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1.
Front Oncol ; 14: 1297153, 2024.
Article in English | MEDLINE | ID: mdl-38720805

ABSTRACT

Purpose: This study aims to evaluate the efficacy and safety of ultrasound-guided percutaneous biopsy of the first hepatic hilum lesion, and examine its clinical value of diagnosis and treatment. Methods: We conducted a retrospective study on patients diagnosed with the first hepatic hilum lesions at Fujian Provincial Hospital between February 2015 and October 2022. We selected patients who had lesions in the first hepatic hilum(including a 2cm surrounding area of the left/right hepatic ducts and upper-middle segment of the common bile duct) and the liver periphery(in the peripheral area of the liver, outside of the above-mentioned first hepatic porta region). These patients underwent percutaneous ultrasound-guided core needle biopsy (PUS-CNB) with cognitive fusion guidance using CT, MRI, or PET-CT. We compared the safety and efficacy of PUS-CNB in the first hepatic hilum and the liver periphery to explore the value of PUS-CNB in optimizing the clinical treatment of the first hepatic hilum lesions. Results: The studied includes 38 cases of the first hepatic hilum cases (18 females; 20 males), 23 presented with mass-forming tumors while the remaining 15 exhibited diffuse infiltrative tumors, with an average diameter of 4.65± 2.51 cm. The percutaneous biopsy procedure, conducted under ultrasound guidance, had an average operation time of 14.55 ± 2.73 minutes, and resulted in a postoperative bleeding volume of approximately 10.79 ± 2.79 ml. The diagnostic success rate was noted to be as high as 92.11% among the participants who underwent percutaneous biopsy of the first hepatic hilum. Procedural complications, such as bleeding, bile leakage, intestinal perforation, infection or needle tract seeding, did not occur during or after the biopsy procedure. Affected by biopsy results, 5 altered their clinical treatment plans accordingly, 24patients received non-surgical treatment, 9 underwent surgical treatment, 5 underwent radiofrequency ablation for the lesions. The study comprised a total of 112 cases for percutaneous biopsy of the liver periphery. The safety and effectiveness of the two biopsy techniques were comparable, with diagnostic success rates of 92.11% VS. 94.34%, respectively (p = 0.61). Conclusion: Cognitive fusion of ultrasound and multi-modal imaging for the first hepatic hilum lesion puncture biopsy is a safe and effective diagnostic procedure, with better diagnostic rate, may improve clinical value of diagnosis and treatment of various diseases.

2.
J Hazard Mater ; 470: 134135, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38574656

ABSTRACT

Sb(III) and As(III) share similar chemical features and coexist in the environment. However, their oxidase enzymes have completely different sequences and structures. This raises an intriguing question: Could Sb(III)-oxidizing prokaryotes (SOPs) also oxidize As(III), and vice versa? Regarding this issue, previous investigations have yielded unclear, incorrect and even conflicting data. This work aims to address this matter. First, we prepared an enriched population of SOPs that comprises 55 different AnoA genes, lacking AioAB and ArxAB genes. We found that these SOPs can oxidize both Sb(III) and As(III) with comparable capabilities. To further confirm this finding, we isolated three cultivable SOP strains that have AnoA gene, but lack AioAB and ArxAB genes. We observed that they also oxidize both Sb(III) and As(III) under both anaerobic and aerobic conditions. Secondly, we obtained an enriched population of As(III)-oxidizing prokaryotes (AOPs) from As-contaminated soils, which comprises 69 different AioA genes, lacking AnoA gene. We observed that the AOP population has significant As(III)-oxidizing activities, but lack detectable Sb(III)-oxidizing activities under both aerobic and anaerobic conditions. Therefore, we convincingly show that SOPs can oxidize As(III), but AOPs cannot oxidize Sb(III). These findings clarify the previous ambiguities, confusion, errors or contradictions regarding how SOPs and AOPs oxidize each other's substrate.


Subject(s)
Antimony , Oxidation-Reduction , Anaerobiosis , Aerobiosis , Antimony/metabolism , Prokaryotic Cells/metabolism , Soil Microbiology , Bacteria/metabolism , Bacteria/genetics , Soil Pollutants/metabolism
3.
Angew Chem Int Ed Engl ; : e202402497, 2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38679571

ABSTRACT

The large size of K-ion makes the pursuit of stable high-capacity anodes for K-ion batteries (KIBs) a formidable challenge, particularly for high temperature KIBs as the electrode instability becomes more aggravated with temperature climbing. Herein, we demonstrate that a hollow ZnS@C nanocomposite (h-ZnS@C) with a precise shell modulation can resist electrode disintegration to enable stable high-capacity potassium storage at room and high temperature. Based on a model electrode, we identify an interesting structure-function correlation of the h-ZnS@C: with an increase in the shell thickness, the cyclability increases while the rate and capacity decreases, shedding light on the design of high-performance h-ZnS@C anodes via engineering the shell thickness. Typically, the h-ZnS@C anode with a shell thickness of 60 nm can deliver an impressive comprehensive performance at room temperature; the h-ZnS@C with shell thickness increasing to 75 nm can achieve an extraordinary stability (88.6% capacity retention over 450 cycles) with a high capacity (450 mAh g-1) and a superb rate even at an extreme temperature of 60 ℃, which is much superior than those reported anodes. This contribution envisions new perspectives on rational design of functional metal sulfides composite toward high-performance KIBs with insights into the significant structure-function correlation.

4.
Angew Chem Int Ed Engl ; : e202403073, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38567830

ABSTRACT

Catalytic methods allowing for the reliable prediction and control of diverse regioselectivity along with the control of enantioselectivity to access different regio- and enantiomers by switching the least reaction parameters are one of the most attractive ways in organic synthesis, which provide access to diverse enantioenriched architectures from identical starting materials. Herein, a Co-catalyzed regiodivergent and enantioselective reductive hydroalkylation of 1,3-dienes with aldehydes has been achieved, furnishing different enantioenriched homoallylic alcohol architectures in good levels of enantioselectivity. The reaction features the switch of regioselectivity tuned by the selection of proton source. The use of an acid as proton source provided asymmetric 1,2-hydroalkylation products under reductive conditions, yet asymmetric 4,3-hydroalkylation products were obtained with silane as hydride source. This catalytic protocol allows for the access of homoallylic alcohols with two continuous saturated carbon centers in good levels of regio-, diastereo-, and enantioselectivity.

5.
BMC Public Health ; 24(1): 891, 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38528465

ABSTRACT

BACKGROUND: Bladder, kidney and prostate cancers make significant contributors to cancer burdens. Exploring their cross-country inequalities may inform equitable strategies to meet the 17 sustainable development goals before 2030. METHODS: We analyzed age-standardized disability-adjusted life-years (ASDALY) rates for the three cancers based on Global Burden of Diseases Study 2019. We quantified the inequalities using slope index of inequality (SII, absolute measure) and concentration index (relative measure) associated with national sociodemographic index. RESULTS: Varied ASDALY rates were observed in the three cancers across 204 regions. The SII decreased from 35.15 (95% confidence interval, CI: 29.34 to 39.17) in 1990 to 15.81 (95% CI: 7.99 to 21.79) in 2019 for bladder cancers, from 78.94 (95% CI: 75.97 to 81.31) in 1990 to 59.79 (95% CI: 55.32 to 63.83) in 2019 for kidney cancer, and from 192.27 (95% CI: 137.00 to 241.05) in 1990 to - 103.99 (95% CI: - 183.82 to 51.75) in 2019 for prostate cancer. Moreover, the concentration index changed from 12.44 (95% CI, 11.86 to 12.74) in 1990 to 15.72 (95% CI, 15.14 to 16.01) in 2019 for bladder cancer, from 33.88 (95% CI: 33.35 to 34.17) in 1990 to 31.13 (95% CI: 30.36 to 31.43) in 2019 for kidney cancer, and from 14.61 (95% CI: 13.89 to 14.84) in 1990 to 5.89 (95% CI: 5.16 to 6.26) in 2019 for prostate cancer. Notably, the males presented higher inequality than females in both bladder and kidney cancer from 1990 to 2019. CONCLUSIONS: Different patterns of inequality were observed in the three cancers, necessitating tailored national cancer control strategies to mitigate disparities. Priority interventions for bladder and kidney cancer should target higher socioeconomic regions, whereas interventions for prostate cancer should prioritize the lowest socioeconomic regions. Additionally, addressing higher inequality in males requires more intensive interventions among males from higher socioeconomic regions.


Subject(s)
Kidney Neoplasms , Prostatic Neoplasms , Male , Humans , Socioeconomic Factors , Global Burden of Disease , Urinary Bladder , Cost of Illness , Kidney Neoplasms/epidemiology , Kidney , Prostatic Neoplasms/epidemiology
6.
Int Immunopharmacol ; 131: 111899, 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38513576

ABSTRACT

The prevalence rate of allergic diseases including asthma, atopic rhinitis (AR) and atopic dermatitis (AD) has been significantly increasing in recent decades due to environmental changes and social developments. With the study of innate lymphoid cells, the crucial role played by type 2 innate lymphoid cells (ILC2s) have been progressively unveiled in allergic diseases. ILC2s, which are a subset of innate lymphocytes initiate allergic responses. They respond swiftly during the onset of allergic reactions and produce type 2 cytokines, working in conjunction with T helper type 2 (Th2) cells to induce and sustain type 2 immune responses. The role of ILC2s represents an intriguing frontier in immunology; however, the intricate immune mechanisms of ILC2s in allergic responses remain relatively poorly understood. To gain a comphrehensive understanding of the research progress of ILC2, we summarize recent advances in ILC2s biology in pathologic allergic inflammation to inspire novel approaches for managing allergic diseases.


Subject(s)
Immunity, Innate , Rhinitis, Allergic , Humans , Lymphocytes , Cytokines , Inflammation
7.
JMIR Med Inform ; 12: e49138, 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38297829

ABSTRACT

Background: Although evidence-based medicine proposes personalized care that considers the best evidence, it still fails to address personal treatment in many real clinical scenarios where the complexity of the situation makes none of the available evidence applicable. "Medicine-based evidence" (MBE), in which big data and machine learning techniques are embraced to derive treatment responses from appropriately matched patients in real-world clinical practice, was proposed. However, many challenges remain in translating this conceptual framework into practice. Objective: This study aimed to technically translate the MBE conceptual framework into practice and evaluate its performance in providing general decision support services for outcomes after congenital heart disease (CHD) surgery. Methods: Data from 4774 CHD surgeries were collected. A total of 66 indicators and all diagnoses were extracted from each echocardiographic report using natural language processing technology. Combined with some basic clinical and surgical information, the distances between each patient were measured by a series of calculation formulas. Inspired by structure-mapping theory, the fusion of distances between different dimensions can be modulated by clinical experts. In addition to supporting direct analogical reasoning, a machine learning model can be constructed based on similar patients to provide personalized prediction. A user-operable patient similarity network (PSN) of CHD called CHDmap was proposed and developed to provide general decision support services based on the MBE approach. Results: Using 256 CHD cases, CHDmap was evaluated on 2 different types of postoperative prognostic prediction tasks: a binary classification task to predict postoperative complications and a multiple classification task to predict mechanical ventilation duration. A simple poll of the k-most similar patients provided by the PSN can achieve better prediction results than the average performance of 3 clinicians. Constructing logistic regression models for prediction using similar patients obtained from the PSN can further improve the performance of the 2 tasks (best area under the receiver operating characteristic curve=0.810 and 0.926, respectively). With the support of CHDmap, clinicians substantially improved their predictive capabilities. Conclusions: Without individual optimization, CHDmap demonstrates competitive performance compared to clinical experts. In addition, CHDmap has the advantage of enabling clinicians to use their superior cognitive abilities in conjunction with it to make decisions that are sometimes even superior to those made using artificial intelligence models. The MBE approach can be embraced in clinical practice, and its full potential can be realized.

8.
Front Immunol ; 15: 1348272, 2024.
Article in English | MEDLINE | ID: mdl-38361946

ABSTRACT

The epithelial barrier serves as a critical defense mechanism separating the human body from the external environment, fulfilling both physical and immune functions. This barrier plays a pivotal role in shielding the body from environmental risk factors such as allergens, pathogens, and pollutants. However, since the 19th century, the escalating threats posed by environmental pollution, global warming, heightened usage of industrial chemical products, and alterations in biodiversity have contributed to a noteworthy surge in allergic disease incidences. Notably, allergic diseases frequently exhibit dysfunction in the epithelial barrier. The proposed epithelial barrier hypothesis introduces a novel avenue for the prevention and treatment of allergic diseases. Despite increased attention to the role of barrier dysfunction in allergic disease development, numerous questions persist regarding the mechanisms underlying the disruption of normal barrier function. Consequently, this review aims to provide a comprehensive overview of the epithelial barrier's role in allergic diseases, encompassing influencing factors, assessment techniques, and repair methodologies. By doing so, it seeks to present innovative strategies for the prevention and treatment of allergic diseases.


Subject(s)
Hypersensitivity , Humans , Allergens
9.
J Am Chem Soc ; 146(10): 6753-6762, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38412236

ABSTRACT

High-temperature rechargeable batteries are essential for energy storage in elevated-temperature situations. Due to the resource abundance of potassium, high-temperature K-ion batteries are drawing increasing research interest. However, raising the working temperature would aggravate the chemical and mechanical instability of the KIB anode, resulting in very fast capacity fading, especially when high capacity is pursued. Here, we demonstrated that a porous conductive metal-organic framework (MOF), which is constructed by N-rich aromatic molecules and CuO4 units via π-d conjugation, could provide multiple accessible redox-active sites and promised robust structure stability for efficient potassium storage at high temperatures. Even working at 60 °C, this MOF anode could deliver high initial capacity (455 mAh g-1), impressive rate, and extraordinary cyclability (96.7% capacity retention for 1600 cycles), which is much better than those of reported high-temperature KIB anodes. The mechanistic study revealed that C═N groups and CuO4 units contributed abundant redox-active sites; the synergistic effect of π-d conjugated character and reticular porous architecture facilitated the K+/e- transport and ensured an insoluble electrode with small volume deformation, thus achieving stable high-capacity potassium storage.

10.
Angew Chem Int Ed Engl ; 63(15): e202400012, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38340327

ABSTRACT

Hollow nanoporous carbon architectures (HNCs) present significant utilitarian value for a wide variety of applications. Facile and efficient preparation of HNCs has long been pursued but still remains challenging. Herein, we for the first time demonstrate that single-component metal-organic frameworks (MOFs) crystals, rather than the widely reported hybrid ones which necessitate tedious operations for preparation, could enable the facile and versatile syntheses of functional HNCs. By controlling the growth kinetics, the MOFs crystals (STU-1) are readily engineered into different shapes with designated styles of crystalline inhomogeneity. A subsequent one-step pyrolysis of these MOFs with intraparticle difference can induce a simultaneous self-hollowing and carbonization process, thereby producing various functional HNCs including yolk-shell polyhedrons, hollow microspheres, mesoporous architectures, and superstructures. Superior to the existing methods, this synthetic strategy relies only on the complex nature of single-component MOFs crystals without involving tedious operations like coating, etching, or ligand exchange, making it convenient, efficient, and easy to scale up. An ultra-stable Na-ion battery anode is demonstrated by the HNCs with extraordinary cyclability (93 % capacity retention over 8000 cycles), highlighting a high level of functionality of the HNCs.

11.
Prostate ; 84(6): 570-583, 2024 May.
Article in English | MEDLINE | ID: mdl-38328967

ABSTRACT

BACKGROUNDS: The study aimed to analyze epidemiology burden of male prostate cancer across the BRICS-plus, and identify potential risk factors by assessing the associations with age, period, birth cohorts and sociodemographic index (SDI). METHODS: Data were extracted from the Global Burden of Disease Study 2019. The average annual percent change (AAPC) was calculated to assess long-term trends, and age-period-cohort analysis was used to analyze these three effects on prostate cancer burden. Quantile regression was used to investigate the association between SDI and health outcomes. RESULTS: The higher incidence and mortality were observed in Mercosur and SACU regions, increasing trends were observed in prostate cancer incidence in almost all BRICS-plus countries (AAPC > 0), and EEU's grew by 24.31% (%AAPC range: -0.13-3.03). Mortality had increased in more than half of countries (AAPC > 0), and SACU grew by 1.82% (%AAPC range: 0.62-1.75). Incidence and mortality risk sharply increased with age across all BRICS-plus countries and globally, and the peak was reached in the age group 80-84 years. Rate ratio (RR) of incidence increased with birth cohorts in all BRICS-plus countries except for Kazakhstan where slightly decrease, while mortality RR decreased with birth cohort in most of BRICS-plus countries. SDI presented significantly positive associations with incidence in 50 percentiles. The deaths attributable to smoking declined in most of BRICS-plus nations, and many countries in China-ASEAN-FTA and EEU had higher values. CONCLUSION: Prostate cancer posed a serious public health challenge with an increasing burden among most of BRICS-plus countries. Age had significant effects on prostate cancer burden, and recent birth cohorts suffered from higher incidence risk. SDI presented a positive relationship with incidence, and the smoking-attributable burden was tremendous in China-ASEAN-FTA and EEU region. Secondary prevention should be prioritized in BRICS-plus nations, and health policies targeting important populations should be strengthened based on their characteristics and adaptability.


Subject(s)
Global Burden of Disease , Prostatic Neoplasms , Humans , Male , Aged, 80 and over , Risk Factors , Smoking/adverse effects , Smoking/epidemiology , China/epidemiology , Prostatic Neoplasms/epidemiology
12.
Chemosphere ; 352: 141385, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38316280

ABSTRACT

Antimony (Sb) and arsenic (As) share similar chemical characteristics and commonly coexist in contaminated environments. It has been reported that the biogeochemical cycles of antimony and arsenic affect each other. However, there is limited understanding regarding microbial coupling between the biogeochemical processes of antimony and arsenic. Here, we aimed to solve this issue. We successfully isolated a novel bacterium, Shinella sp. SbAsOP1, which possesses both Sb(III) and As(III) oxidase, and can effectively oxidize both Sb(III) and As(III) under aerobic and anaerobic conditions. SbAsOP1 exhibits greater aerobic oxidation activity for the oxidation of As(III) or Sb(III) compared to its anaerobic activity. SbAsOP1 also significantly catalyzes the oxidative mobilization of solid-phase Sb(III) under aerobic conditions. The activity of SbAsOP1 in oxidizing solid Sb(III) is 3 times lower than its activity in oxidizing soluble form. It is noteworthy that, in the presence of both Sb(III) and As(III) under aerobic conditions, either As(III) or Sb(III) significantly inhibits the oxidation of Sb(III) or As(III), respectively. In comparison, under anaerobic conditions and in the coexistence of Sb(III) and As(III), As(III) significantly inhibits Sb(III) oxidation, whereas Sb(III) almost completely inhibits As(III) oxidation. These findings suggest that under both aerobic and anaerobic conditions, SbAsOP1 demonstrates a partial preference for Sb(III) oxidation. Additionally, bacterial oxidations of Sb(III) and As(III) mutually inhibit each other to varying degrees. These observations gain a novel understanding of the interplay between the biogeochemical processes of antimony and arsenic.


Subject(s)
Arsenic , Rhizobiaceae , Arsenic/metabolism , Antimony , Oxidation-Reduction , Oxidoreductases/metabolism , Rhizobiaceae/metabolism
13.
ACS Nano ; 18(6): 5003-5016, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38294411

ABSTRACT

The cycling stability of a thin zinc anode under high zinc utilization has a critical impact on the overall energy density and practical lifetime of zinc ion batteries. In this study, an ion sieve protection layer (ZnSnF@Zn) was constructed in situ on the surface of a zinc anode by chemical replacement. The ion sieve facilitated the transport and desolvation of zinc ions at the anode/electrolyte interface, reduced the zinc deposition overpotential, and inhibited side reactions. Under a 50% zinc utilization, the symmetrical battery with this protection layer maintained stable cycling for 250 h at 30 mA cm-2. Matched with high-load self-supported vanadium-based cathodes (18-20 mg cm-2), the coin battery with 50% zinc utilization possessed an energy density retention of 94.3% after 1000 cycles at 20 mA cm-2. Furthermore, the assembled pouch battery delivered a whole energy density of 61.3 Wh kg-1, surpassing the highest mass energy density among reported mild zinc batteries, and retained 76.7% of the energy density and 85.3% (0.53 Ah) of the capacity after 300 cycles.

14.
Biomedicines ; 12(1)2024 Jan 16.
Article in English | MEDLINE | ID: mdl-38255298

ABSTRACT

The human gut microbiota, comprising trillions of microorganisms residing in the gastrointestinal tract, has emerged as a pivotal player in modulating various aspects of human health and disease. Recent research has shed light on the intricate relationship between the gut microbiota and pharmaceuticals, uncovering profound implications for drug metabolism, efficacy, and safety. This review depicted the landscape of molecular mechanisms and clinical implications of dynamic human gut Microbiota-Drug Interactions (MDI), with an emphasis on the impact of MDI on drug responses and individual variations. This review also discussed the therapeutic potential of modulating the gut microbiota or harnessing its metabolic capabilities to optimize clinical treatments and advance personalized medicine, as well as the challenges and future directions in this emerging field.

15.
ACS Appl Mater Interfaces ; 16(4): 5234-5244, 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38241202

ABSTRACT

The electromagnetic (EM) beam manipulations such as spatial scanning have always been the focus in information science and technology. Generally, the transmitting and receiving (T/R) beams of the same aperture should be coincident due to the reciprocal theory, and hence, more flexible controls of the spatial information are limited accordingly. Here, we propose a new approach to achieve independent controls of beam scanning in spatial T/R channels based on one aperture made by a nonreciprocal programmable metasurface. The meta-atom is designed to have independent propagation chains for T/R waves by introducing dual-direction power amplifiers (PAs) as the isolators for one-way transparency. A programmable phase shifter with a 360° coverage is loaded with the PA device in the transmitting or receiving chain to realize independent beam scanning in the T/R channels. A prototype of the proposed metasurface is fabricated, and independent beam scanning in the T/R channels is directly acquired with good performance in our measurements. In addition, a proof of concept of integrated sensing and auxiliary communications is accomplished to verify the validity of the presented method.

17.
Int J Clin Pharmacol Ther ; 62(3): 115-121, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38263810

ABSTRACT

OBJECTIVE: To evaluate the efficacy, safety, and economics of mecapegfilgrastim and recombinant human granulocyte colony-stimulating factor (rhG-CSF) in the primary prevention of chemotherapy-related neutropenia in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Data from 181 patients with NSCLC who received intermediate risk chemotherapy were collected from the information system of a tertiary hospital in China. Patients were categorized into two groups: those treated with mecapegfilgrastim (n = 91) and those treated with rhG-CSF (n = 90). The clinical efficacy rates of neutropenia prevention were used as effect indicators, and a cost-effectiveness analysis was conducted from the perspective of the Chinese healthcare system. Logistic regression, generalized linear regression, and bootstrap methods were used for sensitivity analyses. RESULTS: There was no statistical difference between the mecapegfilgrastim and rhG-CSF groups in clinical efficacy rates (98.9 vs. 97.8%). However, the total cost in the mecapegfilgrastim group was significantly higher than that in the rhG-CSF group (16,341.6 CNY vs. 14,371.1 CNY, p = 0.03). The cost-minimization analysis shows that mecapegfilgrastim is not cost-effective. The sensitivity analyses confirm that these results are robust. CONCLUSION: Compared with rhG-CSF, mecapegfilgrastim is not a cost-effective strategy for NSCLC patients in neutropenia prevention in China.


Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Neutropenia , Polyethylene Glycols , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Cost-Effectiveness Analysis , Neutropenia/chemically induced , Neutropenia/drug therapy , Neutropenia/prevention & control , Granulocyte Colony-Stimulating Factor/therapeutic use , Recombinant Proteins/therapeutic use , Granulocytes , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Agents/adverse effects
18.
Proc Natl Acad Sci U S A ; 121(6): e2304619121, 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38289962

ABSTRACT

Resistance to neoadjuvant chemotherapy leads to poor prognosis of locally advanced rectal cancer (LARC), representing an unmet clinical need that demands further exploration of therapeutic strategies to improve clinical outcomes. Here, we identified a noncanonical role of RB1 for modulating chromatin activity that contributes to oxaliplatin resistance in colorectal cancer (CRC). We demonstrate that oxaliplatin induces RB1 phosphorylation, which is associated with the resistance to neoadjuvant oxaliplatin-based chemotherapy in LARC. Inhibition of RB1 phosphorylation by CDK4/6 inhibitor results in vulnerability to oxaliplatin in both intrinsic and acquired chemoresistant CRC. Mechanistically, we show that RB1 modulates chromatin activity through the TEAD4/HDAC1 complex to epigenetically suppress the expression of DNA repair genes. Antagonizing RB1 phosphorylation through CDK4/6 inhibition enforces RB1/TEAD4/HDAC1 repressor activity, leading to DNA repair defects, thus sensitizing oxaliplatin treatment in LARC. Our study identifies a RB1 function in regulating chromatin activity through TEAD4/HDAC1. It also provides the combination of CDK4/6 inhibitor with oxaliplatin as a potential synthetic lethality strategy to mitigate oxaliplatin resistance in LARC, whereby phosphorylated RB1/TEAD4 can serve as potential biomarkers to guide the patient stratification.


Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Humans , Oxaliplatin/pharmacology , Neoadjuvant Therapy/methods , Rectal Neoplasms/drug therapy , Rectal Neoplasms/genetics , Chemoradiotherapy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chromatin , Treatment Outcome , TEA Domain Transcription Factors , Ubiquitin-Protein Ligases , Retinoblastoma Binding Proteins
19.
Sci Total Environ ; 916: 169893, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38185173

ABSTRACT

Sb and As are chemically similar, but the sequences and structures of Sb(III) and As(III) oxidase are totally distinct. It is thus interesting to explore whether Sb(III) oxidase oxidizes As(III), and if so, how microbial oxidations of Sb(III) and As(III) influence one another. Previous investigations have yielded ambiguous or even erroneous conclusions. This study aimed to clarify this issue. Firstly, we prepared a consortium of Sb(III)-oxidizing prokaryotes (SOPs) by enrichment cultivation. Metagenomic analysis reveals that SOPs with the Sb(III) oxidase gene, but lacking the As(III) oxidase gene are predominant in the SOP community. Despite this, SOPs exhibit comparable Sb(III) and As(III)-oxidizing activities in both aerobic and anaerobic conditions, indicating that at the microbial community level, Sb(III) oxidase can oxidize As(III). Secondly, we isolated a representative cultivable SOP, Ralstonia sp. SbOX with Sb(III) oxidase gene but without As(III) oxidase gene. Genomic analysis of SbOX reveals that this SOP strain has a complete Sb(III) oxidase (AnoA) gene, but lacks As(III) oxidase (AioAB or ArxAB) gene. It is interesting to discover that, besides its Sb(III) oxidation activities, SbOX also exhibits significant capabilities in oxidizing As(III) under both aerobic and anaerobic conditions. Moreover, under aerobic conditions and in the presence of both Sb(III) and As(III), SbOX exhibited a preference for oxidizing Sb(III). Only after the near complete oxidation of Sb(III) did SbOX initiate rapid oxidation of As(III). In contrast, under anaerobic conditions and in the presence of both Sb(III) and As(III), Sb(III) oxidation notably inhibited the As(III) oxidation pathway in SbOX, while As(III) exhibited minimal effects on the Sb(III) oxidation. These findings suggest that SOPs can oxidize As(III) under both aerobic and anaerobic conditions, exhibiting a strong preference for Sb(III) over As(III) oxidation in the presence of both. This study unveils a novel mechanism of interaction within the Sb and As biogeochemical cycles.


Subject(s)
Antimony , Oxidoreductases , Oxidoreductases/metabolism , Anaerobiosis , Antimony/metabolism , Oxidation-Reduction , Bacteria/metabolism
20.
Small ; 20(1): e2304463, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37649191

ABSTRACT

The high activity of water molecules results in a series of awful parasitic reaction, which seriously impede the development of aqueous zinc batteries. Herein, a new gel electrolyte with multiple molecular anchors is designed by employing natural biomaterials from chitosan and chlorophyll derivative. The gel electrolyte firmly anchors water molecules by ternary hydrogen bonding to reduce the activity of water molecules and inhibit hydrogen evolution reaction. Meanwhile, the multipolar charged functional groups realize the gradient induction and redistribution of Zn2+ , which drives oriented Zn (002) plane deposition of Zn2+ and then achieves uniform Zn deposition and dendrite-free anode. As a result, it endows the Zn||Zn cell with over 1700 h stripping/plating processes and a high efficiency of 99.4% for the Zn||Cu cell. In addition, the Zn||V2 O5 full cells also exhibit capacity retention of 81.7% after 600 cycles at 0.5 A g-1 and excellent long-term stability over 1600 cycles at 2 A g-1 , and the flexible pouch cells can provide stable power for light-emitting diodes even after repeated bending. The gel electrolyte strategy provides a reference for reversible zinc anode and flexible wearable devices.

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