of 544 (96.8%) valid questionnaires collected. The participants who had received a COVID-19 vaccine were asked to describe the differences in their health behaviors before and after the vaccination, and the data were analyzed using SPSS Statistics version 22.0 software. Results: There were significant differences in the percentage of individuals wearing masks (97.2% and 78.9%, P < 0.001) and the percentage of hand washing after taking off the mask (89.1% and 63.2%, P < 0.001) between the inoculated group and the uninoculated group; however, there were no significant differences in other health behaviors. The participants showed better health behaviors (handwashing and wearing a mask) after the vaccination than prior to it. Conclusions: Our findings suggest that the Peltzman effect did not increase risk behaviors during the Omicron epidemic. There was no reduction in health behaviors among inpatients after the COVID-19 vaccine, which may have even improved their health behaviors.

Effects of Different Heterogeneous Nutrient Environments on the Growth and Activities of Enzymes in the Roots of Fokienia hodginsii Families.

Currently, research on the F. hodginsii asexual lineage primarily focuses on the screening of growth traits and the control of single fertilizer applications. The effects of the heterogeneity of soil nutrients on root growth and activity have not been studied in detail. Therefore, we propose forest management measures to improve the foraging ability of forest trees in conjunction with stand productivity. In this experiment, annual containerized seedlings of 10 free-pollinated F. hodginsii lines from a primary asexual seed orchard were used as test subjects, and three heterogeneous nutrient environments of nitrogen (N), phosphorus (P), and potassium (K) were constructed. In contrast, homogeneous nutrient environments were used as the control to carry out potting experiments, to study the growth of F. hodginsii lines and the differences in the activities of root enzymes under the three heterogeneous nutrient environments, and to carry out the comprehensive evaluation using the principal component and cluster analysis method. The results were as follows: (1) The seedling height of F. hodginsii family lines under a homogeneous nutrient environment was significantly higher than that of all heterogeneous nutrient environments; the diameter of the ground was the highest under N heterogeneous nutrient environment and significantly higher than that of all the other nutrient environments; the biomass of the root system was the highest under P heterogeneous nutrient environment, which was significantly higher than that of homogeneous nutrient environment and K heterogeneous nutrient environment. The catalase (CAT) activity of F. hodginsii roots was higher than that of homogeneous nutrients in all heterogeneous nutrient environments but not significant, and the superoxide dismutase (SOD) activity was slightly higher than that of K heterogeneous and homogeneous nutrient environments in N and P heterogeneous nutrient environments. SOD activity was slightly higher than that of K heterogeneous and homogeneous nutrient environments under N, and P. peroxidase (POD) activity in the F. hodginsii root system was the highest under the P heterogeneous nutrient environment, which was significantly higher than that of the other nutrient environments. Unlike the activities of the enzymes, the content of malondialdehyde (MDA) in the roots of F. hodginsii was higher in the heterogeneous environment than in all the other nutrient environments. (2) Under N and P heterogeneous nutrient environments, lines 552 and 590 had higher seedling height, ground diameter, and root enzyme activity, while root biomass was highest in line 544; and under K heterogeneous nutrient environments, line 591 had higher seedling height, ground diameter, and root enzyme activity while root biomass was highest in line 551. In contrast to the patterns of seedling height, accumulation of root biomass and activities of root enzymes, family No. 590 had the highest ground diameter of all the F. hodginsii families under the heterogeneous nutrient environments. Family No. 547 had the highest MDA content. In conclusion, it can be seen that N heterogeneous and homogeneous nutrient environments can significantly increase the seedling height and diameter of F. hodginsii compared with P and K heterogeneous nutrient environments, and N and P heterogeneous nutrient environments can also increase the root biomass, root enzyme activities and significantly reduce the MDA content of F. hodginsii. According to the principal component analysis and cluster analysis, it can be seen that among the 10 F. hodginsii family lines, family lines 590 and 552 have higher evaluation in growth, root biomass accumulation, and enzyme activity.