Tetramethylpyrazine Antagonizes the Subchronic Cadmium Exposure-Induced Oxidative Damage in Mouse Livers via the Nrf2/HO-1 Pathway.

Hepatic oxidative stress is an important mechanism of Cd-induced hepatotoxicity, and it is ameliorated by TMP. However, this underlying mechanism remains to be elucidated. To investigate the mechanism of the protective effect of TMP on liver injuries in mice induced by subchronic cadmium exposure, 60 healthy male ICR mice were randomly divided into five groups of 12 mice each, namely, control (CON), Cd (2 mg/kg of CdCl2), Cd + 100 mg/kg of TMP, Cd + 150 mg/kg of TMP, and Cd + 200 mg/kg of TMP, and were acclimatized and fed for 7 d. The five groups of mice were gavaged for 28 consecutive days with a maximum dose of 0.2 mL/10 g/day. Except for the control group, all groups were given fluoride (35 mg/kg) by an intraperitoneal injection on the last day of the experiment. The results of this study show that compared with the Cd group, TMP attenuated CdCl2-induced pathological changes in the liver and improved the ultrastructure of liver cells, and TMP significantly decreased the MDA level (p < 0.05) and increased the levels of T-AOC, T-SOD, and GSH (p < 0.05). The results of mRNA detection show that TMP significantly increased the levels of Nrf2 in the liver compared with the Cd group as well as the HO-1 and mRNA expression levels in the liver (p < 0.05). In conclusion, TMP could inhibit oxidative stress and attenuate Cd group-induced liver injuries by activating the Nrf2 pathway.

Combined effects of high-intensity ultrasound treatment and hydrogen peroxide addition on the thermal stabilities of myofibrillar protein emulsions at low ionic strengths.

In this study, the effects of high-intensity ultrasound (HIU) treatment combined with hydrogen peroxide (H2O2) addition on the thermal stability of myofibrillar protein (MP)-stabilized emulsions in low-salt conditions were investigated. Results showed that compared to using either HIU or H2O2 treatment alone, HIU treatment combined with H2O2 was most effective in enhancing the physical stability of emulsions. Moreover, the emulsion stabilized by MPs co-treated with HIU and H2O2 exhibited the most uniform distribution, highest absolute zeta potential, and optimal rheological properties upon heating. This combination effect during heating was caused by the inhibition of disulfide bond cross-linking of myosin heads by H2O2 and the dissociation of filamentous myosin structures using the HIU treatment. In addition, the results of oxidative stability analysis indicated that the addition of H2O2 increased the content of oxidation products; however, the overall influence on the oxidative stability of emulsions was not significant. In conclusion, the combination of HIU and H2O2 treatment is a promising approach to suppress heat-induced MP aggregation and improve the thermal stability of corresponding emulsions.

Association of peritumoral region features assessed on breast MRI and prognosis of breast cancer: a systematic review and meta-analysis.

BACKGROUND: Increasing attention has been given to the peritumoral region. However, conflicting findings have been reported regarding the relationship between peritumoral region features on MRI and the prognosis of breast cancer. PURPOSE: To evaluate the relationship between peritumoral region features on MRI and prognosis of breast cancer. MATERIALS AND METHODS: A retrospective meta-analysis of observational studies comparing either qualitative or quantitative assessments of peritumoral MRI features on breast cancer with poor prognosis and control subjects was performed for studies published till October 2022. Pooled odds ratios (ORs) or standardized mean differences and 95% confidence intervals (CIs) were estimated by using random-effects models. The heterogeneity across the studies was measured using the statistic I2. Sensitivity analyses were conducted to test this association according to different study characteristics. RESULTS: Twenty-four studies comprising 1853 breast cancers of poor prognosis and 2590 control participants were included in the analysis. Peritumoral edema was associated with non-luminal breast cancers (OR=3.56; 95%CI: 2.17, 5.83; p=.000), high expression of the Ki-67 index (OR=3.70; 95%CI: 2.41, 5.70; p =.000), high histological grade (OR=5.85; 95%CI: 3.89, 8.80; p=.000), lymph node metastasis (OR=2.83; 95%CI: 1.71, 4.67; p=.000), negative expression of HR (OR=3.15; 95%CI: 2.03, 4.88; p=.000), and lymphovascular invasion (OR=1.72; 95%CI: 1.28, 2.30; p=.000). The adjacent vessel sign was associated with greater odds of breast cancer with poor prognosis (OR=2.02; 95%CI: 1.68, 2.44; p=.000). Additionally, breast cancers with poor prognosis had higher peritumor-tumor ADC ratio (SMD=0.67; 95%CI: 0.54, 0.79; p=.000) and peritumoral ADCmean (SMD=0.29; 95%CI: 0.15, 0.42; p=.000). A peritumoral region of 2-20 mm away from the margin of the tumor is recommended. CONCLUSION: The presence of peritumoral edema and adjacent vessel signs, higher peritumor-tumor ADC ratio, and peritumoral ADCmean were significantly correlated with poor prognosis of breast cancer. CLINICAL RELEVANCE STATEMENT: MRI features of the peritumoral region can be used as a non-invasive index for the prognostic evaluation of invasive breast cancer. KEY POINTS: • Peritumoral edema was positively associated with non-luminal breast cancer, high expression of the Ki-67 index, high histological grade, lymph node metastasis, negative expression of HR, and lymphovascular invasion. • The adjacent vessel sign was associated with greater odds of breast cancers with poor prognosis. • Breast cancers with poor prognosis had higher peritumor-tumor ADC ratio and peritumoral ADCmean.

Interaction of the extracellular protease from Staphylococcus xylosus with meat proteins elucidated via spectroscopic and molecular docking.

This study aimed to assess the effect of an external protease secreted by Staphylococcus (S.) xylosus on the hydrolysis and flavor properties of meat protein. The results indicated that the protease significantly increased the solubility of myofibrillar proteins (MPs) and sarcoplasmic proteins (SPs) in water (P < 0.05), and altered their surface hydrophobicity and secondary structure. The results of micromorphological and free amino acids analyses suggested that the protease degraded the large and insoluble meat protein aggregates into small molecular proteins with uniform distribution and amino acids, especially glycine, glutamic acid, leucine, and cysteine. Moreover, the protease-catalyzed hydrolysis promoted the formation of some volatile compounds in the MPs and SPs. Additionally, molecular docking analysis suggested that hydrogen bond and hydrophobic interaction promoted the formation of a S. xylosus protease/meat protein complex. These results provided a basis for the future application of S. xylosus protease in meat products.

Selective recovery of lithium from spent lithium iron phosphate batteries.

The recovery of lithium from spent lithium iron phosphate (LiFePO4) batteries is of great significance to prevent resource depletion and environmental pollution. In this study, through active ingredient separation, selective leaching and stepwise chemical precipitation develop a new method for the selective recovery of lithium from spent LiFePO4 batteries by using sodium persulphate (Na2S2O8) to oxidize LiFePO4 to FePO4. The impact of various variables on the efficiency of lithium leaching was investigated. Moreover, a combination of thermodynamic analysis and characterization techniques such as X-ray diffraction and X-ray photoelectron spectroscopy was employed to elucidate the leaching mechanism. It was found that 98.65% of lithium could be selectively leached in just 35 minutes at 60°C with only 0.2 times excess of Na2S2O8. This high leaching efficiency can be attributed to the stability and lack of structural damage during the oxidation leaching process. The proposed process is economically viable and environmentally friendly, thus showing great potential for the large-scale recycling of spent LiFePO4 batteries.

Synergistic ultrasound pulsed electric field extraction of litchi peel polyphenols and determination of their properties.

The effects of pulsed electric field combined with ultrasound (PEF-US) on the recovery of polyphenols from litchi peels were investigated. In addition, the optimal purification parameters for polyphenol extracts and their biological activities were also explored in this study. Single-factor and orthogonal experiments were used to optimize the extraction conditions of polyphenols. After optimization, the total phenol content (TPC) of the sample extracted by PEF-US was 2.30 times higher than that of the sample extracted by traditional hot-water extraction. The mechanism of PEF-US enhancing polyphenol recovery was also revealed by morphological analysis of the powder surface. LX-7 was the best resin by comparing the purification effect of nine macroporous resins. The optimum conditions for purification of litchi peel polyphenols by LX-7 resin were also optimized through adsorption and desorption experiments. UHPLC-MS and HPLC results revealed that gentisic acid, catechin, procyanidin A2 and procyanidin B1 are four main substances in purified samples. The results of bioactivity experiments showed that the purified polyphenol samples had strong antioxidant and antibacterial activity. Overall, PEF-US is an efficient method for recovering polyphenols from litchi peels. Our study also provides a strategy for the comprehensive utilization of fruit processing waste.

The role of tumor-associated macrophages in hepatocellular carcinoma progression: A narrative review.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world, with complex etiology and mechanism, and a high mortality rate. Tumor-associated macrophages (TAMs) are an important part of the HCC tumor microenvironment. Studies in recent years have shown that TAMs are involved in multiple stages of HCC and are related to treatment and prognosis in HCC. The specific mechanisms between TAMs and HCC are gradually being revealed. This paper reviews recent advances in the mechanisms associated with TAMs in HCC, concentrating on an overview of effects of TAMs on drug resistance in HCC and the signaling pathways linked with HCC, providing clues for the treatment and prognosis determination of HCC.

A novel telomere-related genes model for predicting prognosis and treatment responsiveness in diffuse large B-cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) is a highly heterogeneous disease with diverse clinical and molecular features. Telomere maintenance is widely present in tumors, but there is a lack of relevant reports on the role of telomere-related genes (TRGs) in DLBCL. In this study, we used consensus clustering based on TRGs expression to identify two molecular clusters with distinct prognoses and immune cell infiltration. We developed a TRGs scoring model using univariate Cox regression and LASSO regression in the GSE10846 training cohort. DLBCL patients in the high-risk group had a worse prognosis than those in the low-risk group, as revealed by Kaplan-Meier curves. The scoring model was validated in the GSE10846 testing cohort and GSE87371 cohort, respectively. The high-risk group was characterized by elevated infiltration of activated DCs, CD56 dim natural killer cells, myeloid-derived suppressor cells, monocytes, and plasmacytoid DCs, along with reduced infiltration of activated CD4 T cells, Type 2 T helper cells, γδ T cells, NK cells, and neutrophils. Overexpression of immune checkpoints, such as PDCD1, CD274, and LAG3, was observed in the high-risk group. Furthermore, high-risk DLBCL patients exhibited increased sensitivity to bortezomib, rapamycin, AZD6244, and BMS.536924, while low-risk DLBCL patients showed sensitivity to cisplatin and ABT.263. Using RT-qPCR, we found that three protective model genes, namely TCEAL7, EPHA4, and ELOVL4, were down-regulated in DLBCL tissues compared with control tissues. In conclusion, our novel TRGs-based model has great predictive value for the prognosis of DLBCL patients and provides a promising direction for treatment optimization.

CHSY1 promotes CD8+ T cell exhaustion through activation of succinate metabolism pathway leading to colorectal cancer liver metastasis based on CRISPR/Cas9 screening.

BACKGROUND: The most common site of metastasis in colorectal cancer (CRC) is the liver and liver metastases occur in more than 50% of patients during diagnosis or treatment. The occurrence of metastasis depends on a series of events known as the invasive-metastasis cascade. Currently, the underlying genes and pathways regulating metastasis initiation in the liver microenvironment are unknown. METHODS: We performed systematic CRISPR/Cas9 screening using an in vivo mouse model of CRC liver metastasis to identify key regulators of CRC metastasis. We present the full results of this screen,which included a list of genes that promote or repress CRC liver colonization. By silencing these genes individually, we found that chondroitin sulfate synthase 1 (CHSY1) may be involved in CRC metastasis. We verified the function of CHSY1 and its involvement in liver metastasis of CRC through in vivo and in vitro experiments. RESULT: The results of TCGA and CRISPR/Cas9 showed that CHSY1 was overexpressed in CRC primary and liver metastasis tissues and indicated a worse clinical prognosis. In vitro and in vivo experiments confirmed that CHSY1 facilitated the liver metastasis of CRC and CHSY1 induced CD8+ T cell exhaustion and upregulated PD-L1 expression. The metabolomic analysis indicated that CHSY1 promoted CD8+ T cell exhaustion by activating the succinate metabolism pathway leading to liver metastasis of CRC. Artemisinin as a CHSY1 inhibitor reduced liver metastasis and enhanced the effect of anti-PD1 in CRC. PLGA-loaded Artemisinin and ICG probe reduced liver metastasis and increased the efficiency of anti-PD1 treatment in CRC. CONCLUSION: CHSY1 could promote CD8+ T cell exhaustion through activation of the succinate metabolic and PI3K/AKT/HIF1A pathway, leading to CRC liver metastasis. The combination of CHSY1 knockdown and anti-PD1 contributes to synergistic resistance to CRC liver metastasis. Artemisinin significantly inhibits CHSY1 activity and in combination with anti-PD1 could synergistically treat CRC liver metastases. This study provides new targets and specific strategies for the treatment of CRC liver metastases, bringing new hope and benefits to patients.

Characterization of Nanoemulsions Stabilized with Different Emulsifiers and Their Encapsulation Efficiency for Oregano Essential Oil: Tween 80, Soybean Protein Isolate, Tea Saponin, and Soy Lecithin.

The use of the appropriate emulsifier is essential for forming a stable nanoemulsion delivery system that can maintain the sustained release of its contents. Health concerns have prompted the search for natural biopolymers to replace traditional synthetic substances as emulsifiers. In this study, an oregano essential oil (OEO) nanoemulsion-embedding system was created using soybean protein isolate (SPI), tea saponin (TS), and soy lecithin (SL) as natural emulsifiers and then compared to a system created using a synthetic emulsifier (Tween 80). The results showed that 4% Tween 80, 1% SPI, 2% TS, and 4% SL were the optimal conditions. Subsequently, the influence of emulsifier type on nanoemulsion stability was evaluated. The results revealed that among all the nanoemulsions, the TS nanoemulsion exhibited excellent centrifugal stability, storage stability, and oxidative stability and maintained high stability and encapsulation efficiency, even under relatively extreme environmental conditions. The good stability of the TS nanoemulsion may be due to the strong electrostatic repulsion generated by TS molecules, which contain hydroxyl groups, sapogenins, and saccharides in their structures. Overall, the natural emulsifiers used in our study can form homogeneous nanoemulsions, but their effectiveness and stability differ considerably.

Dual-mode DNA walker-based optical fiber biosensor for ultrasensitive detection of microRNAs.

We present a novel dual-mode DNA-walker based optical fiber biosensor (DMDW-Opt biosensor) for sensitive assay of micro-RNAs in bio-samples. In the sensor system, we develop a new strategy for the cascade amplification, DNA-walker/rolling cycle amplification (RCA), by the use of the residue track of the walker. The strategy can significantly improve the response of the sensor and avoid any tedious operation procedure. Dual-mode readouts, i.e., fluorescence and chemiluminescence, are measured independently without interfering with each other to achieve reliable and accurate analysis. Optical fibers with the surface modified by gold nanoparticles are utilized as the support for fabrication of the sensor, which would be benefit for developing miniaturized and portable sensing devices. The performance of the proposed method is evaluated by using micro-RNAs (MiR-155 and MiR-21) as the analytical target. The method is successfully applied for accurate determination of micoRNAs in human serum and MCF-7 cells. Our method can perform sensitive assays of MiR-155 with limit-of-detection as low as 97.72 fM and 11.22 fM, MiR-21 with limit-of-detection as low as 107.15 fM and 8.32 fM for the fluorescence- and the chemiluminescence-readout respectively, and the biosensor exhibits excellent specificity, reproducibility and storage stability, indicating its valuable potential applications for sensing trace-amount targets in complicated real samples.

Chemical index components and quality control of Traditional Chinese Medicine: "Never change a winning team"? -A case study of volatile oil from Bupleuri radix.

Chemical index components, especially those defined as quality control (QC) markers through spectrum-effect relationship approach, are commonly suggested and adopted as indicator for quality control of Traditional Chinese Medicines (TCMs). However, are chemical index components and quality control of TCMs "never change a winning team"? In this study, under the ponderation of the applicability of QC markers strategy, spectrum-effect relationship and OPLS-DA between GC×GC-MS fingerprint and inhibitory effect on the expression of extracellular secretory TNF-α of volatile oil from Bupleuri radix (BVO) was studied with the purpose of discovery of QC markers and establish a bioactive compounds-based QC method. 290 compounds of BVO were identified by GC×GC-MS. Besides, BVO had significant inhibitory effects on the expression of extracellular secretory TNF-α in a dose-dependent manner. The potency of different batches of BVOs could be distinguished with this bioassay-based method, which has been validated in terms of intermediate precision, repeatability, linearity, range and credibility tests. The QC markers of BVO were investigated by Spearman's correlation test and OPLS-DA. It is regrettable that there were no ideal QC markers of BVO could be found. In conclusion, quality control method relayed on chemical QC markers is not feasible for TCMs with complex composition but lack of ingredients that dominate in content, just like BVO. Alternatively, a bioassay-based method established in our study is suitable for quality control of BVO.

Afatinib combined with anti-PD1 enhances immunotherapy of hepatocellular carcinoma via ERBB2/STAT3/PD-L1 signaling.

Background: Afatinib is mainly used to treat advanced non-small cell lung cancer, but its therapeutic effect on hepatocellular carcinoma is still unclear. Methods: Over 800 drugs were screened by CCK8 technology and afatinib was found to have a significant inhibitory effect on liver cancer cells. The expression of PDL1 in tumor cells treated with drugs were detected by qRT-PCR and Weston Blot experiments. The effects of afatinib on the growth, migration and invasion of HCC cells were evaluated using wound healing, Transwell, and cell cloning assays. The in vivo effects of afatinib in combination with anti-PD1 were evaluated in C57/BL6J mice with subcutaneous tumorigenesis. Bioinformatics analysis was performed to explore the specific mechanism of afatinib's inhibition of ERBB2 in improving the expression level of PD-L1, which was subsequently verified through experiments. Results: Afatinib was found to have a significant inhibitory effect on liver cancer cells, as confirmed by in vitro experiments, which demonstrated that it could significantly suppress the growth, invasion and migration of HCC cells. qRT PCR and Weston Blot experiments also showed that Afatinib can enhance the expression of PD-L1 in tumor cells. In addition, in vitro experiments confirmed that afatinib can significantly enhance the immunotherapeutic effect of hepatocellular carcinoma. Afatinib's ability to increase PD-L1 expression is mediated by STAT3 activation following its action on HCC cells. Conclusion: Afatinib enhances PD-L1 expression in tumor cells through the STAT3/PD-L1 pathway. The combination of afatinib and anti-PD1 treatment significantly increases the immunotherapeutic effect of HCC.

Activation of Kupffer cells in NAFLD and NASH: mechanisms and therapeutic interventions.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are emerging as the leading causes of liver disease worldwide. These conditions can lead to cirrhosis, liver cancer, liver failure, and other related ailments. At present, liver transplantation remains the sole treatment option for end-stage NASH, leading to a rapidly growing socioeconomic burden. Kupffer cells (KCs) are a dominant population of macrophages that reside in the liver, playing a crucial role in innate immunity. Their primary function includes phagocytosing exogenous substances, presenting antigens, and triggering immune responses. Moreover, they interact with other liver cells during the pathogenesis of NAFLD, and this crosstalk may either delay or exacerbate disease progression. Stimulation by endogenous signals triggers the activation of KCs, resulting in the expression of various inflammatory factors and chemokines, such as NLRP3, TNF-α, IL-1B, and IL-6, and contributing to the inflammatory cascade. In the past 5 years, significant advances have been made in understanding the biological properties and immune functions of KCs in NAFLD, including their interactions with tissue molecules, underlying molecular mechanisms, signaling pathways, and relevant therapeutic interventions. Having a comprehensive understanding of these mechanisms and characteristics can have enormous potential in guiding future strategies for the prevention and treatment of NAFLD.

Nerve growth factor mediates activation of transient receptor potential vanilloid 1 in neurogenic pruritus of psoriasis.

Pruritus is a common and painful symptom in psoriasis with profoundly negative impacts on quality of life. The underlying mechanisms of pruritus are complex and multifactorial, and accumulating evidence suggests that pruritus induced by neurogenic inflammation predominates in psoriasis. Nerve growth factor (NGF) -mediated transient receptor potential vanilloid receptor 1(TRPV1) pathway has emerged as a crucial node in the regulation of neurogenic pruritus. TRPV1 appears coupled to most pruritus-specific molecules via the neuro-immune axis. While the modes of regulation differ for each axis, TRPV1 is involved in substantial biochemical crosstalk-causing feedback loops with significant effects on neurogenic pruritus. Therefore, TRPV1 has emerged as a target molecular in drug development for pruritus in psoriasis. However, no significant clinical progress occurred in the development of systemic TRPV1 antagonists due to elevated core temperature. Thus, topical application of TRPV1 antagonists and interference with mediators linked to the TRPV1 activation pathway may be promising therapeutic options to ameliorate pruritus. This Review focuses on recent advances in complicated regulation of NGF-mediated TRPV1 pathway in psoriatic neurogenic pruritus, as well as the therapeutic options that arise from the dissection of the pathway.

Oncogenic role and potential regulatory mechanism of fatty acid binding protein 5 based on a pan-cancer analysis.

As one member of fatty acid binding proteins (FABPs), FABP5 makes a contribution in the occurrence and development of several tumor types, but existing analysis about FABP5 and FABP5-related molecular mechanism remains limited. Meanwhile, some tumor patients showed limited response rates to current immunotherapy, and more potential targets need to be explored for the improvement of immunotherapy. In this study, we made a pan-cancer analysis of FABP5 based on the clinical data from The Cancer Genome Atlas database for the first time. FABP5 overexpression was observed in many tumor types, and was statistically associated with poor prognosis of several tumor types. Additionally, we further explored FABP5-related miRNAs and corresponding lncRNAs. Then, miR-577-FABP5 regulatory network in kidney renal clear cell carcinoma as well as CD27-AS1/GUSBP11/SNHG16/TTC28-AS1-miR-22-3p-FABP5 competing endogenous RNA regulatory network in liver hepatocellular carcinoma were constructed. Meanwhile, Western Blot and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) analysis were used to verify miR-22-3p-FABP5 relationship in LIHC cell lines. Moreover, the potential relationships of FABP5 with immune infiltration and six immune checkpoints (CD274, CTLA4, HAVCR2, LAG3, PDCD1 and TIGIT) were discovered. Our work not only deepens the understanding of FABP5's functions in multiple tumors and supplements existing FABP5-related mechanisms, but also provides more possibilities for immunotherapy.

Laparoscopic versus open repeat hepatectomy for recurrent hepatocellular carcinoma: a systematic review and meta-analysis of propensity score-matched cohort studies.

OBJECTIVE: The effectiveness of laparoscopic repeat hepatectomy (LRH) versus open repeat hepatectomy (ORH) on recurrent hepatocellular carcinoma (RHCC) is unclear. We compared the surgical and oncological outcomes of LRH and ORH in patients with RHCC with a meta-analysis of studies based on propensity score-matched cohorts. METHODS: A literature search was conducted on PubMed, Embase, and Cochrane Library with Medical Subject Headings terms and keywords until 30 September 2022. The quality of eligible studies was evaluated with the Newcastle-Ottawa Scale. Mean difference (MD) with a 95% CI was used for the analysis of continuous variables; odds ratio (OR) with 95% CI was used for binary variables; and hazard ratio with 95% CI was used for survival analysis. A random-effects model was used for meta-analysis. RESULTS: Five high-quality retrospective studies with 818 patients were included; 409 patients (50%) were treated with LRH and 409 (50%) with ORH. In most surgical outcomes, LRH was superior to ORH: less estimated blood loss, shorter operation time, lower major complication rate, and shorter length of hospital stay (MD=-225.9, 95% CI=[-360.8 to -91.06], P =0.001; MD=66.2, 95% CI=[5.28-127.1], P =0.03; OR=0.18, 95% CI=[0.05-0.57], P =0.004; MD=-6.22, 95% CI=[-9.78 to -2.67], P =0.0006). There were no significant differences in the remaining surgical outcomes: blood transfusion rate and overall complication rate. In oncological outcomes, LRH and ORH were not significantly different in 1-year, 3-year, and 5-year overall survival and disease-free survival. CONCLUSIONS: For patients with RHCC, most surgical outcomes with LRH were superior to those of ORH, but oncological outcomes with the two operations were similar. LRH may be a preferable option for the treatment of RHCC.

Proteomic Profiling of Colorectal Adenomas Identifies a Predictive Risk Signature for Development of Metachronous Advanced Colorectal Neoplasia.

BACKGROUND & AIMS: Colonic adenomatous polyps, or adenomas, are frequent precancerous lesions and the origin of most cases of colorectal adenocarcinoma. However, we know from epidemiologic studies that although most colorectal cancers (CRCs) originate from adenomas, only a small fraction of adenomas (3%-5%) ever progress to cancer. At present, there are no molecular markers to guide follow-up surveillance programs. METHODS: We profiled, by mass spectrometry-based proteomics combined with machine learning analysis, a selected cohort of formalin-fixed, paraffin-embedded high-grade (HG) adenomas with long clinical follow-up, collected as part of the Danish national screening program. We grouped subjects in the cohort according to their subsequent history of findings: a nonmetachronous advanced neoplasia group (G0), with no new HG adenomas or CRCs up to 10 years after polypectomy, and a metachronous advanced neoplasia group (G1) where individuals developed a new HG adenoma or CRC within 5 years of diagnosis. RESULTS: We generated a proteome dataset from 98 selected HG adenoma samples, including 20 technical replicates, of which 45 samples belonged to the nonmetachronous advanced neoplasia group and 53 to the metachronous advanced neoplasia group. The clear distinction of these 2 groups seen in a uniform manifold approximation and projection plot indicated that the information contained within the abundance of the ∼5000 proteins was sufficient to predict the future occurrence of HG adenomas or development of CRC. CONCLUSIONS: We performed an in-depth analysis of quantitative proteomic data from 98 resected adenoma samples using various novel algorithms and statistical packages and found that their proteome can predict development of metachronous advanced lesions and progression several years in advance.

Minimal-access video-assisted retroperitoneal and/or transperitoneal debridement (VARTD) in the management of infected walled-off pancreatic necrosis with deep extension: initial experience from a prospective single-arm study.

BACKGROUND: The currently preferred minimally invasive approaches have substantially improved outcomes of infected walled-off pancreatic necrosis (iWON). However, iWON with deep extension (iWONde) still poses a tricky challenge for sufficient necrosis evacuation by one stand-alone approach, often requiring repeated interventions. The aim of this study was to assess the effectiveness and safety of a minimal-access video-assisted retroperitoneal and/or transperitoneal debridement (hereafter called VARTD) in the management of iWONde. METHODS: Patients who had developed an iWONde were recruited to receive the VARTD in this prospective single-arm study. The primary efficacy endpoint was clinical improvement up to day 28 after the VARTD, defined as a ≥ 75% reduction in size of necrotic collection (in any axis) on CT and clinical resolution of sepsis or organ dysfunction. The primary safety endpoint was a composite of major complications or death during follow-up. Six-month postdischarge follow-up was available. RESULTS: Between July 18, 2018, and November 12, 2020, we screened 95 patients with necrotizing pancreatitis; of these, 21 iWONde patients (mean [SD] age, 42.9 [11.7] years; 10 [48%] women) were finally enrolled. The primary efficacy endpoint was achieved by most participants (14/21, 67%). No participants required repeated interventions. The primary safety endpoint occurred in six patients (29%). Except one in-hospital death attributable to repeated intra-abdominal hemorrhage, others were discharged without any major complication. CONCLUSIONS: The VARTD approach appears to have a reasonable efficacy with acceptable complication rates and thus might be an option for improving clinical management of iWONde. TRIAL REGISTRATION: This study is registered with Chinese Clinical Trial Registry (chictr.org.cn number, ChiCTR1800016950).

Challenges and Prospects in the Catalytic Conversion of Carbon Dioxide to Formaldehyde.

Formaldehyde (HCHO) is a crucial C1 building block for daily-life commodities in a wide range of industrial processes. Industrial production of HCHO today is based on energy- and cost-intensive gas-phase catalytic oxidation of methanol, which calls for exploring other and more sustainable ways of carrying out this process. Utilization of carbon dioxide (CO2 ) as precursor presents a promising strategy to simultaneously mitigate the carbon footprint and alleviate environmental issues. This Minireview summarizes recent progress in CO2 -to-HCHO conversion using hydrogenation, hydroboration/hydrosilylation as well as photochemical, electrochemical, photoelectrochemical, and enzymatic approaches. The active species, reaction intermediates, and mechanistic pathways are discussed to deepen the understanding of HCHO selectivity issues. Finally, shortcomings and prospects of the various strategies for sustainable reduction of CO2 to HCHO are discussed.