A nigroincertal projection mediates aversion and enhances coping responses to potential threat.

Recent studies have shown that the non-DA neurons in the ventral tegmental area (VTA) and substantia nigra (SN) not only modulate motivational behaviors but also regulate defensive behaviors. While zona incerta (ZI) is a threat-responsive substrate and receives innervations from the ventral midbrain, the function of the ventral midbrain-to-ZI connection remains poorly defined. Here, we demonstrate that the ZI receives heterogenous innervations from the ventral midbrain. By utilizing a retrograde AAV preferentially labeling non-DA neurons in the ventral midbrain, we found that ZI-projecting non-DA cells in the ventral midbrain are activated by restraint stress. We focused on the SN and found that SN-to-ZI GABAergic input is engaged by a predatory odor. Sustained pan-neuronal SN-to-ZI activation results in aversion and enhances defensive behaviors, likely through a disinhibition mechanism to recruit downstream brain regions that regulate defensive behaviors. Collectively, our results reveal a novel role of nigroincertal projection in mediating negative valence and regulating defensive behaviors.

Computational Insights into SARS-CoV-2 Main Protease Mutations and Nirmatrelvir Efficacy: The Effects of P132H and P132H-A173V.

Nirmatrelvir, a pivotal component of the oral antiviral Paxlovid for COVID-19, targets the SARS-CoV-2 main protease (Mpro) as a covalent inhibitor. Here, we employed combined computational methods to explore how the prevalent Omicron variant mutation P132H, alone and in combination with A173V (P132H-A173V), affects nirmatrelvir's efficacy. Our findings suggest that P132H enhances the noncovalent binding affinity of Mpro for nirmatrelvir, whereas P132H-A173V diminishes it. Although both mutants catalyze the rate-limiting step more efficiently than the wild-type (WT) Mpro, P132H slows the overall rate of covalent bond formation, whereas P132H-A173V accelerates it. Comprehensive analysis of noncovalent and covalent contributions to the overall binding free energy of the covalent complex suggests that P132H likely enhances Mpro sensitivity to nirmatrelvir, while P132H-A173V may confer resistance. Per-residue decompositions of the binding and activation free energies pinpoint key residues that significantly affect the binding affinity and reaction rates, revealing how the mutations modulate these effects. The mutation-induced conformational perturbations alter drug-protein local contact intensities and the electrostatic preorganization of the protein, affecting noncovalent binding affinity and the stability of key reaction states, respectively. Our findings inform the mechanisms of nirmatrelvir resistance and sensitivity, facilitating improved drug design and the detection of resistant strains.

Effects of a 12-week exercise-based intervention on weight management in overweight or obese breast cancer survivors: a randomized controlled trial.

PURPOSE: Breast cancer survivors face dual challenges: long-term sequelae of treatment and the risk of recurrent disease. Furthermore, obesity and a sedentary lifestyle can complicate both challenges. We aimed to assess the effect of a 12-week exercise-based weight-management program in overweight/obese breast cancer survivors. METHODS: A two-arm, single-blinded, randomized controlled trial was conducted among 60 overweight/obese, stage 0-III breast cancer survivors. During the 12-week program, the intervention group received weekly information support, fortnightly exercise prescriptions, including aerobic and resistance exercises to perform at home, and one dietary instruction. The control group received information support about weight management and exercise. Weight, body composition, and physical fitness data were collected at baseline, postintervention, and the 3-month follow-up. RESULTS: The intervention group showed significant improvements in body weight and all adiposity indices, including body mass index, waist circumference, and %body fat, in comparison with baseline (P < 0.001) and the control group (P < 0.05). Both groups showed no significant changes in fat-free mass during the 6-month period (P > 0.05). International Physical Activity Questionnaire scores and left grip strength increased significantly in the intervention group in comparison with the baseline (P < 0.01) and the control group (P < 0.05). Right grip strength, lower-body strength, and aerobic endurance showed no significant intergroup differences (P > 0.05). CONCLUSIONS: A combination of exercise prescription and weight-loss interventions yielded clinically meaningful weight loss in overweight/obese breast cancer survivors. These findings may facilitate the incorporation of home-based exercise and weight management into breast cancer treatment and survivorship care.

Unveiling adcyap1 as a protective factor linking pain and nerve regeneration through single-cell RNA sequencing of rat dorsal root ganglion neurons.

BACKGROUND: Severe peripheral nerve injury (PNI) often leads to significant movement disorders and intractable pain. Therefore, promoting nerve regeneration while avoiding neuropathic pain is crucial for the clinical treatment of PNI patients. However, established animal models for peripheral neuropathy fail to accurately recapitulate the clinical features of PNI. Additionally, researchers usually investigate neuropathic pain and axonal regeneration separately, leaving the intrinsic relationship between the development of neuropathic pain and nerve regeneration after PNI unclear. To explore the underlying connections between pain and regeneration after PNI and provide potential molecular targets, we performed single-cell RNA sequencing and functional verification in an established rat model, allowing simultaneous study of the neuropathic pain and axonal regeneration after PNI. RESULTS: First, a novel rat model named spared nerve crush (SNC) was created. In this model, two branches of the sciatic nerve were crushed, but the epineurium remained unsevered. This model successfully recapitulated both neuropathic pain and axonal regeneration after PNI, allowing for the study of the intrinsic link between these two crucial biological processes. Dorsal root ganglions (DRGs) from SNC and naïve rats at various time points after SNC were collected for single-cell RNA sequencing (scRNA-seq). After matching all scRNA-seq data to the 7 known DRG types, we discovered that the PEP1 and PEP3 DRG neuron subtypes increased in crushed and uncrushed DRG separately after SNC. Using experimental design scRNA-seq processing (EDSSP), we identified Adcyap1 as a potential gene contributing to both pain and nerve regeneration. Indeed, repeated intrathecal administration of PACAP38 mitigated pain and facilitated axonal regeneration, while Adcyap1 siRNA or PACAP6-38, an antagonist of PAC1R (a receptor of PACAP38) led to both mechanical hyperalgesia and delayed DRG axon regeneration in SNC rats. Moreover, these effects can be reversed by repeated intrathecal administration of PACAP38 in the acute phase but not the late phase after PNI, resulting in alleviated pain and promoted axonal regeneration. CONCLUSIONS: Our study reveals that Adcyap1 is an intrinsic protective factor linking neuropathic pain and axonal regeneration following PNI. This finding provides new potential targets and strategies for early therapeutic intervention of PNI.

Polarization-insensitive phase-modulated metasurface using single thermally stimulated vanadium dioxide chip.

Considering that typically more than two pin diodes or other tunable elements are required in the unit cell of polarization-insensitive reconfigurable metasurfaces (RMs), this paper proposes a new approach to design a polarization-insensitive RM unit using only one VO2 chip. A polarization-insensitive phase-modulated metasurface (PMM) using single VO2 chip is presented. The surface layer is composed of an outer ring and an inner cross, with a VO2 chip loaded at the connection of the cross. As the VO2 chip can be connected with the metal patch on all sides, only one VO2 chip is used in this polarization-insensitive design. By thermally controlling VO2 chips switch between low-resistance and high-resistance states, the PMM achieves a 1-bit phase shift within 180° ± 37° from 7.85 to 15 GHz. A prototype is fabricated and measured, and the measured results have verified the correction of the design and analysis of the designed PMM.

Sex- and age-specific prevalence and risk factors of depressive symptoms in Parkinson's disease.

Although depressive symptoms are common in PD, few studies investigated sex and age differences in depressive symptoms. Our study aimed to explore the sex and age differences in the clinical correlates of depressive symptoms in patients with PD. 210 PD patients aged 50-80 were recruited. Levels of glucose and lipid profiles were measured. The Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MoCA) and the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) assessed depressive symptom, cognition and motor function, respectively. Male depressive PD participants had higher fasting plasma glucose (FPG) levels. Regarding the 50-59 years group, depressive patients had higher TG levels. Moreover, there were sex and age differences in the factors associated with severity of depressive symptoms. In male PD patients, FPG was an independent contributor to HAMD-17 (Beta = 0.412, t = 4.118, p < 0.001), and UPDRS-III score was still associated with HAMD-17 in female patients after controlling for confounding factors (Beta = 0.304, t = 2.961, p = 0.004). Regarding the different age groups, UPDRS-III (Beta = 0.426, t = 2.986, p = 0.005) and TG (Beta = 0.366, t = 2.561, p = 0.015) were independent contributors to HAMD-17 in PD patients aged 50-59. Furthermore, non-depressive PD patients demonstrated better performance with respect to visuospatial/executive function among the 70-80 years group. These findings suggest that sex and age are crucial non-specific factors to consider when assessing the relationship between glycolipid metabolism, PD-specific factors and depression.

Microbulbifer zhoushanensis sp. nov., Microbulbifer sediminum sp. nov. and Microbulbifer guangxiensis sp. nov., three marine bacteria isolated from a tidal flat.

Three strains, TT30T, TT37T and L3T, were isolated from tidal flat samples. Cells were Gram-stain-negative, non-motile and rod shaped. Cells of strains TT30T and TT37T were able to grow in a medium containing 1.0-15.0 % (w/v) NaCl (optimum, 3.0 and 4.0 %, respectively), and cells of strain L3T was able to grow in a medium containing 1.0-10.0 % (w/v) NaCl (optimum, 1.0 %). Growth of the three strains was observed at pH 6.0-10.0 and at 10-40 °C. Strains TT30T, TT37T and L3T showed the highest similarity to Microbulbifer hydrolyticus DSM 11525T (97.7 %), M. yueqingensis CGMCC 1.10658T (98.0 %) and M. elongatus DSM 6810T (97.9 %), respectively. Results of phylogenetic analyses indicated that the three isolates represented two distinct lineages within the genus Microbulbifer. The DNA G+C contents of strains TT30T, TT37T and L3T were 61.3, 60.9 and 60.2%, respectively. The average nucleotide identity and in silico DNA-DNA hybridization values among strains TT30T, TT37T and L3T and the reference strains were 84.4-87.4 and 19.6-28.9 %, respectively. Differential phenotypic properties, chemotaxonomic differences, phylogenetic distinctiveness, together with the genomic data, demonstrated that strains TT30T, TT37 T and L3T represent novel species of the genus Microbulbifer, which are named Microbulbifer zhoushanensis sp. nov. (TT30T=KCTC 92167T=MCCC 1K07276T), Microbulbifer sediminum sp. nov. (TT37T=KCTC 92168T=MCCC 1K07277T) and Microbulbifer guangxiensis sp. nov. (L3T=KCTC 92165T=MCCC 1K07278T).

Functional characterization and in vitro pharmacological rescue of KCNQ2 pore mutations associated with epileptic encephalopathy.

Mutations in the KCNQ2 gene encoding KV7.2 subunit that mediates neuronal M-current cause a severe form of developmental and epileptic encephalopathy (DEE). Electrophysiological evaluation of KCNQ2 mutations has been proved clinically useful in improving outcome prediction and choosing rational anti-seizure medications (ASMs). In this study we described the clinical characteristics, electrophysiological phenotypes and the in vitro response to KCNQ openers of five KCNQ2 pore mutations (V250A, N258Y, H260P, A265T and G290S) from seven patients diagnosed with KCNQ2-DEE. The KCNQ2 variants were transfected into Chinese hamster ovary (CHO) cells alone, in combination with KCNQ3 (1:1) or with wild-type KCNQ2 (KCNQ2-WT) and KCNQ3 in a ratio of 1:1:2, respectively. Their expression and electrophysiological function were assessed. When transfected alone or in combination with KCNQ3, none of these mutations affected the membrane expression of KCNQ2, but most failed to induce a potassium current except A265T, in which trace currents were observed when co-transfected with KCNQ3. When co-expressed with KCNQ2-WT and KCNQ3 (1:1:2), the currents at 0 mV of these mutations were decreased by 30%-70% compared to the KCNQ2/3 channel, which could be significantly rescued by applying KCNQ openers including the approved antiepileptic drug retigabine (RTG, 10 µM), as well as two candidates subjected to clinical trials, pynegabine (HN37, 1 µM) and XEN1101 (1 µM). These newly identified pathologic variants enrich the KCNQ2-DEE mutation hotspots in the pore-forming domain. This electrophysiological study provides a rational basis for personalized therapy with KCNQ openers in DEE patients carrying loss-of-function (LOF) mutations in KCNQ2.

Temporal and spatial variations of disinfection by-products in South Taihu's drinking water, Zhejiang Province, China.

Some disinfection by-products (DBPs) in drinking water present a potential safety concern. This study focuses on the elements influencing DBPs formation. A total of 120 water samples were collected from 10 different drinking water facilities spanning 5 counties within Huzhou, Zhejiang Province, China. Concentrations of trihalomethanes (THMs) and haloacetic acids (HAAs) were observed to be 14.5 and 27.4 µg/L, respectively, constituting 34 and 64% of the total DBPs. Seasonal fluctuations demonstrated that HAAs, THMs, halonitromethanes (HNMs), and haloacetonitriles (HANs) followed a similar pattern with higher levels in summer or autumn compared to spring. Importantly, the concentrations of HAAs and THMs were markedly higher in Taihu-sourced water compared to other sources. Geographically, Nanxun exhibited the highest levels of total DBPs, HAAs, and THMs, while Deqing and Changxing demonstrated significantly lower levels. Correlation studies between water quality parameters and DBPs revealed that factors such as chloride content, temperature, and residual chlorine positively influenced DBPs formation, whereas turbidity negatively affected it. Principal component analysis suggested similar formation processes for HANs, haloketones (HKs), HNMs, and THMs. Factors such as temperature, chemical oxygen demand (COD), and residual chlorine were identified as significant contributors to the prevalence of HAAs.

Identification of and Mechanistic Insights into SARS-CoV-2 Main Protease Non-Covalent Inhibitors: An In-Silico Study.

The indispensable role of the SARS-CoV-2 main protease (Mpro) in the viral replication cycle and its dissimilarity to human proteases make Mpro a promising drug target. In order to identify the non-covalent Mpro inhibitors, we performed a comprehensive study using a combined computational strategy. We first screened the ZINC purchasable compound database using the pharmacophore model generated from the reference crystal structure of Mpro complexed with the inhibitor ML188. The hit compounds were then filtered by molecular docking and predicted parameters of drug-likeness and pharmacokinetics. The final molecular dynamics (MD) simulations identified three effective candidate inhibitors (ECIs) capable of maintaining binding within the substrate-binding cavity of Mpro. We further performed comparative analyses of the reference and effective complexes in terms of dynamics, thermodynamics, binding free energy (BFE), and interaction energies and modes. The results reveal that, when compared to the inter-molecular electrostatic forces/interactions, the inter-molecular van der Waals (vdW) forces/interactions are far more important in maintaining the association and determining the high affinity. Given the un-favorable effects of the inter-molecular electrostatic interactions-association destabilization by the competitive hydrogen bond (HB) interactions and the reduced binding affinity arising from the un-compensable increase in the electrostatic desolvation penalty-we suggest that enhancing the inter-molecular vdW interactions while avoiding introducing the deeply buried HBs may be a promising strategy in future inhibitor optimization.

Anti-Adhesive Properties of Calcium Alginate from Sargassum fusiforme against Particulate Matter-Induced Inflammation.

Fine dust generated by particulate matter (PM) pollution is a serious ecological issue in industrialized countries and causes disorders of the respiratory system and skin in humans. In the previous study, Sargassum fusiforme was treated with citric acid to remove heavy metals. In this study, the transfer of PM-mediated inflammatory responses through the skin to macrophages was evaluated. Moreover, the anti-adhesive effects of calcium alginate isolated from S. fusiforme (SFCA) against PM-induced inflammation were investigated. The structures of processing and unprocessing SFCA were then analyzed by Fourier-transform infrared spectroscopy (FT-IR), revealing minimal change after acid-processing. SFCA had protective effects both in PM-stimulated HaCaT keratinocytes and RAW 264.7 macrophages. In cellular environments, it was found that SFCA attenuated signal protein expressions such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, prostaglandin E2 (PGE2), and pro-inflammatory cytokines. Furthermore, macrophages were added to the culture medium of PM-stimulated keratinocytes to induce inflammation. SFCA was observed to significantly inhibit inflammatory responses; additionally, SFCA showed an in vivo anti-adhesive effect in zebrafish embryos.

Variances and covariances of linear summary statistics of segregating sites.

Each mutation in a population sample of DNA sequences can be classified by the number of sequences that inherit the mutant nucleotide, the resulting frequencies are known as mutations of different sizes or site frequency spectrum. Many summary statistics can be defined as a linear function of these frequencies. A flexible class of such linear summary statistics is explored analytically in this paper which include several well-known quantities, such as the number of segregating sizes and the mean number of nucleotide differences between two sequences. Some asymptotic variances and covariances are obtained while the analytical formulas for the variances and covariances of nine such linear summary statistics are derived, most of which are unknown to date. This study not only provides some theoretical foundations for exploring linear summary statistics, but also provides some newlinear summary statistics that may be utilized for analyzing sample polymorphism. Furthermore it is showed that a newly developed linear summary statistics has a smaller variance almost uniformly than Watterson's estimator, and that a class of linear summary statistics given too heavy weights on mutations of smaller sizes result in asymptotically non-zero variance.

Amitosis as a strategy of cell division-Insight from the proliferation of Tetrahymena thermophila macronuclei.

Cell division is a necessity of life which can be either mitotic or amitotic. While both are fundamental, amitosis is sometimes considered a relic of little importance in biology. Nevertheless, eukaryotes often have polyploid cells, including cancer cells, which may divide amitotically. To understand how amitosis ensures the completion of cell division, we turn to the macronuclei of ciliates. The grand scheme governing the proliferation of the macronuclei of ciliate cells, which involves chromosomal replication and amitosis, is currently unknown, which is crucial for developing population genetics model of ciliate populations. Using a novel model that encompasses a wide range of mechanisms together with experimental data of the composition of mating types at different stages derived from a single karyonide of Tetrahymena thermophila, we show that the chromosomal replication of the macronucleus has a strong head-start effect, with only about five copies of chromosomes replicated at a time and persistent reuse of the chromosomes involved in the early replication. Furthermore the fission of a fully grown macronucleus is non-random with regard to chromosome composition, with a strong tendency to push chromosomes and their replications to the same daughter cell.

Cognition, motor symptoms, and glycolipid metabolism in Parkinson's disease with depressive symptoms.

Depressive symptoms and abnormal glycolipid metabolisms are common in patients with Parkinson's disease (PD), but their relationship has not been fully reported. It is not clear whether glycolipid impairments lead to poor cognitive and motor function, and aggravate depressive symptoms. Therefore, we aimed to explore the relationships between glycolipid variables, cognition, motor and depressive symptoms in PD patients cross-sectionally. Two hundred ten PD patients were recruited. Glycolipid parameters and Uric acid (UA) were measured. Depressive symptoms, cognitive function and motor symptoms were assessed using the Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MOCA) and the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part-III (UPDRS-III). Depressive PD patients had significantly worse motor symptoms and higher levels of fasting plasma glucose (FPG) than those in non-depressive patients (F = 24.145, P < 0.001). Further, logistic regression analysis indicated that UPDRS-III (OR = 1.039, 95% CI 1.019-1.057, P = 0.044), FPG (OR = 1.447, 95% CI 1.050-1.994, P = 0.024) were independently associated with depression. In PD patients without depression, UA (ß = - 0.068, t = - 2.913, P = 0.005) and cholesterol (CHOL) (ß = - 3.941, t = - 2.518, P = 0.014) were independent predictors of the UPDRS-III score; in addition, UPDRS-III score was negatively associated with MOCA score (ß = - 0.092, t = - 2.791, P = 0.007). FPG levels and motor symptoms were related to depressive symptoms in PD patients. Further, in non-depressive PD patients, UA and CHOL showed putative biomarkers of motor symptoms.

Glycopolymer Nanoparticles with On-Demand Glucose-Responsive Insulin Delivery and Low-Hypoglycemia Risks for Type 1 Diabetic Treatment.

Diabetic patients with type 1 or advanced type 2 stages need timely and precise insulin injection to regulate the daily blood glucose levels (BGLs). Otherwise, risks of serious or even deadly diabetes-associated complications occur. To achieve prolonged glucose regulation and low hypoglycemia risks, a novel on-demand glucose-responsive glycopolymer system was constructed for insulin delivery, which was self-assembled into nanoparticles by dynamic covalent bonds between two polymers: fluorophenylboronic acid-grafted polymer (poly-F) and polyol polymer (poly-G). Insulin was loaded during the assembly process. The nanoparticles showed excellent glucose responsiveness in vitro, with controlled insulin release at different glucose concentrations. In vivo treatment on type 1 diabetic mice showed prolonged BGL regulation and lower hypoglycemia risks. The mild preparation of the nanoparticles and outstanding glucose control shed light on the optional diabetic treatment for further clinical use.

NIR Activated Upper Critical Solution Temperature Polymeric Micelles for Trimodal Combinational Cancer Therapy.

The balance between drug efficiency and its side effects on normal tissues is still a challenging problem to be solved in current cancer therapies. Among different strategies, cancer therapeutic methods based on nanomedicine delivery systems have received extensive attention due to their unique advantages such as improved circulation and reduced toxicity of drugs in the body. Herein, we constructed dual-responsive polymeric micelles DOX&ALS@MFM based on an upper critical solution temperature (UCST) polymer to simultaneously combine chemotherapy, photothermal therapy (PTT), and photodynamic therapy (PDT). Amphiphilic block copolymer P(AAm-co-AN)-b-PEI-ss-PEG-FA with a critical point of 42 °C was able to self-assemble into polymeric micelles under physiological conditions, which further encapsulated anticancer drug doxorubicin (DOX) and photosensitizer ALS to obtain drug-loaded micelles DOX&ALS@MFM. Micelles aggregated at tumor sites due to folate targeting and an enhanced permeability retention (EPR) effect. After that, the high intracellular concentration of glutathione (GSH) and near-infrared (NIR) light prompted disassembly of the polymer to release DOX and ALS. ALS not only plays a role in PTT but also produces singlet oxygen, therefore killing tumor cells by PDT. Both in vitro and in vivo studies demonstrated the photothermal conversion and reactive oxygen species generation ability of DOX&ALS@MFM micelles, at the same time as the excellent inhibitory effect on tumor growth with NIR light irradiation. Thus, our research substantiated a new strategy for the biomedical application of UCST polymers in the cited triple modal tumor therapy.

Direct C(sp3)-H Polyfluoroarylation: Access to Polyfluoroaryl Amino Acids via Rh-Catalyzed Selective C-F Bond Cleavage.

A catalytic selective C-F bond alkylation method for polyfluoroarene with glycinates and derivatives in the presence of a DavePhos-ligated Rh catalyst was developed. This method avoids the preactivation of alkylating reagents and provides an efficient and straightforward route to synthesize a series of polyfluoroaryl amino acids via C(sp3)-H functionalization. This reaction proceeds under mild conditions and exhibits high reactivity and excellent chemoselectivities. Meanwhile, the synthetic potential of this method was demonstrated by gram-scale synthesis, and further transformations proved the application value of the products as well.

Size Effect of Arylenediimide π-Conjugate Systems on the Photoresponsive Behaviors in Eu3+-Based Coordination Polymers.

Various arylenediimides (ADIs) have been applied to construct photoresponsive coordination polymers (CPs), while the size effect of ADI π-conjugate systems on the photoresponsive behaviors in CPs has been overlooked in the past few years. Herein, we emphasize the size effect of ADI π-conjugate systems on photoinduced electron transfer (ET) in CPs, taking two Eu3+-based CPs, [Eu(H2BINDI)(BINDI)0.5(H2O)2]·NH2(CH3)2·8H2O (1) and [Eu2(BIPMDI)(DMF)4(NO3)2]·H2O·2DMF (2) [H4BINDI = N,N'-bis(5-isophthalic acid)naphthalenediimide; H4BIPMDI = N,N'-bis(5-isophthalic acid)pyromellitic diimide; DMF = N,N-dimethylformamide], as a case. Both 1 and 2 display ET-based photochromic behaviors with distinct photoresponsive rates and coloration contrast, which can contribute to the size effect of diimide cores on the interfacial contacts of electron donors/acceptors. Meanwhile, ET between the neighboring larger NDI cores of the H4BINDI ligands can block ligand-to-metal charge transfer and quench luminescence of the Eu3+ metal center in 1. Therefore, this work will provide a theoretical basis for the development and exploration of photoresponsive materials.

Global research trends of immunotherapy and biotherapy for inflammatory bowel disease: a bibliometric analysis from 2002 to 2021.

BACKGROUND: It is known that inflammatory bowel disease is the result of a defective immune system, and immunotherapy and biological therapy have gradually become important means to treat it. This paper focused on the bibliometric statistical analysis of the current research progress to summarize the research status of this field and analyze the research trends in recent years. METHODS: Two visualization tools, CiteSpace and VOSviewer, were used to explore the data of journals, institutions, countries/regions, authors, references, and keywords for the literature included in the Web of Science Core Collection from January 1, 2002, to December 31, 2021. RESULTS: A total of 312 papers were published in 120 journals by 603 institutions from 40 countries/regions, with 9463 co-cited references. The United States has the most publications with the highest total citations in the world. Inflammatory Bowel Diseases published the maximum number of papers, and Gastroenterology devoted the most co-citations to immunotherapy and biological therapy for IBD. In addition, we found that the studies before 2009 mostly focused on clinical trials while researchers have paid more attention to clinical management in therapy for IBD since 2009. Combination therapy and management of the treatment for the disease have become research hotspots. CONCLUSION: The focus of immunotherapy and biotherapy for IBD has shifted from clinical trials to the management of the risks and benefits of immunotherapy.

Differential associations between simple physical performance tests with global and specific cognitive functions in cognitively normal and mild cognitive impairment: a cross-sectional cohort study of Asian community-dwelling older adults.

BACKGROUND: Physical performance declines and executive dysfunctions are predictors of dementia. However, their associations are not well understood in Asian older adults without dementia (cognitively normal [CN] and mild cognitive impairment [MCI]), especially in a single study. OBJECTIVE: Examine the associations between physical performance measures with executive function (EF)-based and non-EF-based neurocognitive tests and whether preclinical dementia cognitive status i.e., CN and MCI, moderated these associations. METHODS: We examined cross-sectional cohort of 716 community-dwelling older adults without dementia (CN = 562 and MCI = 154) using multivariable linear regression models. We associated three simple physical performance measures, namely timed-up-and-go (TUG), fast gait speed (FGS), and 30-s chair stand test (30 s-CST), with a comprehensive neurocognitive test battery measuring EF and non-EF cognitive functions. Moderating effects of cognitive status on the associations were examined. In all models, we controlled for pertinent covariates, including age, education, medical and psychiatric status. RESULTS: Upon controlling for covariates, TUG was most strongly and positively associated with multiple EF-based neurocognitive tests, followed by FGS, with 30 s-CST having the weakest associations. For all physical performance measures, no significant associations with non-EF-based neurocognitive tests were detected. Cognitive status significantly moderated the associations between all physical measures and several neurocognitive tests, with stronger associations in the MCI than CN. CONCLUSION: Compared to FGS and 30 s-CST, TUG had the most robust associations with multiple EF-based cognitive functions. Given their differential associations with global and detailed neurocognitive tests and significant moderating effects of cognitive status, findings highlight a need to carefully consider the choices of simple physical performance tests when using these tests with a heterogenous group of community-dwelling older adults without dementia.