Near-atomic-resolution cryo-EM analysis of the Salmonella T3S injectisome basal body.

The type III secretion (T3S) injectisome is a specialized protein nanomachine that is critical for the pathogenicity of many Gram-negative bacteria, including purveyors of plague, typhoid fever, whooping cough, sexually transmitted infections and major nosocomial infections. This syringe-shaped 3.5-MDa macromolecular assembly spans both bacterial membranes and that of the infected host cell. The internal channel formed by the injectisome allows for the direct delivery of partially unfolded virulence effectors into the host cytoplasm. The structural foundation of the injectisome is the basal body, a molecular lock-nut structure composed predominantly of three proteins that form highly oligomerized concentric rings spanning the inner and outer membranes. Here we present the structure of the prototypical Salmonella enterica serovar Typhimurium pathogenicity island 1 basal body, determined using single-particle cryo-electron microscopy, with the inner-membrane-ring and outer-membrane-ring oligomers defined at 4.3 Å and 3.6 Å resolution, respectively. This work presents the first, to our knowledge, high-resolution structural characterization of the major components of the basal body in the assembled state, including that of the widespread class of outer-membrane portals known as secretins.

Does neoadjuvant therapy increase the incidence of anastomotic leakage after anterior resection for mid and low rectal cancer? A systematic review and meta-analysis.

AIM: The aim was to evaluate the association of neoadjuvant therapy with increases in the incidence of anastomotic leakage (AL) after middle and low rectal anterior resection. METHOD: The electronic databases of PubMed, Web of Science, Scopus and Ovid were searched between 1980 and 2015. The random effects model was used to model the pooled data to determine the odds ratio with 95% confidence interval. Heterogeneity was evaluated using the Q test and I2 statistics. Subgroup, sensitivity and meta-regression analysis was conducted to explore heterogeneity. RESULTS: Neoadjuvant therapy was not shown to increase the incidence of postoperative AL as demonstrated by an OR of 1.16 [95% CI 0.99-1.36; P = 0.07 (random effects model)]. The subgroup analysis of neoadjuvant radiotherapy using the random effects model suggested that it did not increase the rate of postoperative AL (OR = 1.24, 95% CI 0.97-1.58; P = 0.08). The subgroup analysis of neoadjuvant chemoradiotherapy indicated that the rate of postoperative AL again did not increase with an OR = 1.06 [95% CI 0.86-1.30; P = 0.59 (random effects model)]. The interval to surgery after neoadjuvant therapy and preoperative radiotherapy (short or long course) was not associated with an increased incidence of postoperative AL. CONCLUSION: Neoadjuvant therapy does not appear to increase the incidence of postoperative AL after anterior resection for mid and low rectal cancer. In addition, neither the interval to surgery after neoadjuvant therapy nor the radiotherapy regimen increases the rate of postoperative AL.

[Intraperitoneal chemotherapy for colorectal cancer peritoneal metastasis].

Peritoneal metastasis is one of the common site of colorectal cancer metastasis and associated with a poor prognosis. The core strategy for colorectal cancer peritoneal metastasis primarily revolves around a comprehensive treatment approach with cytoreductive surgery and systemic chemotherapy as the mainstay, supplemented by intraperitoneal chemotherapy. As an important supplement to treatment, intraperitoneal chemotherapy has broad application prospects. The main modalities are hyperthermic intraperitoneal chemotherapy (HIPEC), neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), early postoperative intraperitoneal chemotherapy (EPIC), sequential postoperative intraperitoneal chemotherapy (SPIC), normothermic intraperitoneal chemotherapy (NIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC). To promote the standardized application of intraperitoneal chemotherapy, further research on the mechanisms underlying peritoneal metastasis of colorectal cancer, selection of effective intraperitoneal chemotherapy agents, determination of optimal timing and administration protocols, exploration of the feasibility of sequential intraperitoneal chemotherapy and conduction of valuable basic and clinical research are currently needed. This paper will review the development and origins of intraperitoneal chemotherapy, treatment modalities, as well as the current application status and prospects of various treatment approaches in the context of peritoneal metastasis of colorectal cancer.

[Establishment of treatment center for peritoneal metastasis in colorectal cancer].

The prognosis of patients with peritoneal metastasis from colorectal cancer is poor. At present, the comprehensive treatment system based on cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has significantly improved the survival of these patients. However, CRS and HIPEC have strict indications, high procedural difficulty, and high morbidity and mortality. If CRS+HIPEC is performed in an inexperienced center, overall survival and quality of life of patients may bo compromised. The establishment of specialized diagnosis and treatment centers can provide a guarantee for standardized clinical diagnosis and treatment. In this review, we first introduced the necessity of establishing a colorectal cancer peritoneal metastasis treatment center and the construction situation of the diagnosis and treatment center for peritoneal surface malignancies at home and abroad. Then we focused on introducing our construction experience of the colorectal peritoneal metastasis treatment center, and emphasized that the construction of the center must be done well in two aspects: firstly, the clinical optimization should be realized and the specialization of the whole workflow should be strengthened; secondly, we should ensure the quality of patient care and the rights, well-being and health of every patient.

Kaposi's sarcoma after steroid therapy for pemphigus foliaceus.

A patient with pemphigus foliaceus, derived from pemphigus erythematosus, developed Kaposi's sarcoma characterized by wide-spread skin nodules on the extremities after 5-month treatment with large doses of prednisone. The patient died one year later. We conclude that the immunosuppressive treatment with prolonged large doses of prednisone is attributable to the impairment of cellular immunity and the evolution of Kaposi's sarcoma.

Near-diffraction-limited diode laser arrays by wavelength beam combining.

We demonstrate 35 W output peak power with M2 approximately 1.35 in both dimensions from a 100 element, 100 microm pitch slab-coupled optical waveguide laser diode array using wavelength beam combining.

The effect of two alkylphenols on vitellogenin levels in male carp.

Nonylphenol and octylphenol, the major biodegradation products of nonionic surfactants, are among the increasing number of widely used industrial chemicals that are recognized as endocrine disrupters. In this study, nonylphenol and octylphenol were administered to male carp by injection, feeding and immersion, and a validated enzyme-linked immunosorbent assay (ELISA) was used to monitor the plasma levels of the yolk precursor vitellogenin over time. In injection and feeding experiments, vitellogenin levels increased significantly after 14 days. After immersion for 14 and 28 days, respectively, significantly higher concentrations of plasma vitellogenin were detected in male carp exposed to 4 microg/L nonylphenol and octylphenol. When transferred to clean water, the elevated plasma vitellogenin levels in carp exposed to 4 microg/L octylphenol for 42 days returned to control levels within 28 days.