Predictive modeling for postoperative delirium in elderly patients with abdominal malignancies using synthetic minority oversampling technique.

BACKGROUND: Postoperative delirium, particularly prevalent in elderly patients after abdominal cancer surgery, presents significant challenges in clinical management. AIM: To develop a synthetic minority oversampling technique (SMOTE)-based model for predicting postoperative delirium in elderly abdominal cancer patients. METHODS: In this retrospective cohort study, we analyzed data from 611 elderly patients who underwent abdominal malignant tumor surgery at our hospital between September 2020 and October 2022. The incidence of postoperative delirium was recorded for 7 d post-surgery. Patients were divided into delirium and non-delirium groups based on the occurrence of postoperative delirium or not. A multivariate logistic regression model was used to identify risk factors and develop a predictive model for postoperative delirium. The SMOTE technique was applied to enhance the model by oversampling the delirium cases. The model's predictive accuracy was then validated. RESULTS: In our study involving 611 elderly patients with abdominal malignant tumors, multivariate logistic regression analysis identified significant risk factors for postoperative delirium. These included the Charlson comorbidity index, American Society of Anesthesiologists classification, history of cerebrovascular disease, surgical duration, perioperative blood transfusion, and postoperative pain score. The incidence rate of postoperative delirium in our study was 22.91%. The original predictive model (P1) exhibited an area under the receiver operating characteristic curve of 0.862. In comparison, the SMOTE-based logistic early warning model (P2), which utilized the SMOTE oversampling algorithm, showed a slightly lower but comparable area under the curve of 0.856, suggesting no significant difference in performance between the two predictive approaches. CONCLUSION: This study confirms that the SMOTE-enhanced predictive model for postoperative delirium in elderly abdominal tumor patients shows performance equivalent to that of traditional methods, effectively addressing data imbalance.

Treatment strategies and molecular mechanism of radiotherapy combined with immunotherapy in colorectal cancer.

Radiotherapy (RT) remodels the tumor immune microenvironment (TIME) and modulates the immune response to indirectly destroy tumor cells, in addition to directly killing tumor cells. RT combined with immunotherapy may significantly enhance the efficacy of RT in colorectal cancer by modulating the microenvironment. However, the molecular mechanisms by which RT acts as an immunomodulator to modulate the immune microenvironment remain unclear. Further, the optimal modalities of RT combined with immunotherapy for the treatment of colorectal cancer, such as the time point of combining RT and immunization, the fractionation pattern and dosage of radiotherapy, and other methods to improve the efficacy, are also being explored parallelly. To address these aspects, in this review, we summarized the mechanisms by which RT modulates TIME and concluded the progress of RT combined with immunization in preclinical and clinical trials. Finally, we discussed heavy ion radiation therapy and the efficacy of prediction markers and other immune combination therapies. Overall, combining RT with immunotherapy to enhance antitumor effects will have a significant clinical implication and will help to facilitate individualized treatment modalities.

Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury.

BACKGROUND: Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances. However, its contribution to the progression of liver damage remains unclear. AIM: To determine the role and mechanism of UGT1A1 in liver damage progression. METHODS: We investigated the relationship between UGT1A1 expression and liver injury through clinical research. Additionally, the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model study. RESULTS: Patients with UGT1A1 gene mutations showed varying degrees of liver damage, while patients with acute-on-chronic liver failure (ACLF) exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic hepatitis. This suggests that low UGT1A1 levels may be associated with the progression of liver damage. In mouse models of liver injury induced by carbon tetrachloride (CCl4) and concanavalin A (ConA), the hepatic levels of UGT1A1 protein were found to be increased. In mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression, the hepatic protein levels of UGT1A1 were decreased, which is consistent with the observations in patients with ACLF. UGT1A1 knockout exacerbated CCl4- and ConA-induced liver injury, hepatocyte apoptosis and necroptosis in mice, intensified hepatocyte endoplasmic reticulum (ER) stress and oxidative stress, and disrupted lipid metabolism. CONCLUSION: UGT1A1 is upregulated as a compensatory response during liver injury, and interference with this upregulation process may worsen liver injury. UGT1A1 reduces ER stress, oxidative stress, and lipid metabolism disorder, thereby mitigating hepatocyte apoptosis and necroptosis.

Examining the Antecedents of Novice STEM Teachers' Job Satisfaction: The Roles of Personality Traits, Perceived Social Support, and Work Engagement.

It is reported that teachers' satisfaction levels are lower and stress levels are higher than other professional groups in many countries. This is especially true for science, technology, engineering, and mathematics (STEM) teachers. Considering job satisfaction has a direct impact on turnover intention, low satisfaction levels have led to high turnover rates and thus exacerbated the shortages of STEM teachers. Hence, there is an urgent need to explore the antecedents of novice STEM teachers' job satisfaction. This study proposes a new model to show how novice STEM teachers' personality traits and perceived social support influence their job satisfaction. A total of 2592 novice STEM teachers in eighteen randomly selected high schools in China were recruited. Data were analyzed using the structural equation modeling approach. The results illustrated that most novice STEM teachers had low levels of job satisfaction. Novice STEM teachers' personality traits could directly and indirectly impact their job satisfaction. Meanwhile, novice STEM teachers' job satisfaction was also directly influenced by work engagement and indirectly influenced by their perceived social support. Our findings theoretically contribute to the understanding of the determinants of STEM teachers' job satisfaction and have important practical implications.

Enhancing Women's Quality of Life: Exploring the Impact of Mastectomy with and without Breast Reconstruction among Breast Cancer Survivors in Iraq.

BACKGROUND AND AIMS: Mastectomy, a common intervention for breast cancer, has substantial implications for a woman's quality of life (QoL). However, the literature on QoL outcomes following mastectomy-with or without breast reconstruction (BR) is scant. This study aims to assess and compare the QoL among Iraqi women post-mastectomy, examining the impacts of undergoing BR. METHODS: We conducted a comprehensive cross-sectional study across multiple centers in Iraq from April to September 2021. Our cohort consisted of 404 women who had a mastectomy for breast cancer treatment, 154 of whom also chose to have BR. Utilizing the European Organisation for Research and Treatment of Cancer's (EORTC) tools specifically, select domains from EORTC QLQ-BR23, QLQ-C30, and QLQ-BRECON23-we evaluated various facets of their QoL. RESULTS: The mean QoL score was 54 out of 100, with patients who did not undergo BR reporting slightly higher scores (55) compared to those who did (52). Notably, social and sexual functioning scores were statistically superior in the non-BR group. Satisfaction with surgery, sexual function, and breast aesthetics were the lowest rated aspects among BR patients, indicating a considerable gap between expectations and outcomes. Marital status and the type of mastectomy notably influenced body image and sexual function. A significant portion of patients (100 out of 250) opted out of BR due to recurrence concerns, while 26.2% (106 out of 154) pursued BR to restore their pre-mastectomy physique. CONCLUSION: Contrary to the anticipated benefits of BR, our findings suggest that women who underwent the procedure reported a lower QoL compared to those who did not. The outcomes highlight the discrepancy between expected and actual benefits of BR, suggesting a pressing need for comprehensive rehabilitation programs. These programs should aim to enhance the QoL for post-mastectomy patients and provide in-depth counseling to align expectations with the potential realities of BR.

Lactobacillus reuteri's multifaceted role in mitigating ionizing radiation-induced injury in Drosophila melanogaster.

The numerous beneficial probiotic properties of Lactobacillus reuteri (L. reuteri) include decreasing metabolic syndrome, preventing disorders linked to oxidative stress, improving gut flora imbalances, controlling immunological function, and extending life span. Exposure to ionizing radiation is closely associated with several disorders. We examined the protective and salvaging effects of L. reuteri on ionizing radiation-induced injury to the intestinal tract, reproductive system, and nervous system of Drosophila melanogaster. We also examined its effects on lifespan, antioxidant capacity, progeny development, and behavioral aspects to assess the interaction between L. reuteri and ionizing radiation-induced injury. The findings demonstrated that L. reuteri improved the median survival time following irradiation and greatly extended its lifespan. In addition, it raised SOD activity, reduced ROS levels in intestinal epithelial cells, and increased the quantity of intestinal stem cells. Furthermore, L. reuteri enhanced the adult male flies' capacity to move. It also successfully safeguarded the generations' growth and development. L. reuteri dramatically enhanced expression of the AMPKα gene and regulated expression of its pathway-related gene, mTOR, as well as the autophagy-related genes Atg1 and Atg5 in female Drosophila exposed to irradiation. Notably, no prior reports have been made on the possible effects of L. reuteri on injuries caused by irradiation. As a result, our research offers important new information regarding L. reuteri's possible role as a shield against ionizing radiation-induced injury.

[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.

New Insights into the Role of Humic Acid in Permanganate Oxidation of Diclofenac: A Novel Electron Transfer Mechanism.

Humic acid (HA) ubiquitously existing in aquatic environments has been reported to significantly impact permanganate (KMnO4) decontamination processes. However, the underlying mechanism of the KMnO4/HA system remained elusive. In this study, an enhancing effect of HA on the KMnO4 oxidation of diclofenac (DCF) was observed over a wide solution pH range of 5-9. Surprisingly, the mechanism of HA-induced enhancement varied with solution pH. Quenching and chemical probing experiments revealed that manganese intermediates (Mn(III)-HA and MnO2) were responsible for the enhancement under acidic conditions but not under neutral and alkaline conditions. By combining KMnO4 decomposition, galvanic oxidation process experiments, electrochemical tests, and FTIR and XPS analysis, it was interestingly found that HA could effectively mediate the electron transfer from DCF to KMnO4 in neutral and alkaline solutions, which was reported for the first time. The formation of an organic-catalyst complex (i.e., HA-DCF) with lower reduction potential than the parent DCF was proposed to be responsible for the accelerated electron transfer from DCF to KMnO4. This electron transfer likely occurred within the complex molecule formed through the interaction between HA-DCF and KMnO4 (i.e., HA-DCF-KMnO4). These results will help us gain a more comprehensive understanding of the role of HA in the KMnO4 oxidation processes.

Symmetry constraints on the orientation dependence of high-order elastic constants for the hexagonal boron nitride monolayer.

Group theory is a powerful tool to explore fundamental symmetry constraints for the physical properties of crystal structures, e.g. it is well-known that only a few components of the elastic constants are independent due to the symmetry constraint. This work further applies group theory to derive constraint relationships for high-order elastic constants with respect to the orientation angle, where the constraint relationships are more explicit than the traditional tensor transformation law. These analytic symmetry constraints are adopted to explain the molecular dynamics simulation results, which disclose that the high-order elastic constants are highly anisotropic with an anisotropy percentage of up to 25% for the hexagonal boron nitride monolayer. The elastic constant is a basic quantity in the mechanics field, so its high anisotropy shall cause strong anisotropy for other mechanical properties. Based on the anisotropic high-order elastic constants, we demonstrate that Poisson's ratio is highly anisotropic for the hexagonal boron nitride at large strains. These findings provide fundamental insights into the symmetry dependence of high-order elastic constants and other mechanical properties.

Efficacy and safety of drug-coated balloon for de novo lesions of large coronary arteries: Systematic review and meta-analysis of randomized controlled trials.

Background: Drug-coated balloon (DCB) is a novel approach to avoiding stent-related complications and has proven effective for the treatment of in-stent restenosis (ISR) and small vessels. However, its role in the treatment of de novo lesions in large vessels is less settled. Aims: To estimate the efficacy and safety of drug-coated balloon versus stent in the treatment of de novo lesions in large coronary arteries. Methods: We searched the literature until April 2023. We judged the safety of DCB based on major adverse cardiovascular events (MACEs), cardiac death, all-cause mortality, non-fatal myocardial infarction, target lesion revascularization (TLR), and bleeding event; and efficacy according to late lumen loss (LLL), minimum lumen diameter (MLD). We conducted subgroup analyses according to stent type and whether urgent PCI was required. Results: A total of 10 RCTs were included. Overall, LLL (mean difference (MD) = -0.19, 95 % confidence interval (CI): -0.32 to -0.06, P = 0.003) was lower in the DCB group than in the Stent arm. This effect was consistent in subgroup analysis regardless of stent type and disease type. In terms of safety indicators, there were no significant differences between DCB and stent. The subgroup analyses found that safety indicators showed no significant differences between DCB and drug-eluting stent (DES), but TLR was lower in the DCB than in the bare metal stent (BMS). Moreover, in ST-elevation myocardial infarction (STEMI), safety indicators and LLL showed no significant differences between DCB and DES, but MLD in the DCB was smaller. While in patients with excluded STEMI, MACE and TLR was lower in the DCB compared with the overall stent. Conclusions: DCB could be a promising alternative for treating de novo lesions in large coronary arteries with satisfactory efficacy and low risk, superior to BMS and not inferior to DES, with a trend toward lower late lumen loss.

Prenatal diagnosis and appearance of nasal chondromesenchymal hamartoma in a fetus: A case report.

We report a case of fetal nasal chondromesenchymal hamartoma (NCMH) first noted on prenatal ultrasound at 34 weeks. A solid-cystic mass which predominantly hyperechoicgenic and relatively clear margin, was located on the left nasal cavity and pharynx, with anterior extension and moderate blood flow. Further follow-up ultrasound examination depicted an enlargement of the tumor. Fetal magnetic resonance imaging (MRI) showed an inhomogeneous signal lesion involving the ethmoid sinuses, nasal cavity, and pharynx. The infant, delivered via cesarean section at 37 + 5 weeks, required urgent neonatology intervention due to respiratory difficulties. Neonatal MRI and computer tomography were subsequently performed at 1 day after birth. Surgical excision occurred at 7 days, confirming NCMH via histological examination. Awareness of this entity, is essential to avoid potentially harmful therapies, especially in prenatal period. Considered NCMH in diagnosis when fetal nasal masses presenting with predominantly high-level echo, well-defined margins and moderate vascularity.

Prevalence and Site of Concomitant Osteochondral Injuries in Patients With Acute Lateral Patellar Dislocation: A Systematic Review and Meta-analysis.

Background: Osteochondral injuries (OCIs) are common in patients with acute lateral patellar dislocation, which can produce both short- and long-;term adverse effects. However, the pattern of these injuries warrants further analysis, especially in relation to patient age. Purpose: To determine the overall prevalence of concomitant OCIs as well as the prevalence differences based on location and age after acute lateral patellar dislocations. Study Design: Systematic review; Level of evidence, 4. Methods: A comprehensive search of PubMed, Embase, Web of Science, and Cochrane Library was completed from inception to July 20, 2022. All articles reporting the prevalence of OCI were included. The sample characteristics such as age, study design, magnetic resonance imaging diagnostic data, and the number of patients with OCI were extracted. The Methodological Index for Non-Randomized Studies (MINORS) was used for quality assessment. The overall and per-;site injury rates were calculated, and the prevalence was stratified by age-;group (≤16 and >16 years) and compared. Results: The systematic review included 39 studies involving 3354 patients. MINORS scores were 11.94 ± 1.98 and 16 ± 3.46 in the noncomparative and comparative studies, respectively. The overall prevalence of bone bruises and OCI was 89.6% (95% CI, 77.4%-97.7%) and 48.8% (95% CI, 39.0%-58.7%), respectively. In both overall and >16-year-old patients, the lateral femoral condyle (LFC) was the most common site of bone bruise (90.5% [95% CI, 84.0%-95.6%] and 91.5% [95% CI, 84.3%-96.9%], respectively); however, the medial patellar bruise was more common in patients ≤16 years (89.2% [95% CI, 82.9%-94.4%]). Among the pooled sites of OCI, the medial patella accounted for the largest proportion (36.9% [95% CI, 28.0%-46.3%]). OCIs were more common in patients >16 years (52.6% [95% CI, 39.4%-65.6%]) than in patients ≤16 years (46.6% [95% CI, 33.2%-60.3%]). Conclusion: Bone bruises on the LFC were most prevalent overall and in patients >16 years, whereas bone bruises on the medial patella were more prevalent in patients ≤16 years. OCIs were frequently seen in patients >16 years, with the most common site being the medial patella.

Use of chalazion clamp for excision of the eyelid margin lesion.

PURPOSE: Reconstruction after eyelid lesion excision is very important. It calls for preserving normal eyelid function for the protection of the eye and restoring good cosmesis. It is important to precisely align the tarsal plate. However, the unique anatomy of eyelids often makes haemostasis difficult and surgical field obscured. We report an effective method to solve this problem. METHOD: This retrospective study included 25 patients who underwent eyelid margin lesion excision using the chalazion clamp between March 2020 and October 2021. The chalazion clamp is placed on the desired location and tightened, providing a bloodless field for eyelid lesion removal. Without bleeding, visibility of the cut edges is improved considerably. It facilitates anatomical anastomosis of the tarsal plate. RESULTS: All 25 patients maintained normal eyelid function and good cosmesis, with no recurrence during the follow-up period. CONCLUSION: The use of the chalazion clamp during excision of the eyelid margin lesion could stabilize the eyelid, protect the eyeball from accidental injury and, and provide a clear bloodless operative field. It can ensure the neatness of the cut edges and offer better incision alignment for suture. It also avoids wasting too much time on haemostasis, without additional expensive equipment.

The Empathy for Pain Stimuli System (EPSS): Development and preliminary validation.

We present the Empathy for Pain Stimuli System (EPSS): a large-scale database of stimuli for studying people's empathy for pain. The EPSS comprises five sub-databases. First, the Empathy for Limb Pain Picture Database (EPSS-Limb) provides 68 painful and 68 non-painful limb pictures, exhibiting people's limbs in painful and non-painful situations, respectively. Second, the Empathy for Face Pain Picture Database (EPSS-Face) provides 80 painful and 80 non-painful pictures of people's faces being penetrated by a syringe or touched by a Q-tip. Third, the Empathy for Voice Pain Database (EPSS-Voice) provides 30 painful and 30 non-painful voices exhibiting either short vocal cries of pain or neutral interjections. Fourth, the Empathy for Action Pain Video Database (EPSS-Action_Video) provides 239 painful and 239 non-painful videos of whole-body actions. Finally, the Empathy for Action Pain Picture Database (EPSS-Action_Picture) provides 239 painful and 239 non-painful pictures of whole-body actions. To validate the stimuli in the EPSS, participants evaluated the stimuli using four different scales, rating pain intensity, affective valence, arousal, and dominance. The EPSS is available to download for free at https://osf.io/muyah/?view_only=33ecf6c574cc4e2bbbaee775b299c6c1 .

Artificial Intelligence Aids Detection of Rotator Cuff Pathology: A Systematic Review.

PURPOSE: To determine the model performance of artificial intelligence (AI) in detecting rotator cuff pathology using different imaging modalities and to compare capability with physicians in clinical scenarios. METHODS: The review followed the PRISMA guidelines and was registered on PROSPERO. The criteria were as follows: 1) studies on the application of AI in detecting rotator cuff pathology using medical images, and 2) studies on smart devices for assisting in diagnosis were excluded. The following data were extracted and recorded: statistical characteristics, input features, AI algorithms used, sample sizes of training and testing sets, and model performance. The data extracted from the included studies were narratively reviewed. RESULTS: A total of 14 articles, comprising 23,119 patients, met the inclusion and exclusion criteria. The pooled mean age of the patients was 56.7 years, and the female rate was 56.1%. The area under the curve (AUC) of the algorithmic model to detect rotator cuff pathology from ultrasound images, MRI images, and radiographic series ranged from 0.789 to 0.950, 0.844 to 0.943, and 0.820 to 0.830, respectively. Notably, 1 of the studies reported that AI models based on ultrasound images demonstrated a diagnostic performance similar to that of radiologists. Another comparative study demonstrated that AI models using MRI images exhibited greater accuracy and specificity compared to orthopedic surgeons in the diagnosis of rotator cuff pathology, albeit not in sensitivity. CONCLUSIONS: The detection of rotator cuff pathology has been significantly aided by the exceptional performance of AI models. In particular, these models are equally adept as musculoskeletal radiologists in using ultrasound to diagnose rotator cuff pathology. Furthermore, AI models exhibit statistically superior levels of accuracy and specificity when using MRI to diagnose rotator cuff pathology, albeit with no marked difference in sensitivity, in comparison to orthopaedic surgeons. LEVEL OF EVIDENCE: Level III, systematic review of Level III studies.

Flexible nanomechanical bit based on few-layer graphene.

Mechanical computers have gained intense research interest at size scales ranging from nano to macro as they may complement electronic computers operating in extreme environments. While nanoscale mechanical computers may be easier to integrate with traditional electronic components, most current nanomechanical computers are based on volatile resonator systems that require continuous energy input. In this study, we propose a non-volatile nanomechanical bit based on the quasi-stable configurations of few-layer graphene with void defects, and demonstrate its multiple quasi-stable states by deriving an analytic relationship for the void configuration based on a competition between the bending energy and the cohesive energy. Using this nanomechanical bit, typical logic gates are constructed to perform Boolean calculations, including NOT, AND, OR, NAND and NOR gates, and demonstrate reprogrammability between these logic gates. We also study the accuracy and the stability of the nanomechanical bits based on the few-layer graphene. These findings provide a novel approach to realize the nanomechanical computing process.

The synergistic effect of oxidant-peroxide coupling systems for water and wastewater treatments.

With the growing complexity and severity of water pollution, it has become increasingly challenging to effectively remove contaminants or inactivate microorganisms just by traditional chemical oxidants such as O3, chlorine, Fe(VI) and Mn(VII). Up till now, numerous studies have indicated that these oxidants in combination with peroxides (i.e., hydrogen peroxide (H2O2), peroxymonosulfate (PMS), peracetic acid (PAA) and periodate (PI)) exhibited excellent synergistic oxidation. This paper provided a comprehensive review on the combination of aforementioned oxidant-peroxide applied in water and wastewater treatments. From one aspect, the paper thoroughly elucidated the synergy mechanism of each oxidant-peroxide combination in turn. Among these combinations, H2O2 or PMS generally performed as the activator of four traditional oxidants above to accelerate reactive species generation and therein various reaction mechanisms, including electron transfer, O atom abstraction and oxo ligand substitution, were involved. In addition, although neither PAA nor PI was able to directly activate Fe(VI) and Mn(VII), they could act as the stabilizer of intermediate reactive iron/manganese species to improve the latter utilization efficiency. From another aspect, this paper summarized the influence of water quality parameters, such as pH, inorganic ions and natural organic matter (NOM), on the oxidation performance of most combined systems. Finally, this paper highlighted knowledge gaps and identified areas that require further research.

Oxidation of amine-based pharmaceuticals with unactivated peroxymonosulfate: Kinetics, mechanisms, and elimination efficiency of NDMA formation.

Amine-based pharmaceuticals are a significant class of N-nitrosodimethylamine (NDMA) precursors. This study investigated the use of unactivated peroxymonosulfate (PMS) to control amine-based pharmaceuticals and their NDMA formation potential. Kinetic analysis and product identification revealed that sumatriptan and doxylamine primarily underwent reactions at their tertiary amine group, while ranitidine and nizatidine had both tertiary amine and thioether group as reaction sites. The NDMA formation from sumatriptan and doxylamine during post-chloramination was significantly reduced with the abatement of the parent contaminants, while the formation of NDMA remained high even if full abatement of ranitidine and nizatidine was achieved. Product formation kinetics and reference standard tests revealed the great contribution of transformation products to NDMA formation. Ranitidine could be oxidized to sulfoxide-type product ranitidine-SO and N-oxide type product ranitidine-NO. Ranitidine-SO exhibited a high NDMA yield comparable to that of ranitidine (>90%), while ranitidine-NO showed a low NDMA yield (2%). With further oxidation of ranitidine-SO at the tertiary amine group, NDMA formation was reduced by more than 90%. The underlying mechanism for the importance of the tertiary amine group in NDMA formation was demonstrated by quantum chemical calculation. These findings underscore the potential of PMS pre-oxidation on NDMA control.

Brain developmental and cortical connectivity changes in transgenic monkeys carrying the human-specific duplicated gene SRGAP2C.

Human-specific duplicated genes contributed to phenotypic innovations during the origin of our own species, such as an enlarged brain and highly developed cognitive abilities. While prior studies on transgenic mice carrying the human-specific SRGAP2C gene have shown enhanced brain connectivity, the relevance to humans remains unclear due to the significant evolutionary gap between humans and rodents. In this study, to investigate the phenotypic outcome and underlying genetic mechanism of SRGAP2C, we generated transgenic cynomolgus macaques (Macaca fascicularis) carrying the human-specific SRGAP2C gene. Longitudinal MRI imaging revealed delayed brain development with region-specific volume changes, accompanied by altered myelination levels in the temporal and occipital regions. On a cellular level, the transgenic monkeys exhibited increased deep-layer neurons during fetal neurogenesis and delayed synaptic maturation in adolescence. Moreover, transcriptome analysis detected neotenic expression in molecular pathways related to neuron ensheathment, synaptic connections, extracellular matrix and energy metabolism. Cognitively, the transgenic monkeys demonstrated improved motor planning and execution skills. Together, our findings provide new insights into the mechanisms by which the newly evolved gene shapes the unique development and circuitry of the human brain.

Ulk4 promotes Shh signaling by regulating Stk36 ciliary localization and Gli2 phosphorylation.

The Hedgehog (Hh) family of secreted proteins governs embryonic development and adult tissue homeostasis through the Gli family of transcription factors. Gli is thought to be activated at the tip of primary cilium, but the underlying mechanism has remained poorly understood. Here, we show that Unc-51-like kinase 4 (Ulk4), a pseudokinase and a member of the Ulk kinase family, acts in conjunction with another Ulk family member Stk36 to promote Gli2 phosphorylation and Hh pathway activation. Ulk4 interacts with Stk36 through its N-terminal region containing the pseudokinase domain and with Gli2 via its regulatory domain to bridge the kinase and substrate. Although dispensable for Hh-induced Stk36 kinase activation, Ulk4 is essential for Stk36 ciliary tip localization, Gli2 phosphorylation, and activation. In response to Hh, both Ulk4 and Stk36 colocalize with Gli2 at ciliary tip, and Ulk4 and Stk36 depend on each other for their ciliary tip accumulation. We further show that ciliary localization of Ulk4 depends on Stk36 kinase activity and phosphorylation of Ulk4 on Thr1023, and that ciliary tip accumulation of Ulk4 is essential for its function in the Hh pathway. Taken together, our results suggest that Ulk4 regulates Hh signaling by promoting Stk36-mediated Gli2 phosphorylation and activation at ciliary tip.