Cancer stem cells (CSCs) are inherently resistant to chemotherapy, and CSCs in chemotherapy-failed recurrent tumors are enriched; however, the cellular origin of chemotherapy-induced CSC enrichment ...remains unclear. Communication with stromal fibroblasts may induce cancer cell dedifferentiation into CSCs through secreted factors. We recently demonstrated that fibroblast-derived exosomes promote chemoresistance in colorectal cancer (CRC). Here, we report that fibroblasts confer CRC chemoresistance via exosome-induced reprogramming (dedifferentiation) of bulk CRC cells to phenotypic and functional CSCs. At the molecular level, we provided evidence that the major reprogramming regulators in fibroblast-exosomes are Wnts. Exosomal Wnts were found to increase Wnt activity and drug resistance in differentiated CRC cells, and inhibiting Wnt release diminished this effect in vitro and in vivo. Together, our results indicate that exosomal Wnts derived from fibroblasts could induce the dedifferentiation of cancer cells to promote chemoresistance in CRC, and suggest that interfering with exosomal Wnt signaling may help to improve chemosensitivity and the therapeutic window.
We investigated 10 naturally ventilated schools in Shanghai, in winter. Pupils (13-14 years) in 30 classes received a questionnaire, 1414 participated (99%). Classroom temperatures were 13-21 degrees ...C (mean 17 degrees C), relative air humidity was 36-82% (mean 56%). The air exchange rate was 2.9-29.4 ac/h (mean 9.1), because of window opening. Mean CO2 exceeded 1000 ppm in 45% of the classrooms. NO2 levels were 33-85 microg/m3 indoors, and 45-80 microg/m3 outdoors. Ozone were 1-9 microg/m3 indoors and 17-28 microg/m3 outdoors. In total, 8.9% had doctors' diagnosed asthma, 3.1% wheeze, 23.0% daytime breathlessness, 2.4% current asthma, and 2.3% asthma medication. Multiple logistic regression was applied. Observed indoor molds was associated with asthma attacks odds ratio (OR) = 2.40: P < 0.05. Indoor temperature was associated with daytime breathlessness (OR = 1.26 for 1 C; P < 0.001), and indoor CO2 with current asthma (OR = 1.18 for 100 ppm; P < 0.01) and asthma medication (OR = 1.15 for 100 ppm; P < 0.05). Indoor NO2 was associated with current asthma (OR = 1.51 for 10 microg/m3; P < 0.01) and asthma medication (OR = 1.45 for 10 microg/m3; P < 0.01). Outdoor NO2 was associated with current asthma (OR = 1.44 for 10 microg/m3; P < 0.05). Indoor and outdoor ozone was negatively associated with daytime breathlessness. In conclusion, asthma symptoms among pupils in Shanghai can be influenced by lack of ventilation and outdoor air pollution from traffic. Practical Implications Most urban schools in Asia are naturally ventilated buildings, often situated in areas with heavy ambient air pollution from industry or traffic. The classes are large, and window opening is the only way to remove indoor pollutants, but this results in increased exposure to outdoor air pollution. There is a clear need to improve the indoor environment in these schools. Building dampness and indoor mold growth should be avoided, and the concept of mechanical ventilation should be introduced. City planning aiming to situate new schools away from roads with heavy traffic should be considered.
The molecular characterization of cytogenetic abnormalities has not only provided insights into the mechanisms of leukemogenesis but also led to the establishment of new treatment strategies ...targeting these abnormalities and thereby further improve the prognosis of patients. We analyzed the prognosis of 1091 Chinese patients with newly diagnosed acute lymphoblastic leukemia (ALL) and explored the prognostic impacts of a large number of cytogenetic/molecular abnormalities. It was demonstrated that, in both B- and T-ALL settings, the prognosis was negatively correlated to the age as reported to date. For childhood T-ALL patients, it was also documented that the HOX11 expression represented a favorable prognostic factor as it was in adult ones. We identified CRLF2 overexpression as an intermediate-risk marker and Ik6 variant of IKZF1 gene as a high-risk one when stratifying pediatric B-ALL cases according to cytogenetic/molecular risks. We also found that Ik6 variant and CRLF2 overexpression had an important role in dictating the prognosis of Ph-negative patients, which may be useful markers in guiding the treatment of ALL in the future, with tyrosine kinase inhibitors on the other hand reversing the fate of Ph-positive ALL patients.
Globally, 296 million people are infected with hepatitis B virus (HBV), and approximately one million people die annually from HBV-related causes, including liver cancer. Although there is a ...preventative vaccine and antiviral therapies suppressing HBV replication, there is no cure. Intensive efforts are under way to develop curative HBV therapies. Currently, only a few biomarkers are available for monitoring or predicting HBV disease progression and treatment response. As new therapies become available, new biomarkers to monitor viral and host responses are urgently needed. In October 2020, the International Coalition to Eliminate Hepatitis B Virus (ICE-HBV) held a virtual and interactive workshop on HBV biomarkers endorsed by the International HBV Meeting. Various stakeholders from academia, clinical practice and the pharmaceutical industry, with complementary expertise, presented and participated in panel discussions. The clinical utility of both classic and emerging viral and immunological serum biomarkers with respect to the course of infection, disease progression, and response to current and emerging treatments was appraised. The latest advances were discussed, and knowledge gaps in understanding and interpretation of HBV biomarkers were identified. This Roadmap summarizes the strengths, weaknesses, opportunities and challenges of HBV biomarkers.
Chinese herbal medicine Jinlianqingre Effervescent Tablets (JET) are the recommended control measure for uncomplicated hand, foot, and mouth disease (HFMD) by the Ministry of Health of China. ...However, high-quality evidence to support this recommendation is limited. A total of 288 patients ranging in age from 1 to 13 years were randomly assigned to JET in combination with conventional therapy (mainly including the reduction of temperature by applying physical cooling paste or warm bathing), or conventional therapy with placebo group for 7 days. The objective was to test the hypothesis that JET combination therapy is more effective than conventional therapy for uncomplicated HFMD. A randomized, double-blind, placebo-controlled trial was designed. Our study showed that, compared with conventional therapy, the median time to fever resolution was significantly shorter in the JET combination therapy (8 vs. 80 h;
p
< 0.0001); the risk of fever resolution increased in the JET combination therapy hazard ratio, 19.8; 95 % confidence interval (CI), 12.8 to 30.7; the median healing time of rash or oral ulcer was significantly shorter in the JET combination therapy (14 vs. 74 h;
p
< 0.0001); and the median symptom score for skin or oral mucosa lesions improved more rapidly in the JET combination therapy during the follow-up period. The median duration of hospital stay was 6 days in the JET combination therapy and 7 days in the conventional therapy (
p
< 0.0001). No significant adverse events and complications were found in both groups. The addition of JET to conventional therapy reduced fever clearance time, healing time of skin or oral mucosa lesions, and duration of hospital stay in children with uncomplicated HFMD.
The unique eco-environment of the Qinghai–Tibet Plateau breeds abundant microbial resources. In this research,
Bacillus amyloliquefaciens
GL18, isolated from the rhizosphere of
Kobresia myosuroides
...from an alpine meadow, and the antagonistic activity, bacteriostatic hydrolase activity, and low temperature, salt, and drought resistance of it were determined and analysed. The seedlings of
Avena sativa
were root-irrigated using bacteria suspensions (cell concentration 1 × 10
7
cfu/mL) of GL18, and the growth-promoting effect of GL18 on it was determined under cold, salt and drought stress, respectively. The whole genome of GL18 was sequenced, and its functional genes were analysed. GL18 presented significant antagonistic activity to
Fusarium graminearum
,
Fusarium acuminatum
,
Fusarium oxysporum
and
Aspergillus niger
(inhibition zone diameter > 17 mm). Transparent zones formed on four hydrolase detection media, indicating that GL18 secreted cellulase, protease, pectinase and β-1,3-glucanase. GL18 tolerated conditions of 10 °C, 11% NaCl and 15% PEG-6000, presenting cold, salt and drought resistance. GL18 improved the cold, salt and drought tolerance of
A. sativa
and it showed significant growth effects under different stress. The total length of the GL18 genome was 3,915,550 bp, and the number of coding DNA sequence was 3726. Compared with the clusters of orthologous groups of proteins, gene ontology and kyoto encyclopedia of genes and genomes databases, 3088, 2869 and 2357 functional genes were annotated, respectively. GL18 contained gene clusters related to antibacterial substances, functional genes related to the synthesis of plant growth-promoting substances, and encoding genes related to stress resistance. This study identified an excellent
Bacillus
strain and provided a theoretical basis for improving stress resistance and promoting the growth of herbages under abiotic stress.
The objective of this review was to systematically assess the effect of thoracic epidural analgesia (TEA) vs. systemic analgesia (SA) on the recovery of gastrointestinal (GI) function in patients ...following GI surgery.
We performed a comprehensive literature search to identify randomized controlled trials of adult patients undergoing GI surgery, comparing the effect of two postoperative analgesia regimens. Patients postoperatively receiving local anesthesia‐based TEA with or without opioids were compared to patients receiving opioid‐based SA. The outcomes considered were times to GI function recovery, GI complications, and specific side effects.
Twelve studies with 331 patients in the TEA group and 319 in the SA group were included. Compared to SA, TEA improved the GI recovery after GI procedures by shortening the time to first passage of flatus by 31.3 h, 95% confidence intervals (CIs): −33.2 to −29.4, P < 0.01; and shortening the time to first passage of stool by 24.1 h, 95% CIs: −27.2 to −20.9, P < 0.001. There was no difference between the groups in the incidence of anastomotic leakage and ileus. The occurrence of postoperative hypotension was relatively higher in the TEA group, risk ratio: 7.9, 95% CIs: 2.4 to 26.5, P = 0.001; other side effects (such as pruritus and vomiting) were similar in the two groups.
There is evidence that TEA (compared to SA) improves the recovery of GI function after GI procedures without any increased risk of GI complications. To further confirm these effects, larger, better quality randomized controlled trials with standard outcome measurements are needed.
Molecular dynamics simulations have been conducted to find out the cohesion property, tensile strength, and dislocation evolution of several Cu–Fe interfaces. It is found that Cu1‾11‾/Fe(110)-KS and ...Cu(1‾11‾)/Fe(110)-NW interfaces are not only energetically favorable with lower interface energies, but also have higher strength than Cu–Fe interfaces with other interface orientations. Simulations also reveal that the formation of Cu–Fe interfaces has an important effect to increase the tensile strength of Cu under tensile loading along the directions parallel to the interface due to the block of the dislocation movement by the interface. On the contrary, the tensile strength of the Cu–Fe interfaces is smaller than that of Cu along the direction perpendicular to the interface as a result of the weak interface cohesion. The simulated results are in good agreement with experimental observations in the literature, and could provide a deep understanding of mechanical property and dislocation evolution of Cu–Fe interfaces.
•Interface energy and work of separation of Cu-Fe interfaces are derived through MD simulation.•Cu(1¯11¯)/Fe(110)-KS and Cu(1¯11¯)/Fe(110)-NW interfaces are energetically favorable with higher strength.•Cu-Fe interfaces increase tensile strength of Cu under loading parallel to the interface.•Cu-Fe interfaces decrease tensile strength of Cu under loading perpendicular to the interface.•Mechanism of dislocation evolution of Cu-Fe interfaces is revealed by the Cu-Fe potential.
The main purpose of this investigation was to identify microstructure and cyclic deformation behavior of a 3D-printed Ti–6Al–4V alloy via selective electron beam melting (SEBM). Abundant orientated ...α-lamellae were present in the prior columnar β grains along the building direction. Four distinct high-angle α/α grain boundaries were detected as stipulated by the Burgers orientation relationship in the β→α phase transformation at a relatively slow cooling rate during SEBM, including the unique low-energy prismatic/basal (PB) grain boundaries with a misorientation angle of 90° in the 3D-printed Ti–6Al–4V alloy. The alloy exhibited superior strength and adequate ductility, along with a certain extent of strain-rate sensitivity. Cyclic stabilization largely sustained, while cyclic softening occurred at higher strain amplitudes. Although fatigue life could be described by Smith, Watson and Topper (SWT) model, it would be better predicted via a total strain energy-based model. Crack initiation occurred from near-surface defects of entrapped gas pores or residual unmelted zones, and crack propagation was characterized by typical fatigue striations. The results obtained would help promote the safe and reliable applications of 3D-printed titanium components.
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•A superior strength along with sufficient ductility is achieved via 3D printing.•Abundant α lamellae are present and positioned in the prior columnar β grains.•Distinct α/α grain boundaries are detected in the β.→α phase transformation.•Cyclic stabilization retains despite cyclic softening at higher strain amplitudes.•Fatigue life can be well predicted via a total strain energy-based approach.
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