To develop and validate a radiomics model for evaluating pathologic complete response (pCR) to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer (LARC).
We enrolled 222 ...patients (152 in the primary cohort and 70 in the validation cohort) with clinicopathologically confirmed LARC who received chemoradiotherapy before surgery. All patients underwent T2-weighted and diffusion-weighted imaging before and after chemoradiotherapy; 2,252 radiomic features were extracted from each patient before and after treatment imaging. The two-sample
test and the least absolute shrinkage and selection operator regression were used for feature selection, whereupon a radiomics signature was built with support vector machines. Multivariable logistic regression analysis was then used to develop a radiomics model incorporating the radiomics signature and independent clinicopathologic risk factors. The performance of the radiomics model was assessed by its calibration, discrimination, and clinical usefulness with independent validation.
The radiomics signature comprised 30 selected features and showed good discrimination performance in both the primary and validation cohorts. The individualized radiomics model, which incorporated the radiomics signature and tumor length, also showed good discrimination, with an area under the receiver operating characteristic curve of 0.9756 (95% confidence interval, 0.9185-0.9711) in the validation cohort, and good calibration. Decision curve analysis confirmed the clinical utility of the radiomics model.
Using pre- and posttreatment MRI data, we developed a radiomics model with excellent performance for individualized, noninvasive prediction of pCR. This model may be used to identify LARC patients who can omit surgery after chemoradiotherapy.
.
1D organic micro/nanostructures (OMNSs) based on π‐conjugated molecules are considered to be suitable candidates as photonic units due to their unique photophysical advantages over traditional ones ...in low‐temperature solution‐processed approach, tunable emission color, the built‐in cavity for optical confinement, and so forth. These inherent characteristics of OMNSs make them have broad application prospects in photonics devices, such as nanolasers, optical waveguides, and optical logical gates. In this review, the recent processes of OMNSs in terms of light generation, light confinement, and propagation are introduced, separately. Some representative works of OMNSs are discussed in the direction of optical modulation and processing. However, huge challenges still remain before the OMNSs are actually used as components of optical circuits in the photonics chips. The summary and the expectations are presented for the future development of 1D organic micro/nanostructures photonics.
1D organic micro/nanostructures have great potential in nanoscale integrated optical circuits as photonic components due to their intrinsic capabilities to generate and confine optical signals efficiently. Herein, the recent advances of 1D micro/nanostructures in photonic applications are reviewed. Then, the prospects and suggestions for future development are presented.
Bile acids are synthesized in the liver and are the major component in bile. Impaired bile flow leads to cholestasis that is characterized by elevated levels of bile acid in the liver and serum, ...followed by hepatocyte and biliary injury. Although the causes of cholestasis have been extensively studied, the molecular mechanisms as to how bile acids initiate liver injury remain controversial. In this chapter, we summarize recent advances in the pathogenesis of bile acid induced liver injury. These include bile acid signaling pathways in hepatocytes as well as the response of cholangiocytes and innate immune cells in the liver in both patients with cholestasis and cholestatic animal models. We focus on how bile acids trigger the production of molecular mediators of neutrophil recruitment and the role of the inflammatory response in this pathological process. These advances point to a number of novel targets where drugs might be judged to be effective therapies for cholestatic liver injury.
Objective
To quantitatively compare the diagnostic values of various diffusion parameters obtained from mono- and biexponential diffusion-weighted imaging (DWI) models and diffusion kurtosis imaging ...(DKI) in differentiating between benign and malignant solitary pulmonary lesions (SPLs).
Methods
Multiple b-value DWIs and DKIs were performed in 89 patients with SPL by using a 3-T magnetic resonance (MR) imaging unit. The apparent diffusion coefficient (ADC) of various b-value sets, true diffusivity (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), apparent diffusional kurtosis (K
app
), and kurtosis-corrected diffusion coefficient (D
app
) were calculated and compared between the malignant and benign groups using a Mann-Whitney U test. Receiver-operating characteristic analysis was performed for all parameters.
Result
The ADC
(0, 150)
values of malignant tumors were lower than those of the benign group (
p
= 0.01). The ADC
(0, 300)
, ADC
(0, 500)
, ADC
(0, 600),
ADC
(0, 800)
, ADC
(0, 1000),
ADC
total
, D, and D
app
of malignant tumors were significantly lower than those of benign lesions (all
p
< 0.001). D*, f, and K
app
showed no statistically significant differences between the two groups. ADC
total
showed the highest area under the curve (AUC = 0.862), followed by ADC
(0, 800)
(AUC = 0.844), ADC
(0, 600)
(AUC = 0.843), D(AUC = 0.834), ADC
(0, 1000)
(AUC = 0.834) and ADC
(0, 500)
(AUC = 0.824), D
app
(AUC = 0.796), and ADC
(0, 300)
(AUC = 0.773). However, the difference in diagnostic efficacy among these parameters was not statistically significant (
p
> 0.05).
Conclusion
Intravoxel incoherent motion (IVIM) and DKI-derived parameters have similar performance compared with conventional ADC in differentiating SPLs.
Key Points
• Mono- and biexponential DWI and DKI are feasible for differentiating SPLs.
• ADC
(0, ≥500)
has better performance than ADC
(0, <500)
in assessing SPLs.
• IVIM and DKI have similar performance compared with conventional DWI in differentiating SPLs.
Peroxisomes account for ~35% of total H2O2 generation in mammalian tissues. Peroxisomal ACOX1 (acyl‐CoA oxidase 1) is the first and rate‐limiting enzyme in fatty acid β‐oxidation and a major producer ...of H2O2. ACOX1 dysfunction is linked to peroxisomal disorders and hepatocarcinogenesis. Here, we show that the deacetylase sirtuin 5 (SIRT5) is present in peroxisomes and that ACOX1 is a physiological substrate of SIRT5. Mechanistically, SIRT5‐mediated desuccinylation inhibits ACOX1 activity by suppressing its active dimer formation in both cultured cells and mouse livers. Deletion of SIRT5 increases H2O2 production and oxidative DNA damage, which can be alleviated by ACOX1 knockdown. We show that SIRT5 downregulation is associated with increased succinylation and activity of ACOX1 and oxidative DNA damage response in hepatocellular carcinoma (HCC). Our study reveals a novel role of SIRT5 in inhibiting peroxisome‐induced oxidative stress, in liver protection, and in suppressing HCC development.
Synopsis
This study reveals a role for SIRT5 in regulating peroxisomal H2O2 and ROS homeostasis and indicates its potential function in liver protection and hepatocellular carcinoma suppression.
SIRT5 is localized in peroxisomes where it controls H2O2 metabolism.
SIRT5‐mediated desuccinylation inhibits ACOX1 activity by suppressing its active dimer formation.
SIRT5 downregulation increases ACOX1 activity and oxidative DNA damage response in HCC.
This study reveals a role for SIRT5 in regulating peroxisomal H2O2 and ROS homeostasis and indicates its potential function in liver protection and hepatocellular carcinoma suppression.
Tumor cells adapt to excessive oxidative stress by actuating reactive oxygen species (ROS)‐defensing system, leading to a resistance to oxidation therapy. In this work, self‐delivery photodynamic ...synergists (designated as PhotoSyn) are developed for oxidative damage amplified tumor therapy. Specifically, PhotoSyn are fabricated by the self‐assembly of chlorine e6 (Ce6) and TH588 through π–π stacking and hydrophobic interactions. Without additional carriers, nanoscale PhotoSyn possess an extremely high drug loading rate (up to 100%) and they are found to be fairly stable in aqueous phase with a uniform size distribution. Intravenously injected PhotoSyn prefer to accumulate at tumor sites for effective cellular uptake. More importantly, TH588‐mediated MTH1 inhibition could destroy the ROS‐defensing system of tumor cells by preventing the elimination of 8‐oxo‐2′‐deoxyguanosine triphosphate (8‐oxo‐dG), thereby exacerbating the oxidative DNA damage induced by the photodynamic therapy (PDT) of Ce6 under light irradiation. As a consequence, PhotoSyn exhibit enhanced photo toxicity and a significant antitumor effect. This amplified oxidative damage strategy improves the PDT efficiency with a reduced side effect by increasing the lethality of ROS without generating superabundant ROS, which would provide a new insight for developing self‐delivery nanoplatforms in photodynamic tumor therapy in clinic.
Carrier free photodynamic synergists are developed for oxidative damage amplified tumor therapy by destroying the reactive oxygen species (ROS)‐defensing system without generating excessive ROS, which shed light on the development of self‐delivery nanoplatforms for efficient photodynamic therapy by utilizing the limited oxygen in hypoxic tumors.
The rapid development of information technology has resulted in a growing demand for low‐dimensional photonic materials. Organic semiconductor materials play an important role in various photonic ...devices due to their adjustable physicochemical properties, while individual organic crystals do not exhibit the desired performance due to the limitations of their simple structure. Branched organic crystals with inherent multichannel characteristics based on π‐conjugated molecules are favorable components in optoelectronics. However, the preparation of branched organic crystals still faces great challenges before they can be applied in integrated optoelectronic devices. In this Review, the development and representative examples of branched organic crystals in terms of molecular design, synthesis, and advanced applications are discussed. We also provide a summary and outlook for the direction of future research on branched organic crystals as excellent candidates in photonic integrated circuits.
Low‐dimensional hierarchical organic crystals with branched architectures are suitable fundamental building blocks in integrated photonic devices because of their inherent multichannel characteristics for the efficient generation and processing of optical signals. This Review summarizes recent advances in the synthesis and photonic applications of organic branched crystals as well as the challenges and prospects for their future development.
We report a ratiometric fluorescent sensor based on monochlorinated BODIPY for highly selective detection of glutathione (GSH) over cysteine (Cys)/homocysteine (Hcy). The chlorine of the ...monochlorinated BODIPY can be rapidly replaced by thiolates of biothiols through thiol–halogen nucleophilic substitution. The amino groups of Cys/Hcy but not GSH further replace the thiolate to form amino-substituted BODIPY. The significantly different photophysical properties of sulfur- and amino-substituted BODIPY enable the discrimination of GSH over Cys and Hcy. The sensor was applied for detection of GSH in living cells.
Conventional oxygen‐dependent photodynamic therapy (PDT) has faced severe challenges because of the non‐specificity of most available photosensitizers (PSs) and the hypoxic nature of tumor tissues. ...Here, an O2 self‐sufficient cell‐like biomimetic nanoplatform (CAT‐PS‐ZIF@Mem) consisting of the cancer cell membrane (Mem) and a cytoskeleton‐like porous zeolitic imidazolate framework (ZIF‐8) with the embedded catalase (CAT) protein molecules and Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4, defined as PS) is developed. Because of the immunological response and homologous targeting abilities of the cancer cell membrane, CAT‐PS‐ZIF@Mem is selectively accumulated at the tumor site and taken up effectively by tumor cells after intravenous injection. After the intracellular H2O2 penetration into the framework, it is catalyzed by CAT to produce O2 at the hypoxic tumor site, facilitating the generation of toxic 1O2 for highly effective PDT in vivo under near‐infrared irradiation. By integrating the immune escape, cell homologous recognition, and O2 self‐sufficiency, this cell‐like biomimetic nanoplatform demonstrates highly specific and efficient PDT against hypoxic tumor cells with much reduced side‐effect on normal tissues.
An O2 self‐sufficient cell‐like biomimetic nanoplatform based on zeolitic imidazolate framework (ZIF‐8) is developed for effective photodynamic therapy (PDT). In vitro and in vivo investigations confirm that this cell‐like PDT agent possesses immune escape, homologous targeting, and O2 self‐sufficient capabilities for highly specific PDT against hypoxic tumor cells.
Modulating tumor microenvironment to amplify the therapeutic efficiency would be a novel strategy for effective cancer treatment. In this work, based on the TPZ-loaded porphyrinic metal organic ...framework PCN-224 (PCN stands for porous coordination network), a cancer cell membrane-coated nanoplatform (TPZ@PCN@Mem) was fabricated for tumor targeted PDT and the successively resulting hypoxia-amplified bioreductive therapy. After administration, TPZ@PCN@Mem exhibited the selective accumulation and long-term retention at tumor tissue due to the immune escape and homologous targeting endowed by the cancer membrane coating. Upon light irradiation, PCN-224-mediated toxic reactive oxygen species (ROS) were generated for PDT, and the resulting local hypoxia microenvironment would further accelerate the activation of TPZ for enhanced chemotherapy in 4T1 orthotopic tumor. The cascade synergistic therapeutic effects of TPZ@PCN@Mem could significantly suppress the primary tumor growth, and also inhibit its distal metastasis with minimal side effects. The study indicated an overwhelming superiority of utilizing this bioinspired strategy for tumor targeted PDT and hypoxia-activated bioreductive therapy, which provided a new insight for precise and effective tumor treatment.
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