Recurrence rates of diabetic foot ulcers vary widely in the published literature. The aim of this systematic review is to estimate recurrence rates of diabetic foot ulcers. We did a PubMed search and ...performed a review of reference lists for studies reporting recurrence of diabetic foot ulcers. The weighted relative risk (RR) and corresponding 95% confidence interval (CI) for recurrence was estimated. Forty‐nine studies reporting recurrence of diabetic foot ulcers were included. A pooled estimate for recurrence rate was 22.1% per person‐year (py) (95% CI, 19.0‐25.2%). Recurrence rate was 24.9% per py in Europe (95% CI, 20.0%‐29.7%), 17.8% per py in North America (95% CI, 12.7%‐22.9%), 16.9% per py in Africa (95% CI, 4.7%‐29.0%), and 17.0% per py in Asia (95% CI, 11.1%‐23.0%). Turkey had the highest recurrence rate of 44.4% per py (95% CI, 24.9%‐63.9%), and Bangladesh had the lowest of 4.3% per py (95% CI, 2.3%‐6.3%). Recurrence rates of diabetic foot ulcers before 2002, between 2002 and 2008, and after 2008 were 22.2% per py (95% CI, 17.6%‐26.8%), 21.9% per py (95% CI, 17.0%‐26.8%), and 21.8% per py (95% CI, 16.3%‐27.2%), respectively. Recurrence rates of diabetic foot ulcers are high. Recurrence rates vary widely in different regions and have decreased recently. More attention towards recurrence of diabetic foot ulcers is urgently required.
Ubiquitin‐specific protease 22 (USP22) is a member of the “death‐from‐cancer” signature, which plays a key role in cancer progression. Previous evidence has shown that USP22 is overexpressed and ...correlates with poor prognosis in glioma. The effect and mechanism of USP22 in glioma malignancy, especially cancer stemness, remain elusive. Herein, we find USP22 is more enriched in stem‐like tumorspheres than differentiated glioma cells. USP22 knockdown inhibits cancer stemness in glioma cell lines. With a cell‐penetrating TAT‐tag protein, B cell‐specific Moloney murine leukemia virus integration site 1 (BMI1), a robust glioma stem‐cell marker, is found to mediate the effect of USP22 on glioma stemness. By immunofluorescence, USP22 and BMI1 are found to share similar intranuclear expression in glioma cells. By analysis with immunohistochemistry and bioinformatics, USP22 is found to positively correlate with BMI1 at the post‐translational level only rather than at the transcriptional level. By immunoprecipitation and in vivo deubiquitination assay, USP22 is found to interact with and deubiquitinate BMI1 for protein stabilization. Microarray analysis shows that USP22 and BMI1 mutually regulate a series of genes involved in glioma stemness such as POSTN, HEY2, PDGFRA and ATF3. In vivo study with nude mice confirms the role of USP22 in promoting glioma tumorigenesis by regulating BMI1. All these findings indicate USP22 as a novel deubiquitinase of BMI1 in glioma. We propose a working model of the USP22‐BMI1 axis, which promotes glioma stemness and tumorigenesis through oncogenic activation. Thus, targeting USP22 might be an effective strategy to treat glioma especially in those with elevated BMI1 expression.
USP22 is a cancer stem‐cell marker in glioma. USP22 is a novel deubiquitinase of BMI1, which is required for BMI1 post‐translational stabilization in glioma. The USP22‐BMI1 axis promotes glioma stemness and tumorigenesis through oncogenic activation.
B-Myb has received considerable attention for its critical tumorigenic function of supporting DNA repair. However, its modulatory effects on chemotherapy and immunotherapy have rarely been reported ...in colorectal cancer. Bortezomib (BTZ) is a novel compound with chemotherapeutic and immunotherapeutic effects, but it fails to work in colorectal cancer with high B-Myb expression. The present study was designed to investigate whether B-Myb deletion in colorectal cancer could potentiate the immune efficacy of BTZ against colorectal cancer and to clarify the underlying mechanism. Stable B-Myb knockdown was induced in colorectal cancer cells, which increased apoptosis of the cancer cells relative to the control group in vitro and in vivo. We found that BTZ exhibited more favourable efficacy in B-Myb-defective colorectal cancer cells and tumor-bearing mice. BTZ treatment led to differential expression of genes enriched in the p53 signaling pathway promoted more powerful downstream DNA damage, and arrested cell cycle in B-Myb-defective colorectal cancer. In contrast, recovery of B-Myb in B-Myb-defective colorectal cancer cells abated BTZ-related DNA damage, cell cycle arrest, and anticancer efficacy. Moreover, BTZ promoted DNA damage-associated enhancement of immunogenicity, as indicated by potentiated expression of HMGB1 and HSP90 in B-Myb-defective cells, thereby driving M1 polarization of macrophages. Collectively, B-Myb deletion in colorectal cancer facilitates the immunogenic death of cancer cells, thereby further promoting the immune efficacy of BTZ by amplifying DNA damage. The present work provides an effective molecular target for colorectal cancer immunotherapy with BTZ.
Real-time efficient sensing of machine-soil interactions, especially precise tire-ground contact information, plays a critical role in cultivation, seeding, and harvesting for smart agriculture. ...However, the complicated agricultural environment poses a considerable challenge to traditional rigid sensors, which cannot suffer from both large deformation and electromagnetic interference. Here, we report a novel soft-metal BiInSn bonding-enabled recyclable and anti-interference flexible multilayer piezoelectric sensor for monitoring tractor tire strain. The printed BiInSn-ink electrode fully wraps the surface fibers of porous BaTiO3/PVDF-HFP electrospun films only through a low pressure at low temperature due to its unique thermal-softening effects, which of the adhesion strength is superior to the intrinsic tension limit of the film. The compact multilayer piezoelectric sensor is thus easily prepared, remarkably increasing the output voltage compared to a single-layer case (up to 300% for three layers). Benefiting from the low melting point of the BiInSn alloy, the sensors are easily recyclable compared to conventional metal electrodes prepared with copper, silver, and gold. In addition, its high electrical conductivity also enables the shielding layer to achieve ultrahigh shielding effectiveness of 2100 dB mm−1. This sensor can be demonstrated for tire strain sensing under complex operating conditions such as plowing, harrowing, and fertilizer application. These findings serve as a foundation for accelerating the development of smart agriculture.
Display omitted
•Soft-metal bonded piezoelectric multilayer configuration exhibits recyclable and interference-resistant performance.•The output voltage of the three-layer piezoelectric sensor is increased by 300% compared to a single layer.•The multilayer piezoelectric sensor can achieve ultrahigh shielding effectiveness of 2100 dB mm−1.•The multilayer piezoelectric sensor successfully monitored tractor tire strain operating in a complex agricultural environment.
The relationship between plate tectonics and the reworking of continental crust remains controversial. Multistage, hornblende-free, S-type granites across the Malay Peninsula Sn belt are ideal for ...investigating this research question. Here we present zircon U-Pb ages, in-situ apatite Nd and zircon Hf isotope data, and whole-rock major and trace element data for these S-type granites and spatially associated dykes. Four generations of Permian–Triassic (276–272, 262–260, 231–222, and 202 Ma) S-type granites were identified. The different S-type granites show distinct in-situ zircon Hf and apatite Nd isotopic compositions, implying generation from different sedimentary protoliths. Input of mantle-derived components for the formation of all these S-type granites, further indicating that both continental crustal reworking and growth occurred in the Malay Peninsula during the Permian–Triassic. A 250 Ma dolerite dyke in the Eastern Province was derived from an E-MORB-like mantle source. However, a 202 Ma monzonite dyke in the Western Province, was derived from mafic magmas produced by the melting of enriched mantle, followed by subsequent incorporation of crustal materials. All these S-type granitic magmas were reduced that inherited from sedimentary protoliths, which were favourable for Sn mineralization. Apatite F-Cl concentrations and F/Cl ratios in the S-type granites and related dykes changed systematically through time. We infer that the formation of these S-type granites and related dykes corresponds to the Palaeo-Tethyan evolution (i.e., early subduction of Palaeo-Tethyan oceanic lithosphere and subsequent collision between the Sibumasu and Indochina blocks). Our study also support that multistage S-type granites can be generated in distinct tectonic environments at different times in the same region.
Display omitted
•Four episodes of S-type granites (276–202 Ma) in Malay Peninsula were identified.•S-type granitic magmas in Malay Peninsula are favourable for tin mineralization.•The generation of multistage S-type granites was a response to Tethyan evolution.
•The present work demonstrates the original innovations with the following details: 1). MYBL2 (B-Myb) absence in colorectal cancer contributes to photodynamic therapy (PDT) resistance. 2). MYBL2 ...deletion in colorectal cancer could activate NF-κB to up-regulate ABCG2 and thus efflux photosensitizers, leading to reduced efficacy of Ce6-PDT thereupon.
Photodynamic therapy (PDT) may be an effective therapeutic strategy for colorectal cancer at an early stage. However, malignant cells’ resistance to photodynamic agents can lead to treatment failure. MYBL2 (B-Myb) is an oncogene in colorectal carcinogenesis and development, for which little research has focused on its effect on drug resistance.
In the present work, a colorectal cancer cell line with a stable knockdown of MYBL2 (ShB-Myb) was constructed first. Chlorin e6 (Ce6) was utilized to induced PDT. The anti-cancer efficacy was measured by CCK-8, PI staining, and Western blots. The drug uptake of Ce6 was assayed by flow cytometry and confocal microscopy. The ROS generation was detected by the CellROX probe. DDSB and DNA damage were assayed through comet experiment and Western blots. The over-expression of MYBL2 was conducted by MYBL2 plasmid.
The findings indicated that the viability of ShB-Myb treated with Ce6-PDT was not decreased compared to control SW480 cells (ShNC), which were resistant to PDT. Further investigation revealed reduced photosensitizer enrichment and mitigated oxidative DNA damage in colorectal cancer cells with depressed MYBL2. It turned out that SW480 cells knocking down MYBL2 showed phosphorylation of NF-κB and led to up-regulation of ABCG2 expression thereupon. When MYBL2 was replenished back in MYBL2-deficient colorectal cancer cells, phosphorylation of NF-κB was blocked and ABCG2 expression up-regulation was suppressed. Additionally, replenishment of MYBL2 also increased the enrichment of Ce6 and the efficacy of PDT.
In summary, MYBL2 absence in colorectal cancer contributes to drug resistance by activating NF-κB to up-regulate ABCG2 and thereby leading to photosensitizer Ce6 efflux. This study provides a novel theoretical basis and strategy for how to effectively improve the anti-tumor efficacy of PDT.
Display omitted
Aims:
This study aimed to investigate the association between the use of sodium-glucose transporter 2 inhibitors (SGLT-2i) and the risk of diabetic ketoacidosis (DKA), lower limb amputation (LLA), ...urinary tract infections (UTI), genital tract infections (GTI), bone fracture, and hypoglycemia in cohort studies.
Methods:
A systematic search was conducted in the PubMed and Embase databases to identify cohort studies comparing the safety of SGLT-2i versus other glucose-lowering drugs (oGLD) in patients with type 2 diabetes mellitus (T2DM). The quality of the studies was assessed using the Newcastle-Ottawa Scale. Primary endpoints were DKA and LLA, while secondary endpoints included UTI, GTI, bone fracture, and hypoglycemia. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated.
Results:
A total of 9,911,454 patients from 40 cohort studies were included in the analysis. SGLT-2i use was associated with a higher risk of DKA (HR: 1.21, 95% CI: 1.07–1.38,
p
= 0.003) and GTI (HR: 2.72, 95% CI: 2.48–2.98,
p
< 0.01). However, it was not associated with an increased risk of LLA (HR: 1.06, 95% CI: 0.92–1.23,
p
= 0.42), UTI (HR: 0.99, 95% CI: 0.89–1.10,
p
= 0.83), or bone fracture (HR: 0.99, 95% CI: 0.94–1.04,
p
= 0.66). Furthermore, SGLT-2i was associated with a reduced risk of hypoglycemia. Furthermore, compared to dipeptidyl peptidase 4 inhibitors, SGLT-2i as a class and individually was associated with an increased risk of DKA. Canagliflozin specifically increased the risk of LLA (HR: 1.19, 95% CI: 1.04–1.36,
p
= 0.01). The subgroup analysis suggested that SGLT-2i increased the risk of LLA among patients with a history of cardiovascular disease.
Conclusion:
SGLT-2i versus oGLD was associated with a similar occurrence of LLA, UTI, and bone fracture. However, SGLT-2i was associated with a higher risk of DKA and GTI than oGLD. These findings provide valuable information on the safety profile of SGLT-2i in patients with T2DM and can help inform clinical decision-making.
Hepatitis E, an acute zoonotic disease caused by the hepatitis E virus (HEV), has a relatively high burden in developing countries. The current research model on hepatitis E mainly uses experimental ...animal models (such as pigs, chickens, and rabbits) to explain the transmission of HEV. Few studies have developed a multi-host and multi-route transmission dynamic model (MHMRTDM) to explore the transmission feature of HEV. Hence, this study aimed to explore its transmission and evaluate the effectiveness of intervention using the dataset of Jiangsu Province.
We developed a dataset comprising all reported HEV cases in Jiangsu Province from 2005 to 2018. The MHMRTDM was developed according to the natural history of HEV cases among humans and pigs and the multi-transmission routes such as person-to-person, pig-to-person, and environment-to-person. We estimated the key parameter of the transmission using the principle of least root mean square to fit the curve of the MHMRTDM to the reported data. We developed models with single or combined countermeasures to assess the effectiveness of interventions, which include vaccination, shortening the infectious period, and cutting transmission routes. The indicator, total attack rate (TAR), was adopted to assess the effectiveness.
From 2005 to 2018, 44 923 hepatitis E cases were reported in Jiangsu Province. The model fits the data well (R
= 0.655, P < 0.001). The incidence of the disease in Jiangsu Province and its cities peaks are around March; however, transmissibility of the disease peaks in December and January. The model showed that the most effective intervention was interrupting the pig-to-person route during the incidence trough of September, thereby reducing the TAR by 98.11%, followed by vaccination (reducing the TAR by 76.25% when the vaccination coefficient is 100%) and shortening the infectious period (reducing the TAR by 50.05% when the infectious period is shortened to 15 days).
HEV could be controlled by interrupting the pig-to-person route, shortening the infectious period, and vaccination. Among these interventions, the most effective was interrupting the pig-to-person route.
Low silicon rice gene 1 (
Lsi1
) belongs to a member of
Nod26
-like major intrinsic protein (
NIP
) subfamily and is thought to control silicon (Si) accumulation in rice. In order to further ...elucidate its regulatory mechanisms in the defense of rice plants to enhanced ultraviolet-B (UV-B) radiation stress,
Lsi1
was subjected to suppressed and overexpressed treatments in a UV-B tolerance rice accession Lemont as well as to overexpressed treatment in a UV-B sensitive rice accession Dular. The results showed that transcript levels of
Lsi1
increased in
Lsi1
-overexpressed transgenic lines of rice accessions Lemont and Dular, but down-regulated in
Lsi1
-RNAi transgenic line of Lemont in comparison with their wild types (WT). A similar tendency was found in the root Si uptake and the Si concentrations in leaves. Further, the different transgenic rice lines and their WT were exposed to enhance UV-B radiation, study by suppression subtractive hybridization (SSH) found that
Lsi1
not only could regulate the expression of phenylalanine ammonia-lyase (
PAL
), 4-coumarate-CoA ligase (
4CL
) and photolyase (
PL
), but also could induce other signal transduction-, detoxification-, resistance-, and photosynthesis-related genes. The findings suggested that the regulation of silicon nutrient by enhancing/inhibiting expression of
Lsi1
could effectively induce the transcription of the mRNAs relative to tolerance in rice.
PDF
