The Slack Channel Regulates Anxiety-Like Behaviors via Basolateral Amygdala Glutamatergic Projections to Ventral Hippocampus.

Anxiety disorders are a series of mental disorders characterized by anxiety and fear, but the molecular basis of these disorders remains unclear. In the present study, we find that the global Slack KO male mice exhibit anxious behaviors, whereas the Slack Y777H male mice manifest anxiolytic behaviors. The expression of Slack channels is rich in basolateral amygdala (BLA) glutamatergic neurons and downregulated in chronic corticosterone-treated mice. In addition, electrophysiological data show enhanced excitability of BLA glutamatergic neurons in the Slack KO mice and decreased excitability of these neurons in the Slack Y777H mice. Furthermore, the Slack channel deletion in BLA glutamatergic neurons is sufficient to result in enhanced avoidance behaviors, whereas Kcnt1 gene expression in the BLA or BLA-ventral hippocampus (vHPC) glutamatergic projections reverses anxious behaviors of the Slack KO mice. Our study identifies the role of the Slack channel in controlling anxious behaviors by decreasing the excitability of BLA-vHPC glutamatergic projections, providing a potential target for anxiolytic therapies.SIGNIFICANCE STATEMENT Anxiety disorders are a series of mental disorders characterized by anxiety and fear, but the molecular basis of these disorders remains unclear. Here, we examined the behaviors of loss- and gain-of-function of Slack channel mice in elevated plus maze and open field tests and found the anxiolytic role of the Slack channel. By altering the Slack channel expression in the specific neuronal circuit, we demonstrated that the Slack channel played its anxiolytic role by decreasing the excitability of BLA-vHPC glutamatergic projections. Our data reveal the role of the Slack channel in the regulation of anxiety, which may provide a potential molecular target for anxiolytic therapies.

CDBN-YGXZ, a Novel Small-Molecule Drug, Shows Efficacy against Clostridioides difficile Infection and Recurrence in Mouse and Hamster Infection Models.

Clostridioides difficile infection (CDI) causes severe diarrhea and colitis, leading to significant morbidity, mortality, and high medical costs worldwide. Oral vancomycin, a first-line treatment for CDI, is associated with a high risk of recurrence, necessitating novel therapies for primary and recurrent CDI. A novel small-molecule compound, CDBN-YGXZ, was synthesized by modifying the benzene ring of nitazoxanide with lauric acid. The mechanism of action of CDBN-YGXZ was validated using a pyruvate:ferredoxin/flavodoxin oxidoreductase (PFOR) inhibition assay. The efficacy of CDBN-YGXZ was evaluated using the MIC test and CDI infection model in mice and hamsters. Furthermore, metagenomics was used to reveal the underlying reasons for the effective reduction or prevention of CDI after CDBN-YGXZ treatment. The inhibitory activity against PFOR induced by CDBN-YGXZ. MIC tests showed that the in vitro activity of CDBN-YGXZ against C. difficile ranging from 0.1 to 1.5 µg/mL. In the mouse and hamster CDI models, CDBN-YGXZ provided protection during both treatment and relapse, while vancomycin treatment resulted in severe relapse and significant clinical scores. Compared with global effects on the indigenous gut microbiota induced by vancomycin, CDBN-YGXZ treatment had a mild influence on gut microbes, thus resulting in the disappearance or reduction of CDI recurrence. CDBN-YGXZ displayed potent activity against C. difficile in vitro and in vivo, reducing or preventing relapse in infected animals, which could merit further development as a potential drug candidate for treating CDI.

Correlation analysis between morphologic characteristics of the thoracolumbar basivertebral foramen and Kummell's disease in patients with osteoporosis using imaging techniques.

BACKGROUND: The aging of the population is a social problem faced by many countries in the world. With the increase in the elderly population, the number of patients with Kummell's disease is also gradually increasing. No study has demonstrated that Kummell's disease has a clear correlation with the foramen of a vertebrobasilar vein. OBJECTIVES: The research was conducted to describe and evaluate the morphological characteristics of a basivertebral foramen in patients with osteoporosis and Kummell's disease by CT; to infer whether the specific morphological characteristics of basivertebral foramen may be one of the risk factors of Kummell's disease; to provide clinical suggestions for the treatment of Kummell's disease. DESIGN: Retrospective analysis from January 2020 to December 2021 on 83 patients with 83 vertebral bodies (T8-L5) diagnosed with senile osteoporosis and Kummell's disease hospitalized in our hospital due to chronic low back pain, including 57 women and 23 men. Group A was assigned for the following patients: the age ranged from 59 to 86 years old, with the average age of 67.30 ± 7.32 years old; the body mass index ranged from 20.01 to 29.46 kg/m2, with the average body mass index of 23.51 ± 3.03 kg/m2.Group B was assigned for the following patients: 83 patients diagnosed with senile osteoporosis in our outpatient department from January 2020 to December 2021, including 41 males and 42 females; the age ranged from 60 to 85 years, with an average age of 68.52 ± 4.68 years old; the height to weight ratio met the normal reference standard (except 20% above or 10% below the standard weight). Through the lanwon PACS imaging system, the related parameters of the vertebrobasilar foramen in patients with osteoporosis and Kummell's disease were measured to evaluate and analyze the correlation between the morphological characteristics of the vertebrobasilar foramen in patients with osteoporosis and Kummell's disease. RESULTS: In patients with osteoporosis, the distribution of incidence rate of Kummell's disease in the spine was consistent with that of osteoporotic compression fractures. Sagittal view of the vertebral body on CT scan and the triangular-shaped, trapezoidal-shaped, and irregular-shaped basivertebral foramen in group A accounted for 18%,57%,and 36%,respectively. In group B, triangular-shaped, trapezoidal-shaped, and irregular-shaped foramen accounted for 51%,17%,and 26%,respectively.The distribution of triangular-shaped, trapezoidal-shaped, and irregular-shaped foramen was compared between groups A and B, and the difference was recorded as statistically significant (P < 0.05). Additionally, the difference in the distribution of triangular-shaped, trapezoidal-shaped, and irregular-shaped foramen in group A was found statistically significant (P < 0.05),while that of Group B was found statistically insignificant (P > 0.05).On a horizontal CT scan of the vertebra of group A, triangles, trapezoids, and irregularities accounted for 28%, 26%, and 47%, respectively. In group B, triangles,trapezoids,and irregularities accounted for 31%, 37%, and 30%, respectively. The difference in the distribution of the triangular-shaped and trapezoidal-shaped foramen in groups A and B was statistically insignificant (P > 0.05), while that of irregular-shaped was statistically significant (P < 0.05). Additionally, there was no statistical significance (P > 0.05) in the difference in the morphological distribution of triangular-shaped and trapezoidal-shaped foramen in group A, while that of irregular-shaped was found to be statistically significant (P < 0.05). Further, the difference in the morphological distribution of triangular-shaped, trapezoidal-shaped, and irregular-shaped foramen in group B was not statistically significant (P > 0.05).In general, about 8% of the vertebral body of BF has an osseous septum. In group A, 97% are single-holed while the remaining 3% are porous; in group B, those with single holes accounted for 76%, while the remaining 24% are porous. In groups A and B, the difference in the morphological distribution of single-holed and multi-holed T8, T11, T12, L1, L2, L4, and L5 vertebral bodies was statistically significant (P < 0.05). In group A, the difference in the distribution of single-holed and multi-holed L1 and L5 vertebral bodies was statistically significant (P < 0.05). Similarly, the difference in the distribution of single-holed and multi-holed T8, T11, T12, L1, L2, and L4 basivertebral foramen was statistically significant (P < 0.05). CONCLUSIONS: In patients with osteoporosis, the incidence of vertebral Kummell's disease can be associated with the morphological characteristics of the basivertebral foramen, as observed in the CT scan. Furthermore, the vertebral body with trapezoidal-shaped and irregular-shaped basivertebral foramen and boneless septum in the foramen is highly susceptible to Kummell's disease.

Genetic and molecular characterization of determinant of six-rowed spike of barley carrying vrs1.a4.

KEY MESSAGE: Decisive role of reduced vrs1 transcript abundance in six-rowed spike of barley carrying vrs1.a4 was genetically proved and its potential causes were preliminarily analyzed. Six-rowed spike 1 (vrs1) is the major determinant of the six-rowed spike phenotype of barley (Hordeum vulgare L.). Alleles of Vrs1 have been extensively investigated. Allele vrs1.a4 in six-rowed barley is unique in that it has the same coding sequence as Vrs1.b4 in two-rowed barley. The determinant of row-type in vrs1.a4 carriers has not been experimentally identified. Here, we identified Vrs1.b4 in two-rowed accessions and vrs1.a4 in six-rowed accessions from the Qinghai-Tibet Plateau at high frequency. Genetic analyses revealed a single nuclear gene accounting for row-type alteration in these accessions. Physical mapping identified a 0.08-cM (~ 554-kb) target interval on chromosome 2H, wherein Vrs1 was the most likely candidate gene. Further analysis of Vrs1 expression in offspring of the mapping populations or different Vrs1.b4 and vrs1.a4 lines confirmed that downregulated expression of vrs1.a4 causes six-rowed spike. Regulatory sequence analysis found a single 'TA' dinucleotide deletion in vrs1.a4 carriers within a 'TA' tandem-repeat-enriched region ~ 1 kb upstream of the coding region. DNA methylation levels did not correspond to the expression difference and therefore did not affect Vrs1 expression. More evidence is needed to verify the causal link between the 'TA' deletion and the downregulated Vrs1 expression and hence the six-rowed spike phenotype.

Occurrence, Human Exposure, and Risk Assessment of Polybrominated Dibenzo-p-Dioxins and Dibenzofurans, Polychlorinated Naphthalenes, and Metals in Atmosphere Around Industrial Parks in Jiangsu, China.

Air samples were collected around industrial parks in Jiangsu, China, to allow the concentrations, profiles, and risk assessment of polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs), polychlorinated naphthalenes (PCNs), and metals to be investigated. The concentrations of ΣPBDD/Fs and ΣPCNs were 1324.26-2080.98 fg/m3 (11.35-42.57 fg I-TEQ/m3) and 10,404.9-29,322.9 fg/m3 (1.32-7.19 fg I-TEQ/ m3), respectively. The highest concentration of ΣPBDD/Fs and ΣPCNs were observed at site C. PBDD/Fs were mainly dominated by PBDFs. The main contributor to the ΣPBDD/Fs in all samples was 1,2,3,4,6,7,8-HpBDF, which accounted for 25.75%-39.4%. For PCNs, the predominating homologues were tetra-, tri- and penta-CNs, which contributed 30.7%-43.3%, 24.7%-31.0%, and 10.6%-21.6%, respectively. As for metals, the pollution of As, Mn, Cr, and Ni in most samples exceeded National Ambient Air Quality Standards of China. Assessing the risk of inhalation exposure showed that there were potential carcinogenic risks to local residents.

Concentrations, Sources, and Potential Human Health Risks of PCDD/Fs, dl-PCBs, and PAHs in Rural Atmosphere Around Chemical Plants in Jiangsu Province, China.

Concentrations and sources of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), dioxin-like polychlorinated biphenyls (dl-PCBs), and polycyclic aromatic hydrocarbons (PAHs) in a rural atmosphere near industrial zones in Jiangsu, China were determined and the associated risks were assessed. The concentrations of ΣPCDD/Fs, ΣPCBs, and ΣPAHs ranged from 11.9-57.7 pg·m-3, 0.58-2.71 pg m-3, and 11-18 ng m-3, respectively. Principal component analysis suggested that the contamination of air with PCDD/Fs and PCBs mainly originated from industrial activities and combustion processes. In contrast, the major source of PAHs was the combustion of petroleum, coal, and biomass. These data were used to estimate the exposure of the population living nearby to these persistent organic pollutants and to evaluate the non-carcinogenic and carcinogenic risks associated with their inhalation. Our study are likely to be helpful for developing and implementing regulation strategies for PCDD/Fs, dl-PCBs, and PAHs in the atmosphere around industrial and surrounding residential areas.

Role of HGF/c-Met in the treatment of colorectal cancer with liver metastasis.

The system of hepatocyte growth factor (HGF) and its receptor c-Met plays a critical role in tumor invasive growth and metastasis. The mortality rate of colorectal cancer (CRC), one of the most commonly diagnosed malignancies, is increased by it gradual development into metastasis, most frequently in the liver. Overexpression of c-Met, the protein tyrosine kinase receptor for the HCF/scatter factor, has been implicated in the progression and metastasis of human colorectal carcinoma. In this study, we aimed to investigate the role of c-Met in CRC liver metastasis and illustrate the clinical impact of regulating HGF/c-Met signaling in patients with CRC liver metastasis. We found that (I) higher levels of c-Met expression (mRNA and Protein) in CRC liver metastasis than primary CRC by assessing the patient tissue samples; (II) a positive correlation of c-Met expression with tumor stages of CRC liver metastasis, as well as c-Met expression in CRC, live metastasis concurred with regional lymph node metastasis; (III) the clinical impact of downregulation of HGF/c-Met signaling on the reduction of proliferation and invasion in CRC liver metastasis. Therefore, we demonstrate that the regulation of HGF/c-Met pathways may be a promising strategy in the treatment of patients with CRC liver metastasis.

Observation and comparison of tower vibration and underwater noise from offshore operational wind turbines in the East China Sea Bridge of Shanghai.

Underwater operational turbine noise emitted by China's first offshore wind farm in the East China Sea Bridge of Shanghai was measured and analyzed in this study. Two sensors were used in the measurement: a hydrophone recording the underwater sound and an accelerometer placed in the turbine tower detecting the tower vibrations. Measurements were performed at two different types of wind turbines: a Sinovel 3 MW SL3000 turbine and a Shanghai Electric 3.6 MW W3600 turbine. The two turbines show similar tower vibration characteristics, characterized by a number of tonal components, mainly in the low-frequency domain (30-500 Hz). The peak vibration frequencies changed with the wind speed until the turbine approached its nominal power rating. Spectral analysis of the underwater acoustic data showed that the amplitude spectra had a strong correlation with the spectra of the turbine vibration intensity level, indicating that the measured underwater noise was generated by the tower mechanical vibration.

Coastal sound-field change due to typhoon-induced sediment warming.

Typhoon induced sediment warming has been proven important to coastal sound-field change in this study. It was observed that the temperature of the bottom waters off the coast of Qingdao increased by 5 °C after the passage of typhoon Damrey in 2012. Sediment warming due to bottom-water temperature increase was calculated and the change in sediment sound speed was estimated. Transmission loss (TL) was simulated both with and without consideration of the change in sediment sound speed induced by temperature variation and results showed TL change could be >10 dB within a distance of 16 km.

[Protective effect of tadalafil against ischemia-reperfusion injury in rats].

OBJECTIVE: To investigate the protective effect of phosphodiesterase type 5 inhibitors (tadalafil) on the testis following testicular ischemia-reperfusion injury in rats. METHODS: Eighty-four healthy adult male SD rats were randomly and equally divided into groups A (sham operation), B (testicular torsion + low-dose tadalafil), C (testicular torsion + high-dose tadalafil), and D (testicular torsion + placebo). Models were established in the latter three groups by 7200 torsion of the right testis for 2 hours. The animals in groups A and B were treated by gavage with tadalafil at the dose of 0. 5 mg per kg per day, those in group C at 2 mg per kg per day, and those in group D with saline at the same dose. After 3, 7, and 14 days of treatment, the torsioned testes were harvested for evaluation of the superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the testis tissue. The pathological changes in the testis were observed under the light microscope. RESULTS: At 3, 7, and 14 days, the SOD activity was (254.46 +/- 7.43), (278.49 +/- 8.33), and (317.99 +/- 3.31) nU/mg prot in group B, and (277.12 +/- 8.80), (309.40 +/- 2.14), and (320.39 +/- 4.72) nU/mg prot in group C, all obviously higher than in D ([223.21 +/- 4.65], [231.45 +/- 4.16] and [248.28 +/- 5.74] nU/mg prot), while the MDA content was lower in the former two groups than in the latter. At 3 and 7 days, the SOD activity was significantly higher and the MDA level significantly lower in group C than in B (both P < 0.01) , while at 14 days, neither showed any remarkable differences between the two groups (P > 0.05). No obvious histopathological change was observed in the testis tissue of group A. At 3 and 7 days, pathological examination of the testis tissue revealed significant differences in the number of seminiferous epithelial layers, testicular histological score, and seminiferous tubule diameter in group B (P < 0.01), but the three indexes at 14 days in group B and at 7 days in group C exhibited no remarkable differences from those at 14 days in group A. CONCLUSION: Tadalafil can alleviate testicular ischemia-reperfusion injury following testis torsion/detorsion in a time- and dose-dependent manner.

Possible benefit of splenectomy in liver transplantation for autoimmune hepatitis.

Liver transplantation for autoimmune hepatitis (AIH) is usually successful with excellent long-term outcomes, but primary disease may recur. The recurrence of AIH is a significant cause of graft loss. This study was to analyze the effect of splenectomy in preventing AIH relapse. The clinical courses of 12 patients who had transplantation for AIH were analyzed retrospectively. All patients were subjected to transplantation for end-stage liver disease caused by chronic AIH. Based on the duration of immunosuppressive treatment before liver transplantation, simultaneous splenectomy was performed in ten patients. Two patients underwent liver transplantation without splenectomy, one of them developed recurrent AIH and died from graft failure caused by AIH relapse. However, no episode of AIH recurrence was observed in patients who had undergone simultaneous splenectomy. Splenectomy might be an option to prevent AIH relapse in some patients with high risk factors.

Overexpression of EphB2 in the basolateral amygdala is crucial for inducing visceral pain sensitization in rats subjected to water avoidance stress.

AIMS: Basolateral amygdala (BLA), as a center for stress responses and emotional regulation, is involved in visceral hypersensitivity of irritable bowel syndrome (IBS) induced by stress. In the present study, we aimed to investigate the role of EphB2 receptor (EphB2) in BLA and explore the underlying mechanisms in this process. METHODS: Visceral hypersensitivity was induced by water avoidance stress (WAS). Elevated plus maze test, forced swimming test, and sucrose preference test were applied to assess anxiety- and depression-like behaviors. Ibotenic acid or lentivirus was used to inactivate BLA in either the induction or maintenance stage of visceral hypersensitivity. The expression of protein was determined by quantitative PCR, immunofluorescence, and western blot. RESULTS: EphB2 expression was increased in BLA in WAS rats. Inactivation of BLA or downregulation of EphB2 in BLA failed to induce visceral hypersensitivity as well as anxiety-like behaviors. However, during the maintenance stage of visceral pain, visceral hypersensitivity was only partially relieved but anxiety-like behaviors were abolished by inactivation of BLA or downregulation of EphB2 in BLA. Chronic WAS increased the expression of EphB2, N-methyl-D-aspartate receptors (NMDARs), and postsynaptic density protein (PSD95) in BLA. Downregulation of EphB2 in BLA reduced NMDARs and PSD95 expression in WAS rats. However, activation of NMDARs after the knockdown of EphB2 expression still triggered visceral hypersensitivity and anxiety-like behaviors. CONCLUSIONS: Taken together, the results suggest that EphB2 in BLA plays an essential role in inducing visceral hypersensitivity. In the maintenance stage, the involvement of EphB2 is crucial but not sufficient. The increase in EphB2 induced by WAS may enhance synaptic plasticity in BLA through upregulating NMDARs, which results in IBS-like symptoms. These findings may give insight into the treatment of IBS and related psychological distress.

Paxlovid-tacrolimus drug-drug interaction caused severe diarrhea that induced combined diabetic ketoacidosis and a hyperglycemic hyperosmolar state in a kidney transplant patient: a case report.

BACKGROUND: Transplant recipients are at high risk of coronavirus disease 2019, and a timely supply of antivirals should be prioritized for those patients. Complicated drug‒drug interactions limit the use of Paxlovid (nirmatrelvir/ritonavir) coadministered with tacrolimus. Here, we report a patient with a kidney transplant who received Paxlovid and reduced-dose tacrolimus at the same time and suffered a severe tacrolimus toxicity. CASE PRESENTATION: We present a 56-year-old man of Han ethnicity with a kidney transplant who suffered from coronavirus disease 2019 twice. For the first infection, the immunosuppressants were substituted by dexamethasone when the patient used Paxlovid, and everything went well. For the second time, tacrolimus at a reduced dose concomitant with Paxlovid caused severe diarrhea, inducing combined diabetic ketoacidosis and a hyperglycemic hyperosmolar state. CONCLUSION: This case challenges the dose-adjustment strategy of managing drug‒drug interactions. We suggest that tacrolimus should be stopped when Paxlovid is applied and that corticosteroids could be a good substitution.

De novo assembly and characterization of the root transcriptome of Aegilops variabilis during an interaction with the cereal cyst nematode.

BACKGROUND: Aegilops variabilis No.1 is highly resistant to cereal cyst nematode (CCN). However, a lack of genomic information has restricted studies on CCN resistance genes in Ae. variabilis and has limited genetic applications in wheat breeding. RESULTS: Using RNA-Seq technology, we generated a root transcriptome at a sequencing depth of 4.69 gigabases of Ae. variabilis No. 1 from a pooled RNA sample. The sample contained equal amounts of RNA extracted from CCN-infected and untreated control plants at three time-points. Using the Trinity method, nearly 52,081,238 high-quality trimmed reads were assembled into a non-redundant set of 118,064 unigenes with an average length of 500 bp and an N50 of 599 bp. The total assembly was 59.09 Mb of unique transcriptome sequences with average read-depth coverage of 33.25×. In BLAST searches of our database against public databases, 66.46% (78,467) of the unigenes were annotated with gene descriptions, conserved protein domains, or gene ontology terms. Functional categorization further revealed 7,408 individual unigenes and three pathways related to plant stress resistance. CONCLUSIONS: We conducted high-resolution transcriptome profiling related to root development and the response to CCN infection in Ae. variabilis No.1. This research facilitates further studies on gene discovery and on the molecular mechanisms related to CCN resistance.

(E)-1-(5-Bromo-2-hy-droxy-phen-yl)-3-[4-(dimethyl-amino)-phen-yl]prop-2-en-1-one.

In the title compound, C(17)H(16)BrNO(2), the two benzene rings make a dihedral angle of 7.4 (3)°; the hy-droxy group links to the carbonyl group via an intra-molecular O-H⋯O hydrogen bond. In the crystal, weak C-H⋯O inter-actions link the mol-ecules into a supra-molecular chain running along the c axis.

[Acquiring laparoscopic skill for colorectal surgery: based on the experience of a colorectal surgeon].

OBJECTIVE: Laparoscopic colorectal surgery is a skill-dependent procedure. The present study aims to analyze the learning curve of a properly trained surgeon, with basic laparoscopic techniques, to become skillful in performing laparoscopic colorectal operations. METHODS: A series of non-selective, consecutive 189 cases of laparoscopic colorectal surgery were accomplished, from December 2009 to February 2012, by one surgeon with years of skilled technique in laparoscopic cholecystectomy, rich experience in assisting laparoscopic colorectal surgery, and experience of approximately 180 procedures of gastric and colorectal surgery annually. 170 out of 189 procedures were radical operations for colorectal neoplasma, including right colectomies in 28 cases, left colectomies in 5 cases, sigmoidectomies in 28 cases, high Dixon procedures in 45 cases, low Dixon (total mesorectal excision, TME) procedures in 41 cases and Miles procedure in 23 cases. 19 other patients underwent combined procedures for multi-primary tumors or inflammatory enteritis. All these procedures were analyzed according to time span (the earlier half and later half) in respect to length of surgery, intraoperative blood loss, number of lymph nodes retrieved, intraoperative events and postoperative complications. RESULTS: For radical right colectomy, the D2 dissection conducted in the earlier phase (n = 8) had the similar length of surgery, more blood loss and less LN retrieval, compared with the D3 dissection conducted in recent phase (n = 20). The earlier performed high Dixon procedures (n = 22) consumed longer time than the later procedures (n = 23) consumed, but with similar blood loss and LN retrieval. Low Dixon (TME) procedures showed significant differences in length of surgery and blood loss relative to time span. Recently performed simoidectomy and Miles procedures showed a trend of shorter time consumed compared with earlier performed procedures. Conversion ratio to open surgery was 1.05%. Adverse effects occurred in 8 cases of surgeries, including intestinal injury (3/189), insufficient distal margin (2/189), intraoperative bleeding (2/189) and vaginal injury (1/76). There was no operative death. Chief complications included urinary retention 5.82%, ileus 4.76%, anastomotic leak 4.24%, perineal infection 23.08% (6/26), wound dehiscence 2.65%, gastrointestinal bleeding 1.59%, peritoneal infection 1.06%. Surgery for distal rectum tended to have more complications, such as urinary retention, anastomotic leak and perineal infection. The later performed low Dixon procedures produced insignificantly fewer anastomotic leaks than those in the earlier phase. CONCLUSIONS: For a trained surgeon with basic laparoscopic techniques, there are at least 15 - 25 cases of different procedures needed for him/her to become skilled to perform laparoscopic surgery. The learning curve should also depend on the annual number of colorectal surgeries.

KC-180-2 Exerts Anti-SCLC Effects via Dual Inhibition of Tubulin Polymerization and Src Signaling.

In this study, a series of N-benzyl-2-(5-phenylpyridin-2-yl) acetamide-based derivatives were successfully designed and synthesized as anti-cancer agents. KC-180-2 was screened as a potentially leading compound with dual mechanisms of action: Src signaling and tubulin polymerization inhibition. It efficiently suppressed the proliferation of five cancer cell lines (MDA-MB-231, H446, SKOV-3, HepG2, and HT29), with IC50 values ranging from 5 to 188 nM, especially small-cell lung cancer (SCLC) cells (IC50, 5 nM). Correspondingly, it exerted a significant therapeutic effect on the H446 small-cell lung cancer xenograft model, significantly reducing the volume of tumors without obvious toxicity. Mechanistically, this compound significantly inhibited the polymerization of purified tubulin in vitro, inducing G2/M cell cycle arrest and binding to the kinase catalytic domain of the Src protein, which reduced the phosphorylation of Src. Thus, KC-180-2 is a potential lead compound for the further development of a new anti-tumor drug against SCLC.

A novel gut-restricted RIPK1 inhibitor, SZ-15, ameliorates DSS-induced ulcerative colitis.

As a key mediator of cell death and inflammation, receptor-interacting protein kinase 1 (RIPK1) responds to a broad set of inflammatory and pro-death stimuli in human diseases. Inhibitors targeting RIPK1 are being investigated for the treatment of a wide range of human diseases, including ulcerative colitis. In the present study, we designed, synthesized, and investigated the anti-necroptosis and RIPK1-inhibition effects of SZ-15-a symmetrical high-molecular-weight (>500 Da) compound. SZ-15 effectively inhibited necroptosis in U937 and HT-29 cells at concentrations of 1 nM and 10 nM, respectively, and SZ-15 at a concentration of 10 nM almost completely blocked RIPK1, RIPK3, and mixed-lineage kinase domain-like (MLKL) protein phosphorylation induced by necrosis inducers. SZ-15 suppressed the pro-necroptosis function of RIPK1 by downregulating the mRNA expression of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6. The activities of SZ-15 were effectively restricted to the gut: The percent recovery of the parent form of SZ-15 in mouse feces was 85.75%. Nevertheless, SZ-15 was effectively absorbed and detected in colon tissues after 1 h at a concentration of 3335 ± 868 ng/g, indicating that membrane permeability was maintained. SZ-15 alleviated dextran sulfate sodium (DSS)-induced ulcerative colitis in vivo by decreasing TNF-α, IL-1ß, IL-22, and IL-6 mRNA expression in colonic tissues. Our preclinical study describes a novel gut-restricted RIPK1 inhibitor that shows great potential for use in the clinical treatment of ulcerative colitis.

Starch granule-associated proteins of hull-less barley (Hordeum vulgare L.) from the Qinghai-Tibet Plateau in China.

BACKGROUND: The starch granule-associated proteins (SGAPs) are the minor components of the starch granules and a majority of them are believed to be starch biosynthetic enzymes. The Qinghai-Tibet Plateau in China, one of the centres of origin of cultivated barley, is abundant in hull-less barley resources which exhibit high polymorphism in SGAPs. RESULTS: The SGAPs of hull-less barley from Qinghai-Tibet Plateau were analysed by one-dimensional (1-D) SDS-PAGE, 2-D PAGE and ESI-Q-TOF MS/MS. In the 1-D SDS-PAGE gel, four proteins including a 80 kDa starch synthase, actin, actin 4 and ATP synthase ß-subunit were identified as novel SGAPs. A total of six different bands were identified as starch granule-bound starch synthase I (GBSSI) and the segregation of the novel GBSSI bands in F(1) and F(2) seeds derived from yf127 × yf70 was in accordance with Mendel's law. In the 2-D PAGE gel, 92 spots were identified as 42 protein species which could be classified into 15 functional groups. Thirteen protein species were identified as SGAPs for the first time and multiple spots were identified as GBSSI. CONCLUSION: This study revealed novel SGAPs in hull-less barley from the Qinghai-Tibet Plateau in China and these will be significant in further studies of starch biosynthesis in barley.

Computed tomography features of COVID-19 in children: A systematic review and meta-analysis.

BACKGROUND: There are few reports on the chest computed tomography (CT) imaging features of children with coronavirus disease 2019 (COVID-19), and most reports involve small sample sizes. OBJECTIVES: To systematically analyze the chest CT imaging features of children with COVID-19 and provide references for clinical practice. DATA SOURCES: We searched PubMed, Web of Science, and Embase; data published by Johns Hopkins University; and Chinese databases CNKI, Wanfang, and Chongqing Weipu. METHODS: Reports on chest CT imaging features of children with COVID-19 from January 1, 2020 to August 10, 2020, were analyzed retrospectively and a meta-analysis carried out using Stata12.0 software. RESULTS: Thirty-seven articles (1747 children) were included in this study. The heterogeneity of meta-analysis results ranged from 0% to 90.5%. The overall rate of abnormal lung CT findings was 63.2% (95% confidence interval [CI]: 55.8%-70.6%), with a rate of 61.0% (95% CI: 50.8%-71.2%) in China and 67.8% (95% CI: 57.1%-78.4%) in the rest of the world in the subgroup analysis. The incidence of ground-glass opacities was 39.5% (95% CI: 30.7%-48.3%), multiple lung lobe lesions was 65.1% (95% CI: 55.1%-67.9%), and bilateral lung lesions was 61.5% (95% CI: 58.8%-72.2%). Other imaging features included nodules (25.7%), patchy shadows (36.8%), halo sign (24.8%), consolidation (24.1%), air bronchogram signs (11.2%), cord-like shadows (9.7%), crazy-paving pattern (6.1%), and pleural effusion (9.1%). Two articles reported 3 cases of white lung, another reported 2 cases of pneumothorax, and another 1 case of bullae. CONCLUSIONS: The lung CT results of children with COVID-19 are usually normal or slightly atypical. The lung lesions of COVID-19 pediatric patients mostly involve both lungs or multiple lobes, and the common manifestations are patchy shadows, ground-glass opacities, consolidation, partial air bronchogram signs, nodules, and halo signs; white lung, pleural effusion, and paving stone signs are rare. Therefore, chest CT has limited value as a screening tool for children with COVID-19 and can only be used as an auxiliary assessment tool.