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Abstract Nickel-catalyzed C–H bond functionalization reactions provide an impressive alternative to those with noble metal catalysts due to their unique reactivity and low cost. However, the regioselective C(sp2)–H borylation reaction of arenes accomplished by nickel catalyst remains limited. We herein disclose a silyl-directed ortho C(sp2)–H borylation of substituted arenes with a Ni(cod)2/PMe3/KHMDS catalyst system. Using readily available starting materials, this protocol provides easy access to ortho-borylated benzylic hydrosilanes bearing flexible substitution patterns. These products can serve as versatile building blocks for the synthesis of sila or sila/borine heterocycles under mild conditions. Control experiments and DFT calculations suggest that a catalytic amount of base prompts the formation of Ni(II)-Bpin-ate complex, likely related to the C(sp2)–H bond activation. This borylation reaction might follow an unusual Ni(II)/Ni(IV) catalytic cycle.

Abstract Based on the perceptions of college student participants in winter and summer, the effects of different vegetation structures within landscapes (single-layer woodland, tree-shrub-grass composite woodlands, tree-grass composite woodland, and single-layer grassland) and concrete squares without plants were investigated, and the skin conductivity level (SCL) and environmental perception recovery score (PRS) associated with landscape types were calculated. The results indicated that seasonal differences in landscape perception significantly affected college student participants' PRS but not their SCL scores, both in winter and summer. Viewing single-layer and tree-shrub-grass composite woodlands in summer, as well as single-layer woodland in winter, enhanced the environmental perception of the college student participants. The restorative effects of the four vegetation types in green spaces were ranked as follows: single-layer woodland, tree-shrub-grass composite woodlands, single-layer grassland, and tree-grass composite woodlands and concrete squares without plants. These findings underscore the importance of considering seasonal variations when choosing plant species for landscaping purposes, with evergreen single-layer woodland being a suitable choice for winter urban landscapes. This provides a scientific basis for assessing landscape perception and preferences in the future.

Abstract The challenge of disease relapsed/refractory (R/R) remains a therapeutic hurdle in chimeric antigen receptor (CAR) T‐cell therapy, especially for hematological diseases, with chronic lymphocytic leukemia (CLL) being particularly resistant to CD19 CAR T cells. Currently, there is no approved CAR T‐cell therapy for CLL patients. In this study, we aimed to address this unmet medical need by choosing the B‐cell activating factor receptor (BAFF‐R) as a promising target for CAR design against CLL. BAFF‐R is essential for B‐cell survival and is consistently expressed on CLL tumors. Our research discovered that BAFF‐R CAR T‐cell therapy exerted the cytotoxic effects on both CLL cell lines and primary B cells derived from CLL patients. In addition, the CAR T cells exhibited cytotoxicity against CD19‐knockout CLL cells that are resistant to CD19 CAR T therapy. Furthermore, we were able to generate BAFF‐R CAR T cells from small blood samples collected from CLL patients and then demonstrated the cytotoxic effects of these patient‐derived CAR T cells against autologous tumor cells. Given these promising results, BAFF‐R CAR T‐cell therapy has the potential to meet the long‐standing need for an effective treatment on CLL patients.

Inspiring the creative potential of overqualified employees can facilitate a mutually beneficial outcome for both the company and the employees. However, further investigation is required to ascertain how to stimulate the perceived overqualification of employees to carry out creative deviance. Drawing upon role theory, this study explores the impact mechanism of perceived overqualification on employee creative deviance, with leadership emergence as the mediating variable, and further examines the moderating role of job autonomy. Adopting a two-stage design, 362 valid data samples were collected from various companies, and analysis was conducted using partial least squares structural equation modeling. The results indicate a positive correlation between perceived overqualification and creative deviance. Perceived overqualification not only positively influences leadership emergence but it also indirectly affects creative deviance through leadership emergence. Furthermore, when individuals with perceived overqualification and possess a greater level of job autonomy, they are more likely to engage in creative deviant behavior. The findings contribute to understanding the mediating mechanisms and boundary conditions of employees' perceived overqualification influencing creative deviance from a positive perspective, offering valuable managerial insights for organizations.

Recognizing that enteric tuft cells can signal the presence of nematode parasites, we investigated whether tuft cells are required for the expulsion of the cestode, Hymenolepis diminuta, from the non-permissive mouse host, and in concomitant anti-helminthic responses. BALB/c and C57BL/6 mice infected with H. diminuta expelled the worms by 11 days post-infection (dpi) and displayed DCLK1+ (doublecortin-like kinase 1) tuft cell hyperplasia in the small intestine (not the colon) at 11 dpi. This tuft cell hyperplasia was dependent on IL-4Rα signalling and adaptive immunity, but not the microbiota. Expulsion of H. diminuta was slowed until at least 14 dpi, but not negated, in tuft cell-deficient Pou2f3-/- mice and was accompanied by delayed goblet cell hyperplasia and slowed small bowel transit. Worm antigen and mitogen evoked production of IL-4 and IL-10 by splenocytes from wild-type and Pou2f3-/- mice was not appreciably different, suggesting similar systemic immune reactivity to infection with H. diminuta. Wild-type and Pou2f3-/- mice infected with H. diminuta displayed partial protection against subsequent infection with the nematode Heligmosomoides bakeri. We speculate that, with respect to H. diminuta, enteric tuft cells are important for local immune events driving the rapidity of H. diminuta expulsion but are not critical in initiating or sustaining systemic Th2 responses that provide concomitant immunity against secondary infection with H. bakeri.

Gaining insights into overarching trends in chemical reaction systems is crucial for refining reaction conditions and developing novel reactions. These knowledgements include preferences for certain reagents, solvents, and functional group tolerance rules. Traditionally, synthetic chemists have relied on extensive literature searching to acquire the knowledge, a process that is both time-consuming and laborious. To streamline this process, we construct a standardized dataset and knowledge graph on an emerging domain, transition-metal-free transformations with organoborons. The dataset, compiled from organic reaction literature, includes comprehensive details of reaction scopes and conditions. The subsequent construction of a knowledge graph offers a visual representation of the reactions and their interrelationships. Through knowledge graph-based hierarchical analysis and density functional theory (DFT) calculations, we revealed the currently most frequently used reactants, synthetic conditions, and functional group rules in this field. We anticipate this knowledge graph-based approach will accelerate the acquisition and transfer of chemical reaction knowledge, catalyzing the discovery of new reactions. This work provides an automatic and adaptive framework for extracting key insights from reaction datasets to inform the design of novel reactions.

Summary: Chemical warfare agents (CWAs), epitomized by the notoriously used mustard gas (HD), represent a class of exceptionally toxic chemicals whose airborne removal is paramount for battlefield safety. This study integrates high-throughput computational screening (HTCS) with advanced machine learning (ML) techniques to investigate the efficacy of metal-organic frameworks (MOFs) in adsorbing and capturing trace amounts of HD present in the air. Our approach commenced with a comprehensive univariate analysis, scrutinizing the impact of six distinct descriptors on the adsorption efficiency of MOFs. This analysis elucidated a pronounced correlation between MOF density and the Henry coefficient in the effective capture of HD. Then, four ML algorithms were employed to train and predict the performance of MOFs. The Random Forest (RF) algorithm demonstrates strong model learning and good generalization, achieving the best prediction result of 98.3%. In a novel exploratory stride, we incorporated a 166-bit MACCS molecular fingerprinting (MF) to identify critical functional groups within adsorbents. From the top 100 MOFs analyzed, 22 optimal functional groups were identified. Leveraging these insights, we designed three innovative substructures, grounded in these key functional groups, to enhance HD adsorption efficiency. In this work, the combination of MF and ML could provide a new direction for efficient screening of MOFs for the capture of HD in the air. The outcomes of this study offer substantial potential to revolutionize the domain of CWA capture. This represents a significant stride toward developing practical solutions that enhance both environmental protection and battlefield security.

Abstract Objective Our study aimed to investigate the glucose levels in PD and controls. We also examine whether glucose control is associated with PD severity regardless of diabetic status, and test whether the correlation is mediated by cerebral small vessel disease (CSVD) burden. Methods A total of 100 patients with idiopathic PD and 100 age‐ and sex‐matched controls who underwent brain magnetic resonance imaging (MRI) were enrolled in this study. We collected the clinical data and blood parameters, including fasting blood glucose (FBG), glycated hemoglobin A1c (HbA1c), and blood lipid. Patients with PD were divided into early (n = 61) and advanced (n = 39) subgroups, based on Hoehn and Yahr (H&Y) stages. Differences between the PD and controls, PD with and without diabetes, and between two PD subgroups were compared. CSVD markers were assessed, including lacunes, white matter hyperintensities, enlarged perivascular spaces, and cerebral microbleeds. Multivariable logistic regressions were used to test the association between HbA1c and H&Y stages. Interaction between HbA1c and CSVD burden in relation to H&Y stages was also analyzed. Results PD group exhibited higher HbA1c (p

To study the alkaloids in the rhizomes of Stephania macrantha. The total alkaloids of S. macrantha were extracted by acid extraction and alkali precipitation method. Eleven alkaloids have been isolated and purified by silica gel column chromatography and preparative high performance liquid chromatography (HPLC). The structures of compounds were identified by spectroscopic methods (NMR and MS). The results were as follows: (1) Eleven compounds were designated as sinomenine (1), sinoactine (2), stepharine (3), reticuline (4), isocorydine (5), corydalmine (6), asimilobine (7), sukhodianine (8), dicentrine (9), 7-oxocrebanine (10) and palmatine (11). (2) The total alkaloids of S. macrantha and sinomenine had inhibitory activities on human lung cancer cells (A549), with IC50 values of 7.5×10-4 g·mL-1 and 6.59×10-9 g·mL-1, respectively. Compounds 2, 3, 4, 7, 8, 9 and 10 were isolated for the first time from S. macrantha. The chemical constituents from S. macrantha belong to five types of alkaloids such as morphanes, proaporphines, aporphines, benzyltetrahydroi soquinolines and protoberberines.

To decrease the consumption of energy and material resources caused by the traditional ''two-step'' process for separating propylene from the C3 crude components, including propane, propylene, methylacetylene and propadiene, this work utilizes the metal-organic frameworks (MOFs) involved ''one-step'' process to purify propylene. First, the relationship between the geometric/energy descriptors of MOFs and their performance metrics was established through univariate analysis, and results show that the top-performance MOFs can be screened by the differences of LCD, ρ, VSA and ϕ. Then, different combinations of descriptors and algorithms were used for machine learning. The combination (RF algorithm, 7 basic descriptors + PSD + MorganFPs + nodes + topologies) with the best prediction accuracy (R=0.87) for predicting the performance of MOFs was found. Finally, 4 optimal pore structures for the design of high propylene adsorption performance materials were summarized, which mainly contain cylindrical channels and spherical cavities similar in size to the target gas. The microscopic control of pore structures obtained from our bottom-up approach is useful for the development of MOFs and other nanoporous materials which can be used for ''one-step'' separation of propylene from C3 mixtures in various industrial situations.

Objectives. The aim of this study was to compare the Sniffin’ Sticks 12-identification test (SIT-12), China-modified version of the SIT-12 test (Ch-SIT-12) and brief smell identification test for Chinese (B-SITC) in Chinese population of Parkinson’s disease (PD) and multiple system atrophy (MSA). Methods. 36 patients with PD and 7 patients with MSA were enrolled in this study. Three olfactory testing methods (SIT-12, Ch-SIT-12, and B-SITC) were used to test the olfactory function in all participants. Furthermore, demographic and clinical data were collected. Results. There was no significant difference between three olfactory tests in patients with PD (B-SITC vs. SIT-12: P=0.508; Ch-SIT-12 vs. B-SITC: P=0.146; and SIT-12 vs. Ch-SIT-12: P=0.375). Tremor-dominant (TD) subtypes have better olfactory function than akinetic-rigid dominant (ARD) subtypes when using Ch-SIT-12 (77.8% vs. 29.6%, P=0.019) or B-SITC (55.6% vs. 14.8%, P=0.026). There was a statistical difference between the PD and MSA using Ch-SIT-12 to test the olfactory function (P=0.046). Conclusions. Our results indicated that SIT-12, Ch-SIT-12 and B-SITC can be used for the detection of olfactory dysfunction in Chinese population of PD. TD subtypes may have better olfactory function than ARD subtypes. In addition, Ch-SIT-12 may be used to differentiate PD from MSA, but that should be confirmed in a larger population.

Biodiversity is the essential foundation of ecosystem stability and significantly influences human health. However, the specific impacts of broadly varied biodiversity levels across diverse greenspaces on mental well-being remain unclear. In this randomized controlled trial, immersive virtual reality (VR) auditory-visual simulations, emulating real biodiversity scenarios, were employed to investigate the effect of diverse biodiversity levels on stress and affect. After an induced stress phase, participants (N = 90) were randomly assigned to a ten-minute immersion in one of three settings: urban park, peri-urban park, or nature conservation area. Physiological responses were measured via skin conductance level (SCL) and significant skin conductance responses (nSCR), while psychological responses were evaluated using Positive Affect and Negative Affect Scale (PANAS). Additionally, the Perceived Restorativeness Scale (PRS) was employed to evaluate restoration potential. Repeated measures analysis of variance revealed that immersion in the peri-urban park and nature conservation area was associated with a significantly faster and more substantial decrease in SCL compared to the urban park. nSCR in the nature conservation area remained significantly lower than in the urban park. While immersion in all three natural environments significantly diminished negative affect, the nature conservation scenario was associated with a substantial decline in positive affect and received the lowest rating on the subjective restorativeness. A psychological benefit threshold related to biodiversity was observed, in contrast to the absence of a corresponding physiological threshold. This disparity suggests that an innate genetic affinity for high biodiversity may persists, unaffected by acquired experiences. Our study underscores the stress recovery benefits of high-value ecological environments, thereby fostering an avenue for further investigations into human-ecological health interconnections.

Climate change and the rapid loss of biodiversity pose threats to human survival and development. However, there remains a limited understanding of the relationship between biodiversity and human health, especially in the context of developing countries. This study pursues two objectives: (1) to explore the relationship between biodiversity and human health; and (2) to investigate how this relationship varies across different economic regions. Using a cross-sectional design, we analyzed data from 31 provinces, autonomous regions and municipalities across China. The dataset encompassed information on biodiversity (animals, plants, and fungi), subjective health, and mental health. We employed a two-stage least squares analysis, designating the proportion of part-time rangers and the completion of investments in wild fauna and flora per unit area as instrumental variables. Subsequently, we examined the moderating effect of the average Per Capita Disposable Income on the relationship between biodiversity and mental health. Additionally, we conducted grouped regression analyses for three regions with varying levels of economic development. The regression model incorporated macroecological, macroeconomic, and sociodemographic data as control variables. The results indicated a correlation between bird, plant species richness, biological richness (the total number of plants, animals, and fungi), and mental health. However, these biodiversity measures were significantly associated with poor subjective health. Additionally, the contribution of biological richness to mental health declines as the average Per Capita Disposable Income rises. The relationship between biodiversity and mental health was significantly negative in regions with low economic development, significantly positive in medium economic development regions, and not significant in high economic development regions. The analysis indicates that as the economy grows, there may exist a lower and upper threshold at which biodiversity exerts a positive impact on mental health. These thresholds merit further investigation. This observed gap might be attributed to the diminishing natural experiences in regions undergoing rapid economic development. The findings of this study offer insights that could guide policy decisions in developing countries, balancing biodiversity preservation, economic growth, and public health.

Global warming and the urban heat island effect has aroused the attention of research on the outdoor thermal environment. As outdoor spaces often used by citizens, streets play an important role in improving the thermal environment. In this study, six factors relating to street geometries and tree configurations in Busan are measured and quantified to form 32 typical scenarios. The degree of importance of these six factors is evaluated based on ENVI-met simulation results, and GeoDetector is introduced to evaluate the interactions between the factors and their impacts on the outdoor thermal environment. This study confirms the significantly higher impact of street geometry factors on the air temperature and physiological equivalent temperature compared to tree configuration factors. Particularly, Hb/Ws shows the most significant impact during the research period. The impact of interactions between any two factors of street geometry is much higher than that of interactions between the geometry and tree configuration factors and that of interactions between the tree configuration factors. We recommend dynamically adjusting the relationship between street geometry and tree configurations in different situations to improve the outdoor thermal environment, especially at noon and in the afternoon.

Introduction: Alexithymia and perceived stress have been recognized as risk factors for suicide in patients with major depressive disorder (MDD). However, few studies have been conducted to examine the relationship between these factors. Methods: A cross-sectional study was conducted on 105 MDD patients. Alexithymia was assessed by the 20-Item Toronto Alexithymia Scale (TAS), perceived stress was assessed by the Perceived Stress Scale (PSS), severity of depression was assessed by the 17-item Hamilton Depression Rating Scale (HAMD), and suicidal ideation was assessed by the self-report Beck Scale for Suicide Ideation (SSI). A sequential mediation model was established to test the mediating effects of perceived stress and severity of depression on the association between alexithymia and suicidal ideation. Results: 81 of the 105 participants (77.14 %) had suicidal ideation. Patients with suicidal ideation had greater difficulty in identifying feelings (DIF) (p = 0.046), higher severity of depression (p = 0.005) and perceived stress (p = 0.003). DIF subscale score of TAS was associated with perceived stress (r = 0.292, p = 0.003), severity of depression (r = 0.349, p

IntroductionReversible cerebral vasoconstriction syndrome (RCVS) is a potentially life-threatening neurological disorder, rarely linked to intracranial hypotension. The presentation showed a patient with intracranial hypotension after peridural anesthesia who experienced RCVS during the early postpartum period, suggesting a potential involvement of intracranial hypotension in RCVS occurrence.Case reportA young female of 29 years of age initially developed an orthostatic headache after undergoing a painless delivery with lumbar epidural anesthesia. Intracranial hypotension was considered the underlying cause. Her headache was partially resolved after intravenous fluid therapy and strict bed rest. After 2 days, the patient had a new onset thunderclap headache with generalized seizures, cortical blindness, and elevated blood pressure. An MRI scan revealed high signal intensity within the temporal, parietal, and occipital lobes, left caudate nucleus, and right cerebellum on T2-FLAIR imaging with vasogenic edema. MR angiography indicated multifocal, segmental, diffuse narrowing affecting the cerebral arteries that are large and medium. An RCVS2 score was six, and the patient was diagnosed with RCVS. She was managed conservatively, quickly improving her symptoms. After 10 days, a follow-up MRI indicated a significant reduction in the abnormal signal, and a substantial resolution of the constriction of the cerebral artery constriction was confirmed by MR angiography.ConclusionIntracranial hypotension could potentially lead to RCVS in postpartum patients, and it may be triggered by cerebral vasospasm secondary to intracranial hypotension.

Sila-substituted compounds have potential application in medicinal chemistry, but their preparation from the corresponding carbon analogues remains challenging. Here, the authors report the synthesis of sila-benzoazoles via hydrosilylation and rearrangement of benzoazoles; the reaction is enabled by a Lewis acid.

Background Short tandem repeats (STR) are highly polymorphic DNA markers utilised in forensic personal identification and human population genetic research. Guizhou Tujia is one of the ancient minority groups in southwest China, however, the population has not been studied using the highly discriminating 23 STR Huaxia Platinum Kit. Aim To obtain genetic data from 23 autosomal STRs in Guizhou Tujia and examine the population’s relationship with others. Subjects and methods A total of 480 individuals from the Guizhou Tujia population were analysed using 23 STR loci of Huaxia Platinum Kit. Allele frequencies and forensic parameters were estimated. Population genetic relationships were calculated by Nei’s genetic distances and visualised using a variety of biostatistical methods. Results A total of 264 alleles were found, with allelic frequencies ranging from 0.0010 to 0.5104. The combined discrimination power (CDP) and the combined probability of paternity (CPE) of 23 STR loci were 0.9999999999999999999999999996 and 0.999999999710422, respectively. Guizhou Tujia showed closer genetic relationships with Hubei Tujia, Guizhou Gelao, and Guizhou Miao than with other populations. Conclusion We first obtained the population genetic data of Guizhou Tujia using the 23 STR system and demonstrated its value in forensic applications. Comprehensive population comparisons showed an evident genetic affinity pattern between populations that are geographically, ethnically and linguistically related.

The shape and topology of pores have significant impacts on the gas storage properties of nanoporous materials. Metal–organic frameworks (MOFs) are ideal materials with which to tailor to the needs of specific applications, due to properties such as their tunable structure and high specific surface area. It is, therefore, particularly important to develop descriptors that accurately identify the topological features of MOF pores. In this work, a topological data analysis method was used to develop a topological descriptor, based on the pore topology, which was combined with the Extreme Gradient Boosting (XGBoost) algorithm to predict the adsorption performance of MOFs for methane/ethane/propane. The final results show that this descriptor can accurately predict the performance of MOFs, and the introduction of the topological descriptor also significantly improves the accuracy of the model, resulting in an increase of up to 17.55% in the R2 value of the model and a decrease of up to 46.1% in the RMSE, compared to commonly used models that are based on the structural descriptor. The results of this study contribute to a deeper understanding of the relationship between the performance and structure of MOFs and provide useful guidelines and strategies for the design of high-performance separation materials.

Street trees are essential to urban ecological benefits and human well-being. The canopy morphology relates to the green view index (GVI), which needs to be calculated based on specific tree species. This study conducts a field study on 760 street trees of 3 species from the pedestrian perspective, and explores the differences in canopy GVI and its factors of different specifications of street trees using DBH grading. The results indicate that (1) street trees can provide 20% of the GVI in unilateral streets, with 13% of the GVI in a single canopy. (2) A flat oval crown with a wider canopy width is more effective in providing GVI than a long oval crown, and a CW with a higher canopy GVI highlights this advantage. (3) DBHs of 30 and 40 can be used as grading indicators for Cinnamomum camphora, and the specification requirements can be reduced for Southern magnolia and Chinese privet. (4) The concept of DE is introduced, and new parameters related to the central crown have significant impacts on GVI. The conclusions can improve the GVI application in urban greenery planning as well as have certain implications for the cost management of future seedling cultivation.

Influenza virus, with a global distribution, diverse animal host range and multiple virus subtypes, has caused several pandemics. To better prepare for the emergence of new subtypes and the possible threat of the next pandemic, the global status of animal influenza must be defined and documented. We created a global database of animal influenza events by searching scientific databases and the primary literature on animal influenza-related events up to and including 2016. The temporal, spatial and host distribution of animal influenza and the diversity of influenza subtypes in different regions were analyzed. A total of 70,472 records and 4712 events of animal influenza throughout the world were identified. Events involving subtypes H5N2, H7N7 and H7N9 were relatively constant, with a slow upward trend during the past decade. Asia was the region with the most clusters of events. Poultry was the main host reported in Asia and Africa, and wild birds in Europe and North America. We found that wild birds carried a very rich array of virus subtypes, a warning for the possible generation of reassortment viruses with pandemic potential. Influenza virus subtype diversity - a risk for virus reassortment - was greatest in Asia, North America and Europe. Our database provides a comprehensive overview of the historical and current status of animal influenza events throughout the world. Influenza surveillance needs to be strengthened in some countries and regions to prevent the emergence of new subtypes. Importantly, improvement of the global influenza surveillance system and structures to enable sharing of surveillance data is very much needed to prepare for the next pandemic.

Endoscopic dilation (ED) is the mainstream treatment for esophageal stricture after endoscopic submucosal dissection (ESD). However, some complex esophageal strictures do not respond well to dilation. Endoscopic radial incision (ERI) has proved to be effective in treating anastomotic strictures, but it is rarely used to treat post-ESD esophageal strictures due to technical difficulties and risks, not to mention the optimal method and timing to perform ERI. Here, we developed an integrated procedure in which ED was performed first, followed by ERI on the stiff scars that remained intact after dilation. The ED + ERI procedure resulted in complete, uniform expansion of the esophageal lumen. Between 2019 and 2022, 5 post-ESD patients who received a median number of 11 sessions of ED (range, 4–28) of ED over a period of 322 days (range, 246–584) but still had moderate to severe dysphagia were admitted. 2 or 3 sessions of ED + ERI were performed for each patient interspersed with ED. After a median number of 4 treatments (range, 2–9), all patients were symptom-free or had minimal symptoms. No serious complications occurred in any patients who underwent ED + ERI. Therefore, ED + ERI is safe, feasible, and may serve as a useful therapeutic method for refractory esophageal stricture after ESD.

Background. Ventilator-associated pneumonia (VAP) is among the most important hospital-acquired infections in an intensive-care unit setting. However, clinical practice lacks effective theoretical tools for preventing VAP in the elderly. Aim. To describe the independent factors associated with VAP in elderly intensive-care unit (ICU) patients on mechanical ventilation (MV) and to construct a risk prediction model. Methods. A total of 1851 elderly patients with MV in ICUs from January 2015 to September 2019 were selected from 12 tertiary hospitals. Study subjects were divided into a model group (n = 1219) and a validation group (n = 632). Two groups of patients were divided into a VAP group and a non-VAP group and compared. Univariate and logistic regression analyses were used to explore influencing factors for VAP in elderly ICU patients with MV, establish a risk prediction model, and draw a nomogram. We used the area under the receiver operating characteristic curve (AUROC) and the Hosmer–Lemeshow goodness-of-fit test to evaluate the predictive effect of the model. Findings regarding the length of ICU stay, surgery, C-reactive protein (CRP), and the number of reintubations were independent risk factors for VAP in elderly ICU patients with MV. Predictive-model verification results showed that the area under the curve (AUC) of VAP risk after MV in the modeling and verification groups was 0.859 and 0.813 (P

Wheat is one of the most important food crops in the world and drought can severely impact on wheat productivity. The identification and deployment of genes for improved water use efficiency (WUE) can help alleviate yield loss under water limitation. In this study, a high-density genetic linkage map of wheat recombinant inbred lines (Ningchun 4 x Ningchun 27) containing 8751 specific locus amplified fragment (SLAF) tags (including 14757 SNPs), with a total map distance of 1685 cM and an average inter-marker map distance of 0.19 cM was constructed by SLAF-seq technology. The economic yield WUE and nine related traits under three water treatments was monitored over four years. The results showed that loci conditioning WUE were also associated with grain carbon isotope discrimination (CID), flag leaf chlorophyll content, plant height, 1000-grain weight, grain weight per spike and grain number per spike. One locus on chromosome 2B explained 26.3% WUE variation in multiple environments. Under good soil moisture conditions before flowering, the high CID genotype QWue.acn-2BNingchun 27, was associated with WUE, high grain weight per spike, and kilo-grain weight. Under rain-fed conditions, the low CID genotype QWue.acn-2BNingchun 4 tended to maintain more spike number and was associated with improved WUE and yield. The introduction of good chromosome fragments of QWue.acn-2B into elite lines by molecular marker assisted selection will boost up the cultivation of high-yield and water-saving wheat varieties.

Abstract Objective Medical disorders in patients with bipolar disorder (BD) have attracted more and more attention. So far, there is still a lack of studies on this issue utilizing large sample sizes in the Chinese sample. Therefore, we conducted this study to explore the clinical characteristics of BD patients comorbid medical disorders in a relatively large Chinese sample. Methods This was a cross-sectional study including 1,393 BD patients (882 patients with medical disorders and 511 patients without medical disorders). Their demographic and clinical characteristics were obtained by the Hospital Information System and self-designed questionnaires. Results The comorbidity rate of medical disorders in BD was 63.32%. The average number of medical disorders for a BD patient was 2.69. The top five comorbid medical disorders in BD patients were circulatory system diseases (19%), nervous system diseases (18%), endocrine and metabolic diseases (17%), digestive system diseases (16%), and respiratory system diseases (8%). BD patients with comorbid medical disorders had an older average age, lower education level, longer illness course, later onset age, lower ratio of psychotic features, more admission numbers, higher ratio of smoking and drinking alcohol, more number of manic episodes (All P

ACCESS-S2 is a major upgrade to the Australian Bureau of Meteorology’s multi-week to seasonal prediction system. It was made operational in October 2021, replacing ACCESS-S1. The focus of the upgrade is the addition of a new weakly coupled data assimilation system to provide initial conditions for atmosphere, ocean, land and ice fields. The model is based on the UK Met Office GloSea5-GC2 seasonal prediction system and is unchanged from ACCESS-S1, aside from minor corrections and enhancements. The performance of the assimilation system and the skill of the seasonal and multi-week forecasts have been assessed and compared to ACCESS-S1. There are improvements in the ACCESS-S2 initial conditions compared to ACCESS-S1, particularly for soil moisture and aspects of the ocean, notably the ocean currents. More realistic soil moisture initialisation has led to increased skill for forecasts over Australia, especially those of maximum temperature. The ACCESS-S2 system is shown to have increased skill of El Nino–Southern Oscillation forecasts over ACCESS-S1 during the challenging autumn forecast period. Analysis suggests that ACCESS-S2 will deliver improved operational forecast accuracy in comparison to ACCESS-S1. Assessments of the operational forecasts are underway. ACCESS-S2 represents another step forward in the development of seasonal forecast systems at the Bureau of Meteorology. However, key rainfall and sea surface temperature biases in ACCESS-S1 remain in ACCESS-S2, indicating where future efforts should be focused.

Aiming to efficiently capture the formaldehyde (HCHO) with low content in the air exceeding the standard, 31,399 hydrophobic metal–organic frameworks (MOFs) were first selected from 137,953 hypothetical MOFs to calculate their formaldehyde adsorption performance, namely, adsorption capacity (NHCHO) and selectivity (SHCHO/N2+O2) by molecular simulation and machine learning (ML). To combine the SHCHO/N2+O2 and NHCHO, a new performance metric, the tradeoff between selectivity and capacity (TSC) was proposed to identify more reasonably the top-performing MOFs. The MOFs were divided into three datasets (i.e., all of the MOFs (AM), MOFs with top 5% of SHCHO/N2+O2 (PS) and MOFs with top 5% of NHCHO (PN)) to scrutinize and explore the characteristics of different materials capturing formaldehyde from the air (N2 and O2). Furthermore, after four ML algorithms (the back propagation neural network (BPNN), support vector machine (SVM), extreme learning machine (ELM), and random forest (RF)) are applied to quantitatively assess the prediction effects of performance indexes in different datasets, RF algorithm with the most accurate prediction revealed that the TSC has strong correlations with the MOF descriptors in PS dataset. In view of 14.10% of the promising MOFs occupied PN, the design paths of excellent adsorbents for six MOF descriptors were quantitatively determined, especially for the Henry's coefficient (KHCHO) and heat of adsorption of formaldehyde (Q0st). Their probabilities of obtaining excellent MOFs could reach 100% and 77.42%, respectively, and both the relative importance and the trends of univariate analysis coherently confirm the important positions of KHCHO and Q0st. Finally, 20 best MOFs were identified for the single-step separation of formaldehyde with low concentration. The microscopic insights and structure-performance relationship predictions from this computational and ML study are useful toward the development of new MOFs for the capture of formaldehyde from air.

Abstract Background Studies on the inhibition of inflammation by infection with helminth parasites have, until recently, overlooked a key determinant of health: the gut microbiota. Infection with helminths evokes changes in the composition of their host’s microbiota: one outcome of which is an altered metabolome (e.g., levels of short-chain fatty acids (SCFAs)) in the gut lumen. The functional implications of helminth-evoked changes in the enteric microbiome (composition and metabolites) are poorly understood and are explored with respect to controlling enteric inflammation. Methods Antibiotic-treated wild-type, germ-free (GF) and free fatty-acid receptor-2 (ffar2) deficient mice were infected with the tapeworm Hymenolepis diminuta, then challenged with DNBS-colitis and disease severity and gut expression of the il-10 receptor-α and SCFA receptors/transporters assessed 3 days later. Gut bacteria composition was assessed by 16 s rRNA sequencing and SCFAs were measured. Other studies assessed the ability of feces or a bacteria-free fecal filtrate from H. diminuta-infected mice to inhibit colitis. Results Protection against disease by infection with H. diminuta was abrogated by antibiotic treatment and was not observed in GF-mice. Bacterial community profiling revealed an increase in variants belonging to the families Lachnospiraceae and Clostridium cluster XIVa in mice 8 days post-infection with H. diminuta, and the transfer of feces from these mice suppressed DNBS-colitis in GF-mice. Mice treated with a bacteria-free filtrate of feces from H. diminuta-infected mice were protected from DNBS-colitis. Metabolomic analysis revealed increased acetate and butyrate (both or which can reduce colitis) in feces from H. diminuta-infected mice, but not from antibiotic-treated H. diminuta-infected mice. H. diminuta-induced protection against DNBS-colitis was not observed in ffar2 −/− mice. Immunologically, anti-il-10 antibodies inhibited the anti-colitic effect of H. diminuta-infection. Analyses of epithelial cell lines, colonoids, and colon segments uncovered reciprocity between butyrate and il-10 in the induction of the il-10-receptor and butyrate transporters. Conclusion Having defined a feed-forward signaling loop between il-10 and butyrate following infection with H. diminuta, this study identifies the gut microbiome as a critical component of the anti-colitic effect of this helminth therapy. We suggest that any intention-to-treat with helminth therapy should be based on the characterization of the patient’s immunological and microbiological response to the helminth.

Natural enzymes possess remarkable catalytic activity and high substrate specificity. Many efforts have been dedicated to construct artificial enzymes with high catalytic activity. However, how to mimic the exquisite substrate specificity of a natural enzyme remains challenging because of the complexity of the enzyme structure. Here, we report artificial carboxylesterases that are specific for short chain fatty acids and were constructed via peptide self-assembly. These artificial systems have esterase-like activity rather than lipase-like activity towards p-nitrophenyl esters. The designer peptides self-assembled into nanofibers with strong β-sheet character. The extending histidine units and the hydrophobic edge of the fibrillar structure collectively form the active center of the artificial esterase. These artificial esterases show substrate specificity for short-chain acids esters. Moreover, 1-isopropoxy-4-nitrobenzene could function as a competitive inhibitor of hydrolysis of p-nitrophenyl acetate for an artificial esterase.

The capture of trace amounts of non-methane hydrocarbons (NMHCs) from air due to the toxicity of volatile organic compounds is a significant challenge. A total of 31399 hydrophobic metal–organic frameworks (MOFs) were first screened from 137953 hypothetical MOFs using high-throughput computational screening (HTCS), and their performance indices (adsorption capacity and selectivity) for the adsorption of NMHCs (C3–C6) were obtained by molecular simulations. The discovery of a “second peak” near twice the kinetic diameter of the corresponding NMHC provided more choices for excellent MOFs that adsorb NMHCs. Four machine learning (ML) classification and regression algorithms predicted the performance of MOFs, and the relative importance values of the six descriptors were determined. The combination of the Random Forests algorithm and Molecular ACCess Systems molecular fingerprint (MF) had an excellent predictive ability for MOFs. According to the performance, the fingerprint commonalities of the 100 top-performing MOFs were counted, and the excellent bits (EBs) that could promote the performance were defined. Finally, new substructures containing all of the EBs were designed for each NMHC to build a new MOF database. This work combined the HTCS, ML, and MF to provide a detailed insight into the design of efficient MOFs for adsorbing NMHCs.

Brain activity is time varying and dynamic, even in the resting state. However, little attention has been paid to the dynamic alterations in regional brain activity in Parkinson’s disease (PD). We aimed to test for differences in dynamic regional homogeneity (dReHo) between PD patients and healthy controls (HCs) and to further investigate the pathophysiological meaning of this altered dReHo in PD. We included 57 PD patients and 31 HCs with rs-fMRI scans and neuropsychological examinations. Then, ReHo and dReHo were calculated for all subjects. We compared ReHo and dReHo between PD patients and HCs and then analyzed the associations between altered dReHo variability and clinical/neuropsychological measurements. Support vector machines (SVMs) were also used to assist in differentiating PD patients from HCs using the classification values of dReHo. The results showed that PD patients had increased ReHo in the bilateral medial temporal lobe and decreased ReHo in the right posterior cerebellar lobe, right precentral gyrus, and supplementary motor area, compared with controls. The coefficient of variation (CV) of dReHo was considerably higher in the precuneus in PD patients compared with HCs, and the CV of dReHo in the precuneus was found to be highly associated with HAMD, HAMA, and NMSQ scores. Multiple linear regression analysis controlling for demographic, clinical, and neuropsychiatric variables confirmed the association between altered dReHo and HAMD. Using the leave-one-out cross validation procedure, 98% (p < 0.001) of individuals were properly identified using the SVM classifier. These results provide new evidence for the aberrant resting-state brain activity in the precuneus of PD patients and its role in neuropsychiatric symptoms in PD.

Abstract Background Convenient and precise assessment of the severity in coronavirus disease 2019 (COVID-19) contributes to the timely patient treatment and prognosis improvement. We aimed to evaluate the ability of CT-based radiomics nomogram in discriminating the severity of patients with COVID-19 Pneumonia. Methods A total of 150 patients (training cohort n = 105; test cohort n = 45) with COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR) test were enrolled. Two feature selection methods, Max-Relevance and Min-Redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO), were used to extract features from CT images and construct model. A total of 30 radiomic features were finally retained. Rad-score was calculated by summing the selected features weighted by their coefficients. The radiomics nomogram incorporating clinical-radiological features was eventually constructed by multivariate regression analysis. Nomogram, calibration, and decision-curve analysis were all assessed. Results In both cohorts, 40 patients with COVID-19 pneumonia were severe and 110 patients were non-severe. By combining the 30 radiomic features extracted from CT images, the radiomics signature showed high discrimination between severe and non-severe patients in the training set [Area Under the Curve (AUC), 0.857; 95% confidence interval (CI), 0.775–0.918] and the test set (AUC, 0.867; 95% CI, 0.732–949). The final combined model that integrated age, comorbidity, CT scores, number of lesions, ground glass opacity (GGO) with consolidation, and radiomics signature, improved the AUC to 0.952 in the training cohort and 0.98 in the test cohort. The nomogram based on the combined model similarly exhibited excellent discrimination performance in both training and test cohorts. Conclusions The developed model based on a radiomics signature derived from CT images can be a reliable marker for discriminating the severity of COVID-19 pneumonia.

ABSTRACT Communication between plants and microorganisms is vital because it influences their growth, development, defense, propagation, and metabolism in achieving maximal fitness. N-acetylglucosamine (N-GlcNAc), the building block of bacterial and fungal cell walls, was first reported to promote tomato plant growth via stimulation of microorganisms typically known to dominate the tomato root rhizosphere, such as members of Proteobacteria and Actinobacteria. Using KEGG pathway analysis of the rhizosphere microbial operational taxonomic units, the streptomycin biosynthesis pathway was enriched in the presence of N-GlcNAc. The biosynthesis of 3-hydroxy-2-butanone (acetoin) and 2,3-butanediol, two foremost types of plant growth promotion-related volatile organic compounds, were activated in both Bacillus subtilis and Streptomyces thermocarboxydus strains when they were cocultured with N-GlcNAc. In addition, the application of N-GlcNAc increased indole-3-acetic acid production in a dose-dependent manner in strains of Bacillus cereus, Proteus mirabilis, Pseudomonas putida, and S. thermocarboxydus that were isolated from an N-GlcNAc-treated tomato rhizosphere. Overall, this study found that N-GlcNAc could function as microbial signaling molecules to shape the community structure and metabolism of the rhizosphere microbiome, thereby regulating plant growth and development and preventing plant disease through complementary plant–microbe interactions. IMPORTANCE While the benefits of using plant growth-promoting rhizobacteria (PGPRs) to enhance crop production have been recognized and studied extensively under laboratory conditions, the success of their application in the field varies immensely. More fundamentally explicit processes of positive, plant–PGPRs interactions are needed. The utilization of organic amendments, such as chitin and its derivatives, is one of the most economical and practical options for improving soil and substrate quality as well as plant growth and resilience. In this study, we observed that the chitin monomer N-GlcNAc, a key microbial signaling molecule produced through interactions between chitin, soil microbes, and the plants, positively shaped the community structure and metabolism of the rhizosphere microbiome of tomatoes. Our findings also provide a new direction for enhancing the benefits and stability of PGPRs in the field.

Abstract Background New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was − 2.15 points (95% confidence interval, − 3.07 to − 1.23; p

With the global epidemic of SARS-CoV-2, it is important to effectively monitor the variation, haplotype subgroup epidemic trends and key mutations of SARS-CoV-2 over time. This is of great significance to the development of new vaccines, the update of therapeutic drugs, and the improvement of detection methods. The AutoVEM tool developed in the present study could complete all mutations detections, haplotypes classification, haplotype subgroup epidemic trends and candidate key mutations analysis for 131,576 SARS-CoV-2 genome sequences in 18 h on a 1 core CPU and 2 GB RAM computer. Through haplotype subgroup epidemic trends analysis of 131,576 genome sequences, the great significance of the previous 4 specific sites (C241T, C3037T, C14408T and A23403G) was further revealed, and 6 new mutation sites of highly linked (T445C, C6286T, C22227T, G25563T, C26801G and G29645T) were discovered for the first time that might be related to the infectivity, pathogenicity or host adaptability of SARS-CoV-2. In brief, we proposed an integrative method and developed an efficient automated tool to monitor haplotype subgroup epidemic trends and screen for the candidate key mutations in the evolution of SARS-CoV-2 over time for the first time, and all data could be updated quickly to track the prevalence of previous key mutations and new candidate key mutations because of high efficiency of the tool. In addition, the idea of combinatorial analysis in the present study can also provide a reference for the mutation monitoring of other viruses.

In our previous work, we developed an automated tool, AutoVEM, for real-time monitoring the candidate key mutations and epidemic trends of SARS-CoV-2. In this research, we further developed AutoVEM into AutoVEM2. AutoVEM2 is composed of three modules, including call module, analysis module, and plot module, which can be used modularly or as a whole for any virus, as long as the corresponding reference genome is provided. Therefore, it’s much more flexible than AutoVEM. Here, we analyzed three existing viruses by AutoVEM2, including SARS-CoV-2, HBV and HPV-16, to show the functions, effectiveness and flexibility of AutoVEM2. We found that the N501Y locus was almost completely linked to the other 16 loci in SARS-CoV-2 genomes from the UK and Europe. Among the 17 loci, 5 loci were on the S protein and all of the five mutations cause amino acid changes, which may influence the epidemic traits of SARS-CoV-2. And some candidate key mutations of HBV and HPV-16, including T350G of HPV-16 and C659T of HBV, were detected. In brief, we developed a flexible automated tool to analyze candidate key mutations and epidemic trends for any virus, which would become a standard process for virus analysis based on genome sequences in the future.

Wheat yield is highly correlated with plant height, heading date, spike characteristics, and kernel traits. In this study, we used the wheat55K single nucleotide polymorphism array to genotype a recombinant inbred line population of 165 lines constructed by crossing two tetraploid wheat materials, Icaro and Y4. A genetic linkage map with a total length of 6244.51 cM was constructed, covering 14 chromosomes of tetraploid wheat. QTLs for 12 important agronomic traits, including plant height (PH), heading date (HD), awn color (AC), spike-branching (SB), and related traits of spike and kernel, were mapped in multiple environments, while combined QTL-by-environment interactions and epistatic effects were analyzed for each trait. A total of 52 major or stable QTLs were identified, among which may be some novel loci controlling PH, SB, and kernel length-width ratio (LWR), etc., with LOD values ranging from 2.51 to 54.49, thereby explaining 2.40–66.27% of the phenotypic variation. Based on the ‘China Spring’ and durum wheat reference genome annotations, candidate genes were predicted for four stable QTLs, QPH.nwafu-2B.2 (165.67–166.99 cM), QAC.nwafu-3A.1 (419.89–420.52 cM), QAC.nwafu-4A.1 (424.31–447.4 cM), and QLWR.nwafu-7A.1 (166.66–175.46 cM). Thirty-one QTL clusters and 44 segregation distortion regions were also detected, and 38 and 18 major or stable QTLs were included in these clusters and segregation distortion regions, respectively. These results provide QTLs with breeding application potential in tetraploid wheat that broadens the genetic basis of important agronomic traits such as PH, HD, AC, SB, etc., and benefits wheat breeding.

We investigated retinal structure changes in patients with Parkinson’s disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and controls, and explored the value of this method in differential diagnosis. Spectral domain optical coherence tomography (SD-OCT) was used to measure peripapillary retinal nerve fiber layer (pRNFL) thickness, and macular thickness and volume. PSP patients showed higher temporal pRNFL thickness than PD and MSA patients. Peripapillary RNFL thickness could be used for discriminating PSP from MSA and PD. PD and MSA patients showed retinal thinning in the foveal center circle and nasal inner sectors compared to controls. Macular thickness and volume could be used for discriminating MSA from PD. There were negative correlations between disease duration and OCT parameters in PD, MSA, and PSP, independent of age, sex ratio, and the side of the eye. PD and atypical parkinsonism correlate with specific patterns of retina alterations. OCT could be a biomarker for differential diagnosis and progression evaluation of parkinsonian syndrome.

Gastric cancer (GC) is a very common malignancy with a poor prognosis, and its occurrence and development are closely related to epigenetic modifications. Methylation of DNA before or during gastric cancer is an interesting research topic. This article reviews the studies on DNA methylation related to the cause, diagnosis, treatment, and prognosis of gastric cancer and aims to find cancer biomarkers to solve major human health problems.

Orientational chirality was discovered and characterized by a C(sp)–C(sp3) axis-anchored chiral center and a remotely anchored blocker. X-ray structural analysis proved that orientatiomers are stabilized by through-space functional groups, making it possible for 1 R- or S-chiral center to exhibit 3 orientational isomers simply by rotating operations. A new model system was proposed, fundamentally different from the traditional Felkin–Ahn-type or Cram-type models. In these traditional models, chiral C(sp3) center and blocking C(sp2) carbons are connected adjacently, and there exist 6 energy barriers during rotating along the C(sp2)−C(sp3) axis. In comparison, the present orientational chirality model shows that a chiral C(sp)–C(sp3) carbon is remotely located from a blocking group. Thus, it is focused on the steric dialog between a chiral C(sp3) center and a remotely anchored functional group. There exist 3 energy barriers for either (R)– or (S)–C(sp)–C(sp3) stereogenicity in the new model. Chiral amide auxiliary was proven to be an excellent chiral auxiliary in controlling rotations of orientatiomers to give complete stereoselectivity. The asymmetric synthesis of individual orientatiomers was conducted via multistep synthesis by taking advantage of the Suzuki–Miyaura cross-coupling and Sonogashira coupling reactions. Density functional theory computational study presented optimized conformers and relative energies for individual orientatiomers. This discovery would be anticipated to result in a new stereochemistry topic and have a broad impact on chemical, biomedical, and material sciences in the future.

Photocatalysis is considered to be a green and promising technology for transforming organic contaminants into nontoxic products. In this work, a CuO/tourmaline composite with zero-dimensional/two-dimensional (0D/2D) CuO architecture was successfully obtained via a facile hydrothermal process, and its photocatalytic activity was evaluated by the degradation of methylene blue (MB). Surface element valence state and molecular vibration characterization revealed that CuO chemically interacted with tourmaline via Si–O–Cu bonds. The specific surface area of the CuO/tourmaline composite (23.60 m2 g−1) was larger than that of the pristine CuO sample (3.41 m2 g−1). The CuO/tourmaline composite exhibited excellent photocatalytic activity for the degradation of MB, which was ascribed to the increase in the quantity of the adsorption-photoreactive sites and the efficient utilization of the photoinduced charge carriers. This study provides a facile strategy for the construction of 0D/2D CuO structures and the design of tourmaline-based functional composite photocatalysts for the treatment of organic contaminants in water.

Background: The aim of this study was to evaluate the glymphatic system activity in patients with Parkinson’s disease (PD) using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) methods.Methods: In total, 71 patients with idiopathic PD and 36 age- and sex-matched normal controls (NCs) were involved. Patients with PD were divided into early (n = 35) and late (n = 36) subgroups, based on Hoehn and Yahr (HY) stages. We calculated the diffusivity along the perivascular spaces (ALPS), as well as projection fibers and association fibers separately, to acquire the ALPS index. Enlarged perivascular spaces (EPVS) and periventricular white matter hyperintensities were also rated. Differences in ALPS index between the PD group and NCs and between two PD subgroups and NCs were compared. In addition, a multivariate logistic regression analysis was conducted to investigate the association between ALPS index and clinical variables.Results: Patients with PD revealed lower ALPS index than NCs (p = 0.010). The late PD group exhibited significantly lower ALPS index than NCs (p = 0.006). However, there were no marked differences noticed in ALPS index between NCs and early PD group and between the two PD subgroups. In the early PD group, there was a significantly positive correlation between ALPS index and Mini-Mental State Examination (MMSE) score (β = 0.021, p = 0.029) and a negative correlation between ALPS index and EPVS score (β = −0.050, p = 0.034), after controlling for multiple variables. In the late PD group, ALPS index was inversely associated with age (β = −0.012, p = 0.004).Conclusion: Impairment of the glymphatic system is involved in PD. DTI-ALPS index could be a promising biomarker of glymphatic system in PD.

Circular RNA RNF13 (circ-RNF13; ID: hsa_circ_0067717) is newly identified to be abnormally upregulated in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) patients. However, its role and mechanism remain to be further annotated. First of all, real-time quantitative PCR (RT-qPCR) was utilized to examine RNA expression, and circ-RNF13 was upregulated in HBV-infected human HCC tissues and HBV-expressing cells (Huh7-HBV and Hep3B-HBV), accompanied with TGFβ-induced factor homeobox 2 (TGIF2) upregulation and microRNA (miR)-424-5p downregulation. Loss-of-functional experiments were performed using MTS assay, colony formation assay, flow cytometry, enzyme-linked immunosorbent assay, transwell assay, and xenograft tumor model. As a result, blocking circ-RNF13 enhanced the apoptosis rate of Huh7-HBV and Hep3B-HBV cells, but inhibited cell proliferation, colony formation, migration, and invasion in vitro, along with suppressed tumor growth in vivo. Besides, RT-qPCR data showed that HBV DNA copies and levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were diminished by circ-RNF13 knockdown in Huh7-HBV and Hep3B-HBV cells. Mechanistically, circ-RNF13 and TGIF2 could directly interacting with miR-424-5p according to dual-luciferase reporter assay, suggesting that circ-RNF13 and TGIF2 served as competing endogenous RNAs (ceRNAs) for miR-424-5p. Functionally, overexpressing miR-424-5p mimicked and silencing miR-424-5p counteracted the effects of circ-RNF13 depletion in HBV-expressing HCC cells in vitro; TGIF2 restoration partially abrogated the role of miR-424-5p upregulation. In conclusion, circ-RNF13 might sponge miR-424-5p to suppress HBV-associated HCC cells malignant progression and HBV infection by regulating TGIF2, providing a novel insight into the occurrence and treatment of HBV-associated HCC.

Objective: To observe the efficacy of bilateral subthalamic nucleus deep brain stimulation on Pisa syndrome in patients with Parkinson's disease.Methods: A total of 52 patients with Parkinson's disease who underwent deep brain stimulation in Beijing Hospital from July 1, 2016 to July 1, 2020 were reviewed. The clinical data were collected for the patients who met the diagnostic criteria of Pisa syndrome on “Medication-Off” state pre-operatively.Results: Two patients met the diagnostic criteria of Pisa syndrome before operation, with a Pisa angle of 10 and 14°, respectively. The lateral trunk flexion of the two patients improved after operation. In stimulation-on/medication-off state, the Pisa angle decreased from 10 to 2° and from 14 to 6°, respectively.Conclusion: Bilateral subthalamic nucleus deep brain stimulation might have beneficial effects on lateral trunk flexion in PD patients, but the predictors of curative effect are not clear.

To combat global warming, as an energy-saving technology, membrane separation can be applied to capture CO2 from flue gas. Metal–organic frameworks (MOFs) with characteristics like high porosity have great potential as membrane materials for gas mixture separation. In this work, through a combination of grand canonical Monte Carlo and molecular dynamics simulations, the permeability of three gases (CO2, N2, and O2) was calculated and estimated in 6013 computation–ready experimental MOF membranes (CoRE–MOFMs). Then, the relationship between structural descriptors and permeance performance, and the importance of available permeance area to permeance performance of gas molecules with smaller kinetic diameters were found by univariate analysis. Furthermore, comparing the prediction accuracy of seven classification machine learning algorithms, XGBoost was selected to analyze the order of importance of six structural descriptors to permeance performance, through which the conclusion of the univariate analysis was demonstrated one more time. Finally, seven promising CoRE-MOFMs were selected, and their structural characteristics were analyzed. This work provides explicit directions and powerful guidelines to experimenters to accelerate the research on membrane separation for the purification of flue gas.

Background: This study aimed to evaluate the total cerebral small vessel disease (CSVD) score in patients with Parkinson’s disease (PD) at different stages and related factors.Methods: A 100 and seven patients with idiopathic PD and 62 normal controls (NCs) who underwent brain magnetic resonance imaging (MRI) were enrolled. PD patients were divided into two groups: early PD [(Hoehn and Yahr (H&Y) 1–1.5, n = 36)] and advanced PD (H&Y 2–4, n = 71) groups. We calculated the total CSVD score for each participant based on lacunes, high-grade white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS), and cerebral microbleeds (CMBs). Differences in total CSVD score between the PD and NCs and between the two subgroups were compared. In addition, a multivariate logistic regression analysis was conducted to investigate the association between CSVD markers and clinical variables in PD.Results: Lacunes were found in 9.3% of patients with PD, periventricular WMH (PVWMH) in 89.7%, deep WMH (DWMH) in 81.3%, EPVS in 85%, and CMBs in 2.8%. Compared with NCs, patients with PD showed higher PVWMH and DWMH scores. Advanced PD patients exhibited greater PVWMH (P = 0.041), DWMH (P = 0.046), and total CSVD score (P = 0.044) than the early PD group. After adjusting for multiple variables, higher H&Y stage was independently correlated with increased total CSVD score (OR = 2.667, 95% CI 1.154–2.266) and PVWMH score (OR = 2.237, 95% CI 1.084–1.696).Conclusions: CSVD may play a critical role in patients with PD. The total CSVD score is a potential neuroimaging marker for monitoring the progression of PD.

Objectives: The purpose of this study was to evaluate the feasibility and whether synthetic MRI can benefit diagnosis of Alzheimer’s disease (AD).Materials and Methods: Eighteen patients and eighteen age-matched normal controls (NCs) underwent MR examination. The mini-mental state examination (MMSE) scores were obtained from all patients. The whole brain volumetric characteristics, T1, T2, and proton density (PD) values of different cortical and subcortical regions were obtained. The volumetric characteristics and brain regional relaxation values between AD patients and NCs were compared using independent-samples t-test. The correlations between these quantitative parameters and MMSE score were assessed by the Pearson correlation in AD patients.Results: Although the larger volume of cerebrospinal fluid (CSF), lower brain parenchymal volume (BPV), and the ratio of brain parenchymal volume to intracranial volume (BPV/ICV) were found in AD patients compared with NCs, there were no significant differences (p > 0.05). T1 values of right insula cortex and T2 values of left hippocampus and right insula cortex were significantly higher in AD patients than in NCs, but T1 values of left caudate showed a reverse trend (p < 0.05). As the MMSE score decreased in AD patients, the BPV and BPV/ICV decreased, while the volume of CSF and T1 values of bilateral insula cortex and bilateral hippocampus as well as T2 values of bilateral hippocampus increased (p < 0.05).Conclusion: Synthetic MRI not only provides more information to differentiate AD patients from normal controls, but also reflects the disease severity of AD.

A large number of EGFR mutant non‐small cell lung cancer patients primordially benefit from first‐line treatment with first‐generation EGFR‐tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. However, multiple acquired resistance mechanisms have been described that limit the clinical efficacy of first‐generation EGFR‐TKIs. Herein, we report a rare case of lung adenocarcinoma harboring an EGFR exon 19‐deletion mutation before the administration of target therapy. This patient acquired resistance to first‐generation EGFR‐TKIs through small cell lung cancer (SCLC) transformation accompanied by the T790M mutation. Unexpectedly, this SCLC patient maintained a sensitive response to the third‐generation EGFR‐TKI osimertinib. This special case may indicate that osimertinib represents an effective target drug for SCLC patients who harbor an EGFR T790M mutation.

Abstract Background Circulating tumor cells (CTC) shows great prospect to realize precision medicine in cancer patients. Methods We developed the NanoVelcro Chip integrating three functional mechanisms. NanoVelcro CTC capture efficiency was tested in stage III or IV lung adenocarcinoma. Further, ALK-rearrangement status was examined through fluorescent in situ hybridization in CTCs enriched by NanoVelcro. Results NanoVelcro system showed higher CTC-capture efficiency than CellSearch in stage III or IV lung adenocarcinoma. CTC counts obtained by both methods were positively correlated (r = 0.45, p