Focal therapy (FT) has been gaining popularity as a treatment option for localized intermediate-risk prostate cancer (PCa) due to the associated lower morbidity compared to whole-gland treatment. ...However, there is an increased risk of local cancer recurrence requiring subsequent treatment in a small proportion of patients.
To conduct a systematic review and meta-analysis to better describe and analyze patient postoperative, oncologic, and functional outcomes for those who underwent salvage radical prostatectomy (sRP) to manage their primary FT failure.
A systematic review was completed using three databases (PubMed, Embase, and CINAHL) from October to December 2021 to identify data on outcomes in patients who received sRP for cancer recurrence after prior focal treatment.
12 articles (482 patients) were included. Median time to sRP was 24 months. Median follow-up time was 27 months. A meta-analysis revealed a postoperative complication rate of 15% (95% CI: 0.09, 0.24), with 4.6% meeting criteria for a major complication Clavien (CG) grade ≥3. Severe GU toxicity was seen in 3.6% of the patients, and no patients had severe GI toxicity. Positive surgical margins (PSM) were found in 27% (95% CI: 0.19, 0.37). Biochemical recurrence (BCR) after sRP occurred in 23% (95% CI: 0.17, 0.30), indicating a BCR-free probability of 77% at 2 years. Continence (pad-free) and potency (ability to have penetrative sex) were maintained in 67% (95% CI: 0.53, 0.78) and 37% (95% CI: 0.18, 0.62) at 12 months, respectively.
Our evidence shows acceptable complication rates and oncologic outcomes; however, with suboptimal functional outcomes for patients undergoing sRP for recurrent PCa after prior FT. Inferior outcomes were observed for salvage treatment compared to primary radical prostatectomy (pRP). More high-quality studies are needed to better characterize outcomes after this sequence of PCa treatments.
We looked at treatment outcomes and toxicity for men treated with sRP for prior FT failure. We conclude that these patients will have significant detriment to genitourinary function, with outcomes being worse than those for pRP patients.
The bacterial species,
, is associated with several gastrointestinal diseases, and poses serious health threats owing to its resistance to antibiotics.
spp., on the other hand, possess probiotic ...activities that have beneficial effects in humans. However, the mechanisms by which
spp. harbor favorable functions and act against
infection remain to be explored. The aim of this study was to investigate the ability of bacterial strains,
and
, termed GMNL-74 and GMNL-185, respectively, to inhibit
growth and inflammation. Our results showed that GMNL-74 and GMNL-185 possess potent antimicrobial activity against multidrug resistant (MDR)-
. In addition, an in vitro cell-based model revealed that the inhibition of
adhesion and invasion of gastric epithelial cells and interleukin-8 production were significantly decreased by treatment with both the
strains. In vivo studies demonstrated that colonization of
and induced inflammation in the mouse stomach were also alleviated by these
strains. Furthermore, the abundance of beneficial gut bacteria, including
spp. and
, were significantly increased in
-infected mice treated with GMNL-74 and GMNL-185. These results demonstrate that
spp. ameliorate
-induced inflammation and supports beneficial gut specific bacteria that act against
infection.
This study aimed at developing and validating a scoring model to stratify critically ill patients after cardiac surgery based on risk for dysphagia, a common but often neglected complication.
Data ...were prospectively collected and analyzed from January 2016 to June 2017 from 395 consecutive post cardiac surgery patients at the cardiac care unit (CCU) at a single center; 103 (26.1%) developed dysphagia. Univariate and multivariate logistic analyses were used to identify independent predictors for dysphagia. The survival nomogram was developed on the basis of a multivariable Cox model, which allowed us to obtain survival probability estimations. The predictive performance of the nomogram was verified for discrimination and calibration. Areas under receiver operating characteristic curve analysis were used to illustrate and evaluate the diagnostic performance of the novel model.
The final novel scoring model, named SSG-OD, consists of three independent factors: gastric intubation (OR = 1.024, 95% CI 1.015-1.033), sedative drug use duration (OR = 1.031, 95% CI 1.001-1.063) and stroke or not (OR = 6.182, 95% CI 3.028-12.617). SSG-OD identified patients at risk for dysphagia with sensitivity of 68.5% and specificity of 89.0% (OR = 0.833, 95% CI: 0.782-0.884). The positive and negative likelihood ratios were 6.22 and 0.35.
The novel SSG-OD scoring system to risk stratify CCU patients for dysphagia is an easy-to-use bedside prognostication aid with good predictive performance and the potential to reduce aspiration incidence and accelerate recovery.
Three red cyclometalated iridium(iii) complexes (4tfmpq)
Ir(dipdtc), (4tfmpq)
Ir(dpdtc) and (4tfmpq)
Ir(Czdtc) (4tfmpq = 4-(4-(trifluoromethyl)phenyl)quinazoline, dipdtc =
,
-diisopropyl ...dithiocarbamate, dpdtc =
,
-diphenyl dithiocarbamate, and Czdtc =
-carbazolyl dithiocarbamate) containing the unique four-membered Ir-S-C-S backbone ring were synthesized in five minutes at room temperature with good yields, and the Gibbs free energy calculation results indicate that all reactions are exothermic and thermodynamically favorable processes. The emission colors (
= 641-611 nm), photoluminescence quantum efficiencies (
= 58.3-93.0%) and bipolar properties can be effectively regulated by introducing different electron-donating substituents into the dithiocarbamate ancillary ligands. Employing these emitters, organic light emitting diodes (OLEDs) with double emissive layers exhibit excellent performances with a maximum brightness over 60 000 cd m
, a maximum current efficiency of 40.68 cd A
, a maximum external quantum efficiency (EQE
) of 30.54%, and an EQE of 26.79% at the practical luminance of 1000 cd m
. These results demonstrate that Ir(iii) complexes with sulfur-containing ligands can be rapidly synthesized at room temperature, which is key to the production of metal luminescent materials for large-scale application in highly efficient OLEDs.
A novel series of 5‐substituted/unsubstituted 1,2,4triazolo3,4‐b1,3,4 thiadiazine compounds has been achieved successfully through chemoselective reduction of the C = N bond, based on our prior work. ...Initial biological evaluation illustrated that the most active derivative 7j exhibited significant cell growth inhibitory activity toward MCF‐7, A549, HCT116, and A2780 with the IC50 values of 0.75, 0.94, 2.90, and 4.15 μM, respectively. Most importantly, all the representative analogs did not demonstrate obvious cytotoxic activity against the non‐tumoural cell line HEK‐293 (IC50 > 100 μM). The mechanism study revealed that 7j caused the G2/M phase arrest, induced cell apoptosis in HeLa cells in a concentration‐dependent manner, and also showed potent tubulin polymerization inhibitory effect. Meanwhile, 7j exerted significant antivascular activity in the wound‐healing and tube formation assays. These observations indicate that 5‐unsubstituted 6,7‐dihydro‐5H‐1,2,4triazolo3,4‐b1,3,4thiadiazine scaffold might be considered as a potential lead for antitubulin inhibitors to develop highly efficient anticancer agents with potent selectivity over normal human cells.
Multifunctional electronics featuring optical transparency, portability, mechanical flexibility, light-weight and environment-friendly are of great demands for next-generation smart electronics. ...Memristor represents one of the important chains in next-generation devices as the information computing and storage component. Here, we design the transparent flexible structure based on van der Waals heteroepitaxial AZO/NiO/AZO/muscovite (ANA/muscovite) for a memristor application. The (ANA/muscovite) memristor satisfies all the hardest requirements of a transparent soft device such as optical transparency over 80% in visible light and high performance with a ON/OFF resistance ratio > 105, stable endurance to 103 cycles and long retention time of 105 s. In addition, the ANA/muscovite memristor can work at various bending radii down to 5 mm, a mechanical bending after 1000 cycles at a curvature with a radius of 6.5 mm and a high temperature up to 185 °C, which deliver a pathway for future applications in flexible transparent smart electronics.
Display omitted
•A transparent flexible memristor based on the van der Waals heteroepitaxial grwoth composed of Al-doped ZnO (AZO)/NiO/AZO (ANA) sandwich structure on the muscovite substrate was fabricated.•ANA/muscovite memristor exhibits not only transparent and flexible memristor with the ON/OFF resistance ratio >105, the stable endurance to 103 cycles and the long retention time of 105 s, but also the excellent electrical performances together with the mechanical flexibility, the durability and the thermal stability.•The ANA/muscovite memristor can work at various bending radii down to 5 mm, the mechanical bending after 1000 cycles at the bending radius of 6.5 mm and the high temperature up to 185 °C
Intercellular communications are important for maintaining normal physiological processes. An important intercellular communication is mediated by the exchange of membrane-enclosed extracellular ...vesicles. Among various vesicles, exosomes can be detected in a wide variety of biological systems, but the regulation and biological implication of exosome secretion/uptake remains largely unclear.
Cellular retinoic acid (RA) binding protein 1 (Crabp1) knockout (CKO) mice were used for in vivo studies. Extracellular exosomes were monitored in CKO mice and relevant cell cultures including embryonic stem cell (CJ7), macrophage (Raw 264.7) and hippocampal cell (HT22) using Western blot and flow cytometry. Receptor Interacting Protein 140 (RIP140) was depleted by Crispr/Cas9-mediated gene editing. Anti-inflammatory maker was analyzed using qRT-PCR. Clinical relevance was accessed by mining multiple clinical datasets.
This study uncovers Crabp1 as a negative regulator of exosome secretion from neurons. Specifically, RIP140, a pro-inflammatory regulator, can be transferred from neurons, via Crabp1-regulated exosome secretion, into macrophages to promote their inflammatory polarization. Consistently, CKO mice, defected in the negative control of exosome secretion, have significantly elevated RIP140-containing exosomes in their blood and cerebrospinal fluid, and exhibit an increased vulnerability to systemic inflammation. Clinical relevance of this pathway is supported by patients' data of multiple inflammatory diseases. Further, the action of Crabp1 in regulating exosome secretion involves its ligand and is mediated by its downstream target, the MAPK signaling pathway.
This study presents the first evidence for the regulation of exosome secretion, which mediates intercellular communication, by RA-Crabp1 signaling. This novel mechanism can contribute to the control of systemic inflammation by transferring an inflammatory regulator, RIP140, between cells. This represents a new mechanism of vitamin A action that can modulate the homeostasis of system-wide innate immunity without involving gene regulation. Video Abstract.
Let
F
be a local field of characteristic not 2. We propose a definition of stable conjugacy for all the covering groups of
Sp
(
2
n
,
F
)
constructed by Brylinski and Deligne, whose degree we denote ...by
m
. To support this notion, we follow Kaletha’s approach to construct genuine epipelagic
L
-packets for such covers in the non-archimedean case with
p
∤
2
m
, or some weaker variant when
4
∣
m
; we also prove the stability of packets when
F
⊃
Q
p
with
p
large. When
m
=
2
, the stable conjugacy reduces to that defined by J. Adams, and the epipelagic
L
-packets coincide with those obtained by
Θ
-correspondence. This fits within Weissman’s formalism of
L
-groups. For
n
=
1
and
m
even, it is also compatible with the transfer factors proposed by K. Hiraga and T. Ikeda.
Seven new compounds, including one dimer novel skeleton, chamaecyformosanin A (
); three diterpenes, chamaecyformosanins B-D (
-
); one sesquiterpene, chamaecyformosanin E (
); and two monoterpenes, ...chamaecyformosanins F and G (
and
) were isolated from the methanol extract of the bark of
var.
. Their structures were established by the mean of spectroscopic analysis and the comparison of NMR data with those of known analogues. Their structures were elucidated on the basis of physicochemical evidence, in-depth NMR spectroscopic analysis, and high-resolution mass spectrometry. Furthermore, the isolated compounds were subjected to an evaluation of their antimicrobial activity. Metabolites
,
, and
present antibacterial activities. It is worth mentioning that the chemical composition of the bark of
.
var.
has never been studied in the past. This is the first time the barks from
.
var.
were studied and two new skeleton compounds,
and
, were obtained.
High-risk human papillomavirus (HPV) 16-infected oral cavity squamous cell carcinoma (OCSCC) differs significantly from non-HPV-infected OCSCC. However, the molecular pathogenesis of HPV-infected ...OCSCC remains unclear. Paxillin (PXN) has been reported to promote lung tumor progression by miR-218 targeting. In addition, expression of miR-218 has been shown to be reduced by HPV16 E6 in cervical cancer. We thus asked whether PXN can promote tumor progression by E6-reduced miR-218 in OCSCC, especially in HPV-infected OCSCC. Mechanistic studies demonstrated that PXN expression increased markedly upon E6-mediated reductions in miR-218, resulting in increased colony formation and invasion capabilities in HPV-infected OCSCC cells. Among tumor specimens, HPV16/18 infection was negatively associated with miR-218 expression and positively associated with PXN expression. Kaplan-Meier and Cox regression models demonstrated that patients with low-miR-218 tumors or high-PXN tumors exhibited shorter overall survival (OS) and relapse-free survival (RFS) than those with high-miR-218 tumors or low-PXN tumors. Interestingly, HPV-infected patients with low-miR-218, high-PXN tumors and both combinations exhibited the worst OS and RFS compared with patients in their counterparts. These observations in patients were consistent with the findings from the cell model. Therefore, we suggest that PXN might be targeted to suppress tumor progression and consequently to improve outcomes in OCSCC, especially in HPV-infected OCSCC.
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