Camrelizumab, chemotherapy and apatinib in the neoadjuvant treatment of resectable oesophageal squamous cell carcinoma: a single-arm phase 2 trial.

Background: In resectable oesophageal squamous cell carcinoma (ESCC), the efficacy of camrelizumab combined with chemotherapy and apatinib followed by minimally invasive oesophagectomy is not clear. We aimed to fill this knowledge gap. Methods: This investigator-initiated, single-arm, prospective, phase 2 trial was performed at the Second Affiliated Hospital of Zhejiang University, China. Patients (aged 18-75 years) who were histologically or cytologically diagnosed with ESCC were deemed suitable to participate in this trial. Patients received 2-3 cycles of neoadjuvant therapy with camrelizumab, nedaplatin, albumin paclitaxel, and apatinib; each cycle was repeated every 14 days. Surgery occurred 4-6 weeks after the last neoadjuvant treatment cycle. The primary outcome was the pathological complete response (PCR) rate of the tumour and lymph nodes. The changes in the peripheral blood immunoprofile among patients without PCR (ie, non-PCR [NPCR]) and with PCR were assessed by mass cytometry. This study was registered with ClinicalTrials.gov, NCT04666090. Findings: 42 patients were enrolled between November 23, 2020 and December 31, 2022. The disease control rate was 100.0% (95% CI, 91.6-100%), and the objective response rate was 83.3% (95% CI, 68.6-93.0%). Six (14.3%) patients experienced grade 3 adverse events. The most common were white blood cell count decrease (31.0%), alopecia (81.0%), asthenia (38.1%), and reactive cutaneous capillary endothelial proliferation (35.7%). 41 patients received minimally invasive oesophagectomy; all 41patients achieved R0 resection, and 18 (43.9%, 95% CI, 28.5-60.3%) patients achieved PCR. The median follow-up was 23 months and the 2-year survival rate was 85.9%. T-cell subsets in both the PCR and NPCR groups exhibited consistency in response to neoadjuvant therapy. In contrast, some of natural killer (NK) cells (NK-C03, NK-C11), B cells (B-C06) and monocytes (M-C05), exhibited significant differences between the PCR and NPCR groups before neoadjuvant therapy. M-C06 had a significant difference in the PCR group and NPCR group after neoadjuvant therapy. NK-C12 and B-C15 showed significant differences both before and after neoadjuvant therapy. Interpretation: The application of camrelizumab, chemotherapy and apatinib in the neoadjuvant setting for locally advanced ESCC has shown promising antitumour activity and an acceptable safety profile in this single-arm study. In the neoadjuvant setting, NK cell, B cell, and monocyte subsets exhibited greater predictive power for immunotherapy responsiveness than T-cell subsets. Longer follow-up to assess survival outcomes and a phase 3 randomised trial are needed to further evaluate the proposed treatment. Funding: The China Anti-Cancer Association and the "Leading Goose" Research and Development Project of Zhejiang Province.

Brimonidine as a possible treatment for myopia.

BACKGROUND: Myopia is becoming a huge burden on the world's public health systems. The purpose of this study was to explore the effect of brimonidine in the treatment of form-deprivation myopia (FDM) and the relationship between intraocular pressure (IOP) and myopia development. METHODS: Monocular form deprivation myopia (FDM) was induced in three-week-old pigmented male guinea pigs. They were treated with 3 different methods of brimonidine administration (eye drops, and subconjunctival or intravitreal injections). Four different concentrations of brimonidine were tested for each method (2µg/µL, 4µg/µL, 20µg/µL, and 40µg/µL). All treatments continued for a period of 21 days. Tonometry, retinoscopy, and A-scan ultrasonography were used to monitor intraocular pressure, refractive error and axial length (AL), respectively. RESULTS: Treatment with subconjunctival brimonidine at 40µg/µL, and intravitreal brimonidine at 2µg/µL and 4µg/µL, inhibited the development of FDM. The myopic refraction, excessive axial length, and elevation of IOP were significantly decreased. Brimonidine in eye drops was ineffective. CONCLUSION: Brimonidine at appropriate doses significantly reduced the development of FD myopia in guinea pigs. The IOP may change with FD myopia.

Repetitive transcranial magnetic stimulation for Alzheimer's disease: an overview of systematic reviews and meta-analysis.

Objective: Alzheimer's disease (AD) is a prevalent neurodegenerative condition that significantly impacts both individuals and society. This study aims to evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) as a treatment for AD by summarizing the evidence from systematic reviews (SRs) and meta-analyses (MAs). Methods: SRs/MAs of rTMS for AD were collected by searching Embase, Web of Science, Cochrane Library, PubMed, CNKI, VIP, Sino-Med, and Wanfang databases. The search was conducted from database creation to January 23, 2024. Methodological quality, reporting quality and risk of bias were assessed using the Assessing Methodological Quality of Systematic Reviews 2 (AMSTAR-2), Risk of Bias in Systematic Reviews (ROBIS) tool and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). In addition, the quality of evidence for outcome measures was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Results: Eight SRs/MAs included in this study met the inclusion criteria. Based on the AMSTAR-2, 4 of the SRs/MA were classified as low quality, while the remaining 4 were deemed to be of very low quality. The PRISMA analysis revealed that out of the 27 items reporting, 16 achieved full reporting (100%). However, there were still some deficiencies in reporting, particularly related to protocol and registration, search strategy, risk of bias, and additional analysis. The ROBIS tool indicated that only 3 SRs/MAs had a low risk of bias. The GRADE assessment indicated that 6 outcomes were of moderate quality (18.75%), 16 were of low quality (50%), and 10 were classified as very low quality (31.25%). Conclusion: Based on the evidence collected, rTMS appears to be effective in improving cognitive function in AD patients, although the methodological quality of the SRs/MAs reduces the reliability of the conclusions and the overall quality is low. However, based on the available results, we still support the value of rTMS as an intervention to improve cognitive function in AD. In future studies, it is necessary to confirm the efficacy of rTMS in AD patients and provide more reliable and scientific data to contribute to evidence-based medicine.

Boosting Photothermocatalytic Oxidation of Toluene Over Pt/N-TiO2: The Gear Effect of Light and Heat.

Photothermal catalysis is extremely promising for the removal of various indoor pollutants owing to its photothermal synergistic effect, while the low light utilization efficiency and unclear catalytic synergistic mechanism hinder its practical applications. Here, nitrogen atoms are introduced, and Pt nanoparticles are loaded on TiO2 to construct Pt/N-TiO2-H2, which exhibits 3.5-fold higher toluene conversion rate than the pure TiO2. Compared to both photocatalytic and thermocatalytic processes, Pt/N-TiO2-H2 exhibited remarkable performance and stability in the photothermocatalytic oxidation of toluene, achieving 98.4% conversion and 98.3% CO2 yield under a light intensity of 260 mW cm-2. Furthermore, Pt/N-TiO2-H2 demonstrated potential practical applicability in the photothermocatalytic elimination of various indoor volatile organic compounds. The synergistic effect occurs as thermocatalysis accelerates the accumulation of carboxylate species and the degradation of aldehyde species, while photocatalysis promotes the generation of aldehyde species and the consumption of carboxylate species. This ultimately enhances the photothermocatalytic process. The photothermal synergistic effect involves the specific conversion of intermediates through the interplay of light and heat, providing novel insights for the design of photothermocatalytic materials and the understanding of photothermal mechanisms.

Rapamycin vs TORin-1 or Gleevec vs Nilotinib: Simple chemical evolution that converts PAK1-blockers to TOR-blockers or vice versa?

Both PAK1 (RAC/CDC42-activating kinase 1) and TOR (Target of Rapamycin) are among the major oncogenic/ageing kinases. However, they play the opposite role in our immune system, namely immune system is suppressed by PAK1, while it requires TOR. Thus, PAK1-blockers, would be more effective for therapy of cancers, than TOR-blockers. Since 2015 when we discovered genetically that PDGF-induced melanogenesis depends on "PAK1", we are able to screening a series of PAK1-blockers as melanogenesis-inhibitors which could eventually promote longevity. Interestingly, rapamycin, the first TOR-inhibitor, promotes melanogenesis, clearly indicating that TOR suppresses melanogenesis. However, a new TOR-inhibitor called TORin-1 no longer suppresses immune system, and blocks melanogenesis in cell culture. These observations strongly indicate that TORin-1 acts as PAK1-blockers, instead of TOR-blockers, in vivo. Thus, it is most likely that melanogenesis in cell culture could enable us to discriminate PAK1-blockers from TORblockers.

Two IFNa3s mediate the regulation of IRF9 in the process of infection with Streptococcus iniae in yellowfin seabream, Acanthopagrus latus (Hottuyn, 1782).

IRF9 can play an antibacterial role by regulating the type I interferon (IFN) pathway. Streptococcus iniae can cause many deaths of yellowfin seabream, Acanthopagrus latus in pond farming. Nevertheless, the regulatory mechanism of type I IFN signalling by A. latus IRF9 (AlIRF9) against S. iniae remains elucidated. In our study, AlIRF9 has a total cDNA length of 3200 bp and contains a 1311 bp ORF encoding a presumed 436 amino acids (aa). The genomic DNA sequence of AlIRF9 has nine exons and eight introns, and AlIRF9 was expressed in various tissues, containing the stomach, spleen, brain, skin, and liver, among which the highest expression was in the spleen. Moreover, AlIRF9 transcriptions in the spleen, liver, kidney, and brain were increased by S. iniae infection. By overexpression of AlIRF9, AlIRF9 is shown as a whole-cell distribution, mainly concentrated in the nucleus. Moreover, the promoter fragments of -415 to +192 bp and -311 to +196 bp were regarded as core sequences from two AlIFNa3s. The point mutation analyses verified that AlIFNa3 and AlIFNa3-like transcriptions are dependent on both M3 sites with AlIRF9. In addition, AlIRF9 could greatly reduce two AlIFNa3s and interferon signalling factors expressions. These results showed that in A. latus, both AlIFNa3 and AlIFNa3-like can mediate the regulation of AlIRF9 in the process of infection with S. iniae.

Expert consensus on pediatric orthodontic therapies of malocclusions in children.

Malocclusion, identified by the World Health Organization (WHO) as one of three major oral diseases, profoundly impacts the dental-maxillofacial functions, facial esthetics, and long-term development of ~260 million children in China. Beyond its physical manifestations, malocclusion also significantly influences the psycho-social well-being of these children. Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition, by mitigating the negative impact of abnormal environmental influences on the growth. Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development, ranging from fetal stages to the early permanent dentition phase. From an economic and societal standpoint, the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated, underlining its profound practical and social importance. This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children, emphasizing critical need for early treatment. It elaborates on corresponding core principles and fundamental approaches in early orthodontics, proposing comprehensive guidance for preventive and interceptive orthodontic treatment, serving as a reference for clinicians engaged in early orthodontic treatment.

Functional therapy and adenotonsillectomy clinical trial for class II malocclusion (FACT-II): protocol for a randomised controlled trial.

INTRODUCTION: Class II malocclusion with mandibular retrognathia is a common complication of paediatric obstructive sleep apnoea (OSA), often accompanied by transverse maxillary deficiency. In early orthodontic treatment, a twin block (TB) is a regular functional appliance for correcting this malocclusion. For paediatric OSA, the most common risk factor is adenotonsillar hypertrophy (AHT). Untreated AHT may lead to the persistence and worsening of obstructive sleep-disordered breathing traits, including habitual mouth breathing. Additionally, the clockwise mandibular rotation associated with AHT-induced pharyngeal crowding can undermine the effectiveness and stability of TB treatment. Adenotonsillectomy (T&A) is currently the first-line treatment for paediatric OSA. This proposed trial will investigate the impact of T&A surgery timing on the efficacy and stability of TB functional treatment in children with class II mandibular retrognathia and ATH. METHODS AND ANALYSIS: This will be a single-centre, parallel-group, superiority randomised controlled trial with participants randomised to intervention (T&A followed by TB treatment) or control arms (TB treatment followed by T&A) in a 1:1 ratio. A total of 40 patients aged 8-14 years, diagnosed with class II mandibular retrognathia and co-existing ATH-induced OSA, and indicated for both T&A surgery and TB treatment, will be recruited at the School and Hospital of Stomatology, Wuhan University. The primary outcomes will be the changes in the apnoea-hypopnoea index and the point A-nasion-point B angle from baseline to postorthodontic treatment between the two groups. Secondary outcomes will include other dental, skeletal, upper airway and soft tissue changes, as well as subjective sleep-related and oral-related quality of life. Outcome changes within each group and between groups will be analysed. ETHICS AND DISSEMINATION: This study is approved by the Ethics Committee of the School and Hospital of Stomatology, Wuhan University (no. 2022-D07). The research findings will be faithfully disseminated through scientific conferences or published articles. TRIAL REGISTRATION NUMBER: ChiCTR2200061703 (https://www.chictr.org.cn).

High keratin 15 expression reflects favorable prognosis in early cervical cancer patients.

OBJECTIVE: Keratin 15 (KRT15) exhibits inconsistent prognostic roles in different cancers, and its prognostic value in early cervical cancer patients who receive tumor resection remains unknown. This study aimed to assess the relationship of KRT15 expression with prognosis in these patients. METHODS: Totally, 147 early cervical cancer patients who received tumor resection were reviewed in this retrospective study. KRT15 was detected in formalin-fixed paraffin-embedded tumor tissue by immunohistochemistry (IHC). KRT15 IHC scores were computed by multiplying the percentage of positively stained cells (scored as 0-4) and corresponding staining intensity (scored as 0-3), ranging from 0 to 12. RESULTS: Elevated KRT15 IHC score was linked with moderate to well differentiation (P = 0.005), tumor size ≤ 4 cm (P = 0.017), and International Federation of Gynecology and Obstetrics (FIGO) stage Ia/Ib (P < 0.001). KRT15 IHC score was inversely associated with adjuvant radiotherapy (P = 0.025) and adjuvant chemotherapy (P = 0.016). KRT15 IHC score ≥ 1 was linked with increased disease-free survival (DFS) (P = 0.003) and overall survival (OS) (P = 0.049). Meanwhile, KRT15 IHC score ≥ 1 independently predicted increased DFS (hazard ratio = 0.213, P = 0.017), but not OS (P > 0.05). KRT15 IHC score ≥ 3 and KRT15 IHC score ≥ 6 could not predict DFS or OS (all P > 0.05). By subgroup analyses, KRT15 IHC score ≥ 1 forecasted favorable DFS in patients with age > 45 years, human papillomavirus-positive, squamous carcinoma, and tumor size ≤ 4 cm (all P < 0.05). KRT15 IHC score ≥ 1 and KRT15 IHC score ≥ 3 predicted ascended DFS in patients without adjuvant radiotherapy or adjuvant chemotherapy (all P < 0.05). CONCLUSION: High KRT15 expression reflects favorable tumor features and longer survival in early cervical cancer patients who receive tumor resection.

Enterococcus faecalis provides protection during scavenging in carrion crow ( Corvus corone).

The gut microbiota significantly influences host physiology and provides essential ecosystem services. While diet can affect the composition of the gut microbiota, the gut microbiota can also help the host adapt to specific dietary habits. The carrion crow ( Corvus corone), an urban facultative scavenger bird, hosts an abundance of pathogens due to its scavenging behavior. Despite this, carrion crows infrequently exhibit illness, a phenomenon related to their unique physiological adaptability. At present, however, the role of the gut microbiota remains incompletely understood. In this study, we performed a comparative analysis using 16S rRNA amplicon sequencing technology to assess colonic content in carrion crows and 16 other bird species with different diets in Beijing, China. Our findings revealed that the dominant gut microbiota in carrion crows was primarily composed of Proteobacteria (75.51%) and Firmicutes (22.37%). Significant differences were observed in the relative abundance of Enterococcus faecalis among groups, highlighting its potential as a biomarker of facultative scavenging behavior in carrion crows. Subsequently, E. faecalis isolated from carrion crows was transplanted into model mice to explore the protective effects of this bacterial community against Salmonella enterica infection. Results showed that E. faecalis down-regulated the expression of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and interleukin 6 (IL-6), prevented S. enterica colonization, and regulated the composition of gut microbiota in mice, thereby modulating the host's immune regulatory capacity. Therefore, E. faecalis exerts immunoregulatory and anti-pathogenic functions in carrion crows engaged in scavenging behavior, offering a representative case of how the gut microbiota contributes to the protection of hosts with specialized diets.

Spatial Distribution of Brønsted Acid Sites Determines the Mobility of Reactive Cu Ions in the Cu-SSZ-13 Catalyst during the Selective Catalytic Reduction of NOx with NH3.

The formation of dimer-Cu species, which serve as the active sites of the low-temperature selective catalytic reduction of NOx with NH3 (NH3-SCR), relies on the mobility of CuI species in the channels of the Cu-SSZ-13 catalysts. Herein, the key role of framework Brønsted acid sites in the mobility of reactive Cu ions was elucidated via a combination of density functional theory calculations, in situ impedance spectroscopy, and in situ diffuse reflectance ultraviolet-visible spectroscopy. When the number of framework Al sites decreases, the Brønsted acid sites decrease, leading to a systematic increase in the diffusion barrier for [Cu(NH3)2]+ and less formation of highly reactive dimer-Cu species, which inhibits the low-temperature NH3-SCR reactivity and vice versa. When the spatial distribution of Al sites is uneven, the [Cu(NH3)2]+ complexes tend to migrate from an Al-poor cage to an Al-rich cage (e.g., cage with paired Al sites), which effectively accelerates the formation of dimer-Cu species and hence promotes the SCR reaction. These findings unveil the mechanism by which framework Brønsted acid sites influence the intercage diffusion and reactivity of [Cu(NH3)2]+ complexes in Cu-SSZ-13 catalysts and provide new insights for the development of zeolite-based catalysts with excellent SCR activity by regulating the microscopic spatial distribution of framework Brønsted acid sites.

Four new tirucallane-type triterpenoids from Aphanamixis polystachya.

Four new tirucallane-type triterpenoids, polystanins H-K (1-4), were obtained from the stems and leaves of Aphanamixis polystachya. Their structures were elucidated by analysis of the spectroscopic data and comparison with literature data. Compounds 1 and 2 showed week inhibitory effects against NO production in LPS-stimulated RAW264.7 cells. All the isolates were investigated for their antifungal activities against drug-resistant Candida albicans.

[Pathogenic mechanisms of impaired neuronal autophagy flux after ischemic stroke].

Autophagy is a metabolic process in which damaged organelles, obsolete proteins, excess cytoplasmic components, and even pathogens are presented to lysosomes for degradation via autophagosomes. It includes 4 processes: the initiation of autophagy, the formation of autophagosomes, the fusion of autophagosomes with lysosomes, and the degradation and removal of autophagic substrates within autophagic lysosomes. When these processes are continuous, it is called autophagy flux. Blockage of one or certain steps in the autophagy/lysosome signaling pathway can lead to impaired autophagy flux. Numerous studies have shown that impaired autophagy flux is an important cause of neuronal damage in the ischemic penumbra after stroke. This paper summarized research progress in the pathological mechanisms that cause impaired neuronal autophagy flux after ischemic stroke and discusses methods to improve neuronal autophagy flux, in order to provide a reference for an in-depth investigation of the pathological injury mechanisms after stroke.

The effect of social pension on health-related quality of life of the rural older people: a panel study from China.

BACKGROUND: Social pensions, social assistance systems for older people in rural areas, have been put into place in many nations and have positively impacted health. The long-term health consequences of social pension programs in China are uncertain. The aim of this study is to evaluate the long-term health consequences of the new rural social pension (NRSP) for the rural older people in China. METHODS: Based on the 2011 and 2018 China Health and Retirement Longitudinal Study, we compared the scores on eight Health-Related Quality of Life (HRQoL) subscales of the rural older people before and after participation in the NRSP. The propensity score matching and difference-in-difference methods were used in data analysis. We also conducted a heterogeneity analysis for subgroups with different characteristics and pension enrolment times. RESULTS: The NRSP significantly enhanced scores on physical functioning, role-physical, and self-rated mental health of old rural participants by 1.90 (p < 0.01), 2.05 (p < 0.01), and 2.93 (p < 0.05), respectively. After excluding newly enrolled individuals, the beneficial health effects of the NRSP remained significant. There were no significant changes due to NRSP in the other five scores on the HRQoL subscale of the rural older people. The NRSP had more health benefits for older people in underdeveloped areas without formal schooling. CONCLUSIONS: The NRSP reduced health disparities and had long-term benefits on the physical and mental health of the rural older people. We suggest continuously expanding the NRSP throughout rural China and further improving the social support system to enhance the overall quality of life of the rural older people. Comparable social pension programs aimed at underprivileged groups could also be conducted in other low- or middle-income nations.

The Relationship between Concentration Effort, Focus Back Effort, Focus Back State, and Mind Wandering.

Focus back effort, concentration effort, and focus back state are factors associated with mind wandering. Focus back effort, proposed in alignment with the definition of focus back state, has been previously regarded as one manifestation of concentration effort. The primary goals of the current study are to explore the relationship between concentration effort, focus back effort, focus back state, and mind wandering. To shed light on the issue, we assessed the level of each cognitive measure in a single task. The findings revealed significant correlations between concentration effort, focus back effort, focus back state, and mind wandering. Mediation analysis suggested that focus back effort played a mediating role in the relationship between concentration effort and focus back state. Additionally, we observed that these measures independently influenced task performance through their impact on mind wandering. Our results provide potential avenues for interventions aimed at addressing individuals' mind wandering and enhancing task performance.

Interchain-expanded extra-large-pore zeolites.

Stable aluminosilicate zeolites with extra-large pores that are open through rings of more than 12 tetrahedra could be used to process molecules larger than those currently manageable in zeolite materials. However, until very recently1-3, they proved elusive. In analogy to the interlayer expansion of layered zeolite precursors4,5, we report a strategy that yields thermally and hydrothermally stable silicates by expansion of a one-dimensional silicate chain with an intercalated silylating agent that separates and connects the chains. As a result, zeolites with extra-large pores delimited by 20, 16 and 16 Si tetrahedra along the three crystallographic directions are obtained. The as-made interchain-expanded zeolite contains dangling Si-CH3 groups that, by calcination, connect to each other, resulting in a true, fully connected (except possible defects) three-dimensional zeolite framework with a very low density. Additionally, it features triple four-ring units not seen before in any type of zeolite. The silicate expansion-condensation approach we report may be amenable to further extra-large-pore zeolite formation. Ti can be introduced in this zeolite, leading to a catalyst that is active in liquid-phase alkene oxidations involving bulky molecules, which shows promise in the industrially relevant clean production of propylene oxide using cumene hydroperoxide as an oxidant.

[Determination of three new herbicide residues in soil, sediment and water by liquid chromatography-tandem mass spectrometry].

Herbicides play an important role in preventing and controlling weeds and harmful plants and are increasingly used in agriculture, forestry, landscaping, and other fields. However, the effective utilization rate of herbicides is only 20%-30%, and most herbicides enter the atmosphere, soil, sediment, and water environments through drift, leaching, and runoff after field application. Herbicide residues in the environment pose potential risks to ecological safety and human health. Therefore, establishing analytical methods to determine herbicide residues in environmental samples is of great importance. In this study, an analytical method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) in positive electrospray ionization mode (ESI+) was developed for the determination of isoxaflutole, metazachlor, and saflufenacil residues in soil, sediment, and water. The instrumental detection parameters, including electrospray ionization mode, mobile phase, and chromatographic column, were optimized. The mobile phases were methanol (A) and 0.1% formic acid aqueous solution (B). Gradient elution was performed as follows: 0-1.0 min, 60%A; 1.0-2.0 min, 60%A-90%A; 2.0-3.0 min, 90%A; 3.0-4.0 min, 90%A-60%A; 4.0-5.0 min, 60%A. The samples were salted after extraction with acetonitrile and cleaned using a C18 solid-phase extraction column. Different solid-phase extraction columns and leaching conditions were investigated during sample pretreatment. Working curves in the neat solvent and matrix were constructed by plotting the measured peak areas as a function of the concentrations of the analytes in the neat solvent and matrix. Good linearities were found for isoxaflutole, metazachlor, and saflufenacil in the solvent and matrix-matched standards in the range of 0.0005-0.02 mg/L, with r≥0.9961. The matrix effects of the three herbicides in soil, sediment, and water ranged from -10.1% to 16.5%. The limits of detection (LODs, S/N=3) for isoxaflutole, metazachlor, and saflufenacil were 0.05, 0.01, and 0.02 µg/kg, respectively. The limits of quantification (LOQs, S/N=10) for isoxaflutole, metazachlor, and saflufenacil were 0.2, 0.05, and 0.05 µg/kg, respectively. The herbicides were applied to soil, sediment, and water at spiked levels of 0.005, 0.1, and 2.0 mg/kg, respectively. The average recoveries for isoxaflutole, metazachlor, and saflufenacil in soil, sediment, and water were in the ranges of 77.2%-101.9%, 77.9%-105.1%, and 80.8%-107.1%, respectively. The RSDs for isoxaflutole, metazachlor, and saflufenacil were in the ranges of 1.4%-12.8%, 1.2%-7.7%, and 1.5%-11.5%, respectively. The established method was used to analyze actual samples collected from four different sites in Zhejiang Province (Xiaoshan, Taizhou, Dongyang, and Yuhang) and one site in Heilongjiang (Jiamusi). The proposed method is simple, rapid, accurate, stable, and highly practical. It can be used to detect isoxaflutole, metazachlor, and saflufenacil residues in soil, sediment, and water and provides a reference for monitoring the residual pollution and environmental behavior of herbicides.

Hu8F4-CAR T cells with mutated Fc spacer segment improve target-specificity and mediate anti-leukemia activity in vivo.

Hu8F4 is a T cell receptor (TCR)-like antibody with high affinity for leukemia-associated antigen PR1/HLA-A2 epitope. Adapted into a chimeric antigen receptor (CAR) format, Hu8F4-CAR is comprised of the Hu8F4 scFv, the human IgG1 CH2CH3 extracellular spacer domain, a human CD28 costimulatory domain, and the human CD3ζ signaling domain. We have demonstrated high efficacy of Hu8F4-CAR-T cells against PR1/HLA-A2-expressing cell lines and leukemic blasts from AML patients in vitro. Previous studies have shown that modification of the Fc domains of IgG4 CH2CH3 spacer regions can eliminate activation-induced cell death and off-target killing mediated by mouse Fc gamma receptor (FcgR)-expressing cells. We generated Hu8F4-CAR(PQ) with mutated Fc receptor binding sites on the CH2 domain of Hu8F4-CAR to prevent unwanted interactions with FcgR-expressing cells in vivo. The primary human T cells transduced with Hu8F4-CAR(PQ) can specifically lyse HLA-A2+ PR1-expressing leukemia cell lines in vitro. Furthermore, both adult donor-derived and cord blood-derived Hu8F4-CAR(PQ)-T cells are active and can eliminate U937 leukemia cells in NSG mice. Herein, we demonstrate that modification of the IgG1-based spacer can eliminate Fc receptor-binding-induced adverse effects and Hu8F4-CAR(PQ)-T cells can kill leukemia in vivo.

CURRENT NEURAL NETWORKS DEMONSTRATE POTENTIAL IN AUTOMATED CERVICAL VERTEBRAL MATURATION STAGE CLASSIFICATION BASED ON LATERAL CEPHALOGRAMS.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Neural networks for classification of cervical vertebrae maturation: a systematic review. Mathew R, Palatinus S, Padala S, Alshehri A, Awadh W, Bhandi S, Thomas J, Patil S. Angle Orthod. 2022 Nov 1;92(6):796-804. SOURCE OF FUNDING: No financial support was reported. TYPE OF STUDY/DESIGN: Systematic review.

Combined Experimental and Density Functional Theory Study on the Mechanism of the Selective Catalytic Reduction of NO with NH3 over Metal-Free Carbon-Based Catalysts.

Metal-free carbon-based catalysts are attracting much attention in the low-temperature selective catalytic reduction of NOx with NH3 (NH3-SCR). However, the mechanism of the NH3-SCR reaction on carbon-based catalysts is still controversial, which severely limits the development of carbon-based SCR catalysts. Herein, we successfully reconstructed carbon-based catalysts through oxidation treatment with nitric acid, thereby enhancing their low-temperature activity in NH3-SCR. Combining experimental results and density functional theory (DFT) calculations, we proposed a previously unreported NH3-SCR reaction mechanism over carbon-based catalysts. We demonstrated that C-OH and C-O-C groups not only effectively activate NH3 but also remarkedly promote the decomposition of intermediate NH2NO. This study enhances the understanding of the NH3-SCR mechanism on carbon-based catalysts and paves the way to develop low-temperature metal-free SCR catalysts.