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The indications for percutaneous kyphoplasty (PKP) and percutaneous vertebroplasty (PVP) are painful vertebral compression fractures. Our study is to assess the risk–benefit ratio of PKP/PVP surgery in the patients with newly diagnosed multiple myeloma (NDMM) without receiving antimyeloma therapy. The clinical data of 426 consecutive patients with NDMM admitted to our center from February 2012 to April 2022 were retrospectively analyzed. The baseline data, postoperative pain relief, the proportion of recurrent vertebral fractures, and survival time were compared between the PKP/PVP surgical group and the nonsurgical group in the NDMM patients. Of the 426 patients with NDMM, 206 patients had vertebral fractures (206/426, 48.4%). Of these, 32 (32/206, 15.5%) underwent PKP/PVP surgery for misdiagnosis of simple osteoporosis prior to diagnosis of MM (surgical group), and the other 174 (174/206, 84.5%) did not undergo surgical treatment prior to definitive diagnosis of MM (non-surgical group). The median age of patients in the surgical and nonsurgical groups was 66 and 62 years, respectively (p = 0.01). The proportion of patients with advanced ISS and RISS stages was higher in the surgical group (ISS stage II + III 96.9% vs. 71.8%, p = 0.03; RISS stage III 96.9% vs. 71%, p = 0.01). Postoperatively, 10 patients (31.3%) never experienced pain relief and 20 patients (62.5%) experienced short-term pain relief with a median duration of relief of 2.6 months (0.2–24.1 months). Postoperative fractures of vertebrae other than the surgical site occurred in 24 patients (75%) in the surgical group, with a median time of 4.4 months postoperatively (0.4–86.8 months). Vertebral fractures other than the fracture site at the first visit occurred in 5 patients (2.9%) in the nonoperative group at the time of diagnosis of MM, with a median time of 11.9 months after the first visit (3.5–12.6 months). The incidence of secondary fractures was significantly higher in the surgical group than in the nonsurgical group (75% vs. 2.9%, p = 0.001). The time interval between the first visit and definitive diagnosis of MM was longer in the surgical group than in the nonsurgical group (6.1 months vs. 1.6 months, p = 0.01). At a median follow-up of 32 months (0.3–123 months), median overall survival (OS) was significantly shorter in the surgical group than in the nonsurgical group (48.2 months vs. 66 months, p = 0.04). Application of PKP/PVP surgery for pain relief in NDMM patients without antimyeloma therapy has a limited effect and a high risk of new vertebral fractures after surgery. Therefore, patients with NDMM may need to have their disease controlled with antimyeloma therapy prior to any consideration for PKP/PVP surgery.

Aims Members of the chromogranin family play a role in angiogenesis. One such biologically active peptide, generated through the processing of chromogranin A, is vasostatin-2. This study aimed at assessing the association of serum vasostatin-2 levels with coronary collateral vessels (CCV) in diabetic patients with chronic total occlusions (CTO) and the effects of vasostatin-2 on angiogenesis in diabetic mice with hindlimb or myocardial ischemia. Methods and results Serum levels of vasostatin-2 in 452 diabetic CTO patients were evaluated. The status of CCV was categorized according to the Rentrop score. Vasostatin-2 recombinant protein or phosphate-buffered saline were then injected intraperitoneally in diabetic mouse models of hindlimb or myocardial ischemia, followed by laser Doppler imaging and molecular biology examinations. The effects of vasostatin-2 were also ascertained in endothelial cells and macrophages, with mechanisms clarified using ribonucleic acid (RNA) sequencing. Serum levels of vasostatin-2 were significantly different and progressively higher across Rentrop score 0, 1, 2, and 3 groups (P < .001), with significantly lower levels in patients with poor CCV (Rentrop score 0 and 1) than in those with good CCV (Rentrop score 2 and 3) (P < .05). Vasostatin-2 significantly promoted angiogenesis in diabetic mice with hindlimb or myocardial ischemia. RNA-seq analyzes verified an angiotensin-converting enzyme 2 (ACE2)-mediated vasostatin-2-induction of angiogenesis in ischemic tissues. Conclusion Lower serum levels of vasostatin-2 are associated with poor CCV in diabetic CTO patients compared with patients with good CCV. Vasostatin-2 significantly promotes angiogenesis in diabetic mice with hindlimb or myocardial ischemia. Such effects are mediated by ACE2.

A water soluble macrocyclic arene 1 was synthesized and found that it could form a 1 : 1 complex with N-methylquinolinium salts in water. The complexation and decomplexation of the complexes could be achieved by changing the pH of the solution.

An AIE-active Schiff base was available for indicator paper and cell imaging applications for the successive identification of Cu2+ and His.

An Ag/Cr/MnO2 catalyst was prepared via a simple hydrothermal–calcination method. Compared with the Cr/MnO2 catalyst, the comprehensive performance of the Ag/Cr/MnO2 catalyst was greatly improved, which has potential for industrial applications.

A new hybrid uranyl-silicotungstate (U3) was synthesized and characterized. U3 contains two kinds of Keggin-type building units and shows good catalytic activity in the synthesis of dihydropyrimidin-2(1H)-ones from aldehydes, acetoacetates, and urea.

Due to advances in medical treatments, a substantial proportion of heart failure (HF) patients with reduced left ventricular ejection fraction (EF, HFrEF) have experienced partial or complete recovery of EF, termed HFrecEF, and markedly improved clinical outcomes. In the present study, we sought to investigate the relationship between glycemic control and the incidence of HFrecEF in hospitalized HFrEF patients with type 2 diabetes mellitus (T2DM).A total of 463 hospitalized T2DM patients with HFrEF were consecutively enrolled. Follow-up echocardiogram was performed after around 12 months. Patients who had an absolute EF improvement ≥10% and a second EF 40% were classified into HFrecEF, and those who did not meet these criteria were defined as persistent HFrEF.During the 12-month follow-up, 44.5% of T2DM patients developed HFrecEF. Patients with HFrecEF had significantly lower HbA1c level than those with persistent HFrEF (6.5% [IQR 5.8% ∼ 7.2%] vs. 6.7% [IQR 6.1% ∼ 7.8%], P = 0.003), especially in HF of an ischemic etiology. HbA1c levels were inversely correlated with changes in EF during follow-up. After multivariate adjustment, every 1% increase in HbA1c conferred a 17.4% (OR: 0.826 [95% CI 0.701-0.968]) lower likelihood of HFrecEF. Compared to patients with good glycemic control (HbA1c ≤ 6.2%), those with poor glycemic control (HbA1c 7.1%) had a 52.0% (OR: 0.480 [95% CI 0.281-0.811] decreased likelihood of HFrecEF.This study demonstrates that uncontrolled HbA1c level is associated with compromised development of HFrecEF in T2DM patients with HF, especially in those with an ischemic etiology.

To screen coral-derived compounds with neuroprotective activity and clarify the potential mechanism of lead compounds.The lead compounds with neuroprotective effects were screened by HThree compounds (No. 63, 68, and 74), derived from marine corals, could markedly alleviate the cell damage and notably reverse the loss of worm dopaminergic neurons. Further investigation indicated that compound 63 could promote the expression of Nurr1 and inhibit neuronal apoptosis signaling pathways.Lead compounds from marine corals exerted significant neuroprotective effects， which indicated that coral might be a new and potential resource for screening and isolating novel natural compounds with neuroprotective effects. Furthermore, this study also provided a new strategy for the clinical treatment of neurodegenerative diseases such as Parkinson's disease.

It is a great challenge for the rational molecular design of light-emitting conjugated polymers to inherently suppress the ubiquitous coffee-ring effect (CRE), which is the critical bottleneck for ...

An efficient copper nitrate mediated difunctionalization of alkenes with N-fluorobenzenesulfonimide (NFSI) has been developed for the direct synthesis of β-aminonitrates in moderate to excellent yields with high regioselectivity. This reaction proceeds through a radical process, where copper nitrate is used as the nitrate source and NFSI as the nitrogen source. The given protocol provides a direct access to functionalized nitrates with operational simplicity, good functional group tolerance, and a wide substrate scope. The reaction can be performed on a gram scale and the synthetic utility of the product is demonstrated.

PurposeTechnostress is becoming one of the main challenges among employees in the increasingly digital work context. Following the job demands-resources (JD-R) theory, this study aims to understand how technostress (e.g. techno-overload, techno-complexity, techno-insecurity and techno-uncertainty) decreases employees’ work well-being through exhausting one’s emotional and physical resources (i.e. work exhaustion), and to what extent workplace knowledge diversity could buffer this relationship.Design/methodology/approachThe authors collected three-wave data of 235 employees from three manufacturing companies in China. They conducted a moderated mediation model to test their hypotheses.FindingsThe results showed that work exhaustion mediated the relationship between technostress and employee work well-being and that perceived workplace knowledge diversity buffered this indirect effect.Originality/valueThis study might be one of the first attempts using the JD-R theory together with a three-wave longitudinal survey design to empirically examine the mediating role of work exhaustion and the moderating role of workplace knowledge diversity. The authors contribute to the information and technology management literature by underscoring the importance of being aware of technostress and managing technology-induced work exhaustion. They highlight that a knowledge-diverse work environment is an essential context that can help employees to handle difficult and complex tasks presented by various technologies and alleviate experienced technostress.

Metastasis, in which cancer cells detach from the original site and colonise other organs, is the primary cause of death induced by bladder cancer (BCa). Epithelial Membrane Protein 1 (EMP1) is dysregulated in many human cancers, and its clinical significance and biological function in diseases, including BCa, are largely unclear. Here, we demonstrated that EMP1 was downregulated in BCa cells. The deficiency of EMP1 promotes migration and confers resistance to ferroptosis/oxidative stress in BCa cells, favouring tumour cell metastasis. Mechanistically, we demonstrated that EMP1 deficiency enhanced tumour metastasis by increasing PPARG expression and promoting its activation, leading to upregulation of pFAK(Y397) and SLC7A11, which promoted cell migration and anti-ferroptotic cell death respectively. Moreover, we found EMP1-deficient sensitized cells to PPARG's ligand, which effect are metastatic phenotype promoted and could be mitigated by FABP4 knockdown. In conclusion, our study, for the first time, reveals that EMP1 deficiency promotes BCa cell migration and confers resistance to ferroptosis/oxidative stress, thus promoting metastasis of BCa via PPARG. These results revealed a novel role of EMP1-mediated PPARG in bladder cancer metastasis.

The X2-mode electron cyclotron heating (ECH) assisted start-up has been studied experimentally on the J-TEXT device to determine the minimum ECH power requirements to assist breakdown and develop a better physics description of the process. Results indicate that the minimum toroidal electric field for a successful start-up on J-TEXT was expanded from 2.5 V m−1 to 0.56 V m−1, and that injecting 300 kW of X2-mode ECH power can ensure robust breakdown. The critical ECH power for successful start-up was determined to be approximately 200 kW. At lower powers ECH was observed to cause ionization but this did not necessarily result in successful start-up. The effects of varying ECH power, pulse-width and toroidal magnetic field on start-up were also investigated. Higher ECH power leads to quicker, stronger ionization and CIII emission, and is beneficial for burn-through. Higher pre-plasma density caused by high ECH power can decrease the required toroidal electric field for the Ohmic breakdown, while the enhanced CIII emission may be not good for the startup. The characteristics of the pre-plasma formed by ECH prior to the application of the loop voltage were also studied. The toroidal magnetic field affects the initial location where pre-plasma forms and this also affected the subsequent tokamak startup. The analysis of spatial density showed that the pre-plasma can radially develop at a velocity of 600 m s−1. Furthermore, it was found that injecting ECH power at the appropriate time with a low power of 150 kW can achieve similar pre-ionization results as the high power case. The transition from ECH plasma to Ohmic plasma suggests that the ECH assisted start-up modified the process of purely Ohmic breakdown.

Alumina is the most promising ceramic armor material and SHPB testing is typically used to investigate dynamic deformation behaviour and ballistic mechanisms. In this research the effect of the incident wave shaping technique on the stress equilibrium state during testing was analysed. The compressive strength of alumina ceramic materials was evaluated under high strain rate compressive loads of 1200-1800/s. The SHPB compression strength was found to increase with decreasing grain size to a maximum of 3.80±0.25 GPa, and the ceramic materials studied exhibited high strain-rate sensitive mechanical properties due to crack tip inertia effects.

Supplementary Figure from Human Colon Cancer–Derived Clostridioides difficile Strains Drive Colonic Tumorigenesis in Mice

Supplementary Table from Human Colon Cancer–Derived Clostridioides difficile Strains Drive Colonic Tumorigenesis in Mice

Defining the complex role of the microbiome in colorectal cancer and the discovery of novel, protumorigenic microbes are areas of active investigation. In the present study, culturing and reassociation experiments revealed that toxigenic strains of Clostridioides difficile drove the tumorigenic phenotype of a subset of colorectal cancer patient–derived mucosal slurries in germ-free ApcMin/+ mice. Tumorigenesis was dependent on the C. difficile toxin TcdB and was associated with induction of Wnt signaling, reactive oxygen species, and protumorigenic mucosal immune responses marked by the infiltration of activated myeloid cells and IL17-producing lymphoid and innate lymphoid cell subsets. These findings suggest that chronic colonization with toxigenic C. difficile is a potential driver of colorectal cancer in patients.Significance:Colorectal cancer is a leading cause of cancer and cancer-related deaths worldwide, with a multifactorial etiology that likely includes procarcinogenic bacteria. Using human colon cancer specimens, culturing, and murine models, we demonstrate that chronic infection with the enteric pathogen C. difficile is a previously unrecognized contributor to colonic tumorigenesis.See related commentary by Jain and Dudeja, p. 1838.This article is highlighted in the In This Issue feature, p. 1825

Chronic and low-grade inflammation associated with persistent bacterial infections has been linked to colon tumor development; however, the impact of transient and self-limited infections in bacterially driven colon tumorigenesis has remained enigmatic. Here we report that UshA is a novel genotoxin in attaching/effacing (A/E) pathogens, which include the human pathogens enteropathogenic Escherichia coli, enterohemorrhagic E. coli, and their murine equivalent Citrobacter rodentium (CR). UshA harbors direct DNA digestion activity with a catalytic histidine–aspartic acid dyad. Injected via the type III secretion system (T3SS) into host cells, UshA triggers DNA damage and initiates tumorigenic transformation during infections in vitro and in vivo. Moreover, UshA plays an indispensable role in CR infection–accelerated colon tumorigenesis in genetically susceptible ApcMinΔ716/+ mice. Collectively, our results reveal that UshA, functioning as a bacterial T3SS-dependent genotoxin, plays a critical role in prompting transient and noninvasive bacterial infection–accelerated colon tumorigenesis in mice.Significance:We identified UshA, a novel T3SS-dependent genotoxin in A/E pathogens that possesses direct DNA digestion activity and confers bacterially accelerated colon tumorigenesis in mice. Our results demonstrate that acute and noninvasive infection with A/E pathogens harbors a far-reaching impact on the development of colon cancer.This article is highlighted in the In This Issue feature, p. 1

Supplementary data contain Supplementary Table 1-3 and Supplementary Figures 1-11.

Disruption remains to be a serious threat to large tokamaks like ITER. The injection speed of disruption mitigation systems (DMS) driven by high pressure gas is limited by the sound speed of the propellent gas. When extrapolating to ITER-like tokamaks, long overall reaction duration and shallow penetration depth due to low injection speed make it stricter for Plasma Control System to predict the impending disruptions. Some disruptions with a short warning time may be unavoidable. Thus, a fast time response and high injection speed DMS is essential for large scale devices. Electromagnetic Pellet-Injection (EMPI) system is a novel massive material injection system aiming to provide rapid and effective disruption mitigation. Based on railgun concept, EMPI can accelerate the payload to over 1000 m/s and shorten the overall reaction time to a few milliseconds. To verify the injection ability and stability of the EMPI, the prototype injector EMPI-1 has been designed and assembled. The preliminary test has been carried out using a 5.9 g armature to propel a dummy pellet and the results suggest that the EMPI configuration has a great potential to be the DMS of the large scale fusion devices.

In the experiments of actively triggering plasma disruption by massive gas injection, the externally applied resonant magnetic perturbation has been used to mitigate the hazard of runaway electron (RE). Motivated by the experiment of multimode coupling to suppress REs on J-TEXT, some typical simulation cases with NIMROD (Non-Ideal MHD with Rotation-Open Discussion) code are carried out to explore the influential mechanism of different relative phases between m/n = 2/1 and m/n = 3/1 magnetic islands on the confinement of REs. Results show that the RE confinement is drastically affected by the relative phase between 2/1 and 3/1 magnetic islands. When the “O point” phase of 2/1 and 3/1 magnetic islands is toroidal 330°, REs can be effectively lost. The fitting curve of the remaining ratio of REs vs. the relative toroidal phase is predicted to approximate a sine-like function dependence. Further studies indicate that the phase difference between coexisting 2/1 and 3/1 islands can affect the radial transport of impurities. The loss of runaway electrons is closely related to the deposition effect of impurity. The impurity is easier to spread into the core region with smaller poloidal phase difference between the radial velocity of impurity and the impurity quantity of Ar.

Backgrounds: Apolipoprotein (apo) B and apo A1 are major protein component of low-density lipoprotein and high-density lipoprotein particles, which are closely linked to lipid metabolism, atherosclerosis, and endothelial function. We sought to investigate whether circulating apoB/A1 ratio could serve as a potential metabolic risk factor for the progression of chronic heart failure (HF). Methods Serum levels of apo B and apo A1 were measured in 1299 consecutive patients with clinical symptoms of chronic HF. Left ventricular ejection fraction (EF) and E/e’ were determined by two-dimensional echocardiography and Doppler flow imaging using standard biplane technique. The relationship of apo B/A1 ratio to classification and etiology of HF was examined. Results Overall, apoB/A1 ratio was gradually decreased from HF with reduced EF (HFrEF), HF with mid-range reduced EF (HFmrEF), to HF with preserved EF (HFpEF), and correlated negatively with left ventricular EF (r=-0.162, p

Background The liver-expressed antimicrobial peptide 2 (LEAP2) is essential in host immunity against harmful pathogens and is only known to act as an extracellular modulator to regulate embryonic development in amphibians. However, there is a dearth of information on the antimicrobial function of amphibian LEAP2. Hence, a LEAP2 homologue from Leptobrachium liui was identified, characterized, and chemically synthesized, and its antibacterial activities and mechanisms were determined. Results In this study, LEAP2 gene (Ll-LEAP2) cDNA was cloned and sequenced from the Chong’an Moustache Toad (Leptobrachium liui). The predicted amino acid sequence of Ll-LEAP2 comprises a signal peptide, a mature peptide, and a prodomain. From sequence analysis, it was revealed that Ll-LEAP2 belongs to the cluster of amphibian LEAP2 and displays high similarity to the Tropical Clawed Frog (Xenopus tropicalis)‘s LEAP2. Our study revealed that LEAP2 protein was found in different tissues, with the highest concentration in the kidney and liver of L. liui; and Ll-LEAP2 mRNA transcripts were expressed in various tissues with the kidney having the highest mRNA expression level. As a result of Aeromonas hydrophila infection, Ll-LEAP2 underwent a noticeable up-regulation in the skin while it was down-regulated in the intestines. The chemically synthesized Ll-LEAP2 mature peptide was selective in its antimicrobial activity against several in vitro bacteria including both gram-positive and negative bacteria. Additionally, Ll-LEAP2 can kill specific bacteria by disrupting bacterial membrane and hydrolyzing bacterial gDNA. Conclusions This study is the first report on the antibacterial activity and mechanism of amphibian LEAP2. With more to uncover, the immunomodulatory functions and wound-healing activities of Ll-LEAP2 holds great potential for future research.

Due to its advantages of high efficiency, high power density at low temperature, fast start-up and zero emission, fuel cells are of great significance in automobile drive application. A car powered by electricity generated by an on-board fuel cell device is called a fuel cell vehicle (FCV). Fuel cells have a large demand for heat dissipation, and the layout space of automotive cooling modules is limited. Based on this situation, a parallel arrangement of multiple radiators is proposed. Using numerical simulation means to verify and optimize the designed multiple circuits cooling system (MCCS), from the original layout scheme based on the Taguchi method to establish the objective function of the reliability design of the MCCS, select A2/B1/C1/D2/E1/F1. In the scheme, the outlet temperature of the fuel cell is finally reduced to 75.8 °C. The cooling performance is improved, and the spatial layout of the individual cooling components can also be optimized. The whole vehicle experiment was carried out under four working conditions of full power idling charging, half power idling charging, constant speed of 40 km/h and constant speed of 80 km/h, to verify the cooling performance of the MCCS and to prove the effectiveness of the MCCS designed in this paper.

Backgrand: Laryngeal squamous cell carcinoma (LSCC), which arises from the laryngeal mucosa, is the main type of laryngeal cancer. An influence of Zinc finger protein 2 (ZIC2) expression on the occurrence and progression of LSCC has not been established. We aim to identify the clinical importance of ZIC2 expression in LSCC and to explore its latent potential mechanisms. Methods:In this study, we studied the relationship between protein and mRNA expression of ZIC2 in LSCC and clinical pathological features and prognoses via mining the high-throughput sequencing data from multiple databases and to use immunohistochemistry (IHC) and integrated analysis. Meanwhile the downstream targets of ZIC2 transcription factor were also predicted with ChlP-seq data. The KEGG, GO and PPI analysis were applied to identified the potential mechanism of ZIC2 in LSCC. After constructing ZIC2 stable expression cells, we attempt to disclose an association between ZIC2 and cell cycle and apoptosis with RT-qPCR and Western blot methods. Cell cycle was detected by flow cytometry. Results: A higher ZIC2 expression in LSCC were found in both protein and mRNA level by integrated analysis (standard mean difference, SMD=1.76 (95% CI, 1.34–2.18)). The IHC staining of ZIC2 protein is nuclear in LSCC. Kinesin family member 14 (KIF14) was explored as the potential downstream target gene of ZIC2. ZIC2 has a binding peak before the transcription start site of KIF14 and their expression were positively correlated with each other. The expression of KIF14 was elevated after overexpressing ZIC2. The KEGG analysis revealed that ZIC2 may involve LSCC by cell cycle. Cell cycle testing revealed that in ZIC2 knockdown cells, G1 phase increased while S phase was decreased. After knockdown ZIC2 expression, the expression of P21 was elevated, Bax protein was increased while Bcl2 decreased. The analysis of the summary receiver operating characteristic (sROC) demonstrated that ZIC2 may have potential to become a diagnostic marker for LSCC. Conclusions: In conclusion, up-regulation of ZIC2 may contribute to LSCC pathogenesis in cell cycle pathway and it may target KIF14 in LSCC, but these need further research in the future.

Here we report the efficient synthesis of a series of 1,3-dioxane derivatives from aromatic alkynes, paraformaldehyde, and a Lewis acid catalyzed reaction at room temperature. This reaction is metal-free and atom-economic. Single crystals of two typical 1,3-dioxane derivatives are obtained. A mechanism that the reaction proceeds through a six- or eight-membered ring intermediate is proposed.

Purpose Automatic guided vehicles (AGVs) are widely used in industrial fields. But most control strategies merely take the lateral force into consideration. This will reduce the accuracy, stability and robustness and will pay additional costs. Therefore, this paper aims to design a control strategy that initially considers lateral force. Thereby, it will improve the accuracy, stability and robustness and reduce the overall cost of AGV. Design/methodology/approach To achieve the goal of comprehensively improving AGV operating performance, this paper presents a new scheme, combining the dual-wheeled chassis model (DCM) using proportional–integral–differential (PID) control and a supporting quick response (QR) code navigation technology. DCM is the core, which analyzes the deviation caused by lateral force. Then, DCM with PID control by the control law is combined to suppress the errors. Meanwhile, QR code navigation technology provides effective data support for the control strategy. Findings Most AGV experiments are carried out in a standard environment. However, this study prepares unfavorable scenarios and operating conditions for the experiments that generate detailed data to demonstrate this study’s strategy, which can make an accurate, stable and robust operation process of AGV under various adverse environmental and mechanical factors. Originality/value This study proposed DCM, fully considering lateral force and converting the force into velocity. Subsequently, PID controls the speed of two wheels to reduce the error. QR code provides an efficient and low – cost way to obtain information. The three are cleverly combined as a novel industrial AGV control strategy, which can comprehensively improve the operating performance while reducing overall costs.

Human gut microbial species found to associate with clinical responses to immune checkpoint inhibitors (ICIs) are often tested in mice using fecal microbiota transfer (FMT), wherein tumor responses in recipient mice may recapitulate human responses to ICI treatment. However, many FMT studies have reported only limited methodological description, details of murine cohorts, and statistical methods. To investigate the reproducibility and robustness of gut microbial species that impact ICI responses, we performed human to germ-free mouse FMT using fecal samples from patients with non-small cell lung cancer who had a pathological response or nonresponse after neoadjuvant ICI treatment. R-FMT mice yielded greater anti-tumor responses in combination with anti-PD-L1 treatment compared to NR-FMT, although the magnitude varied depending on mouse cell line, sex, and individual experiment. Detailed investigation of post-FMT mouse microbiota using 16S rRNA amplicon sequencing, with models to classify and correct for biological variables, revealed a shared presence of the most highly abundant taxa between the human inocula and mice, though low abundance human taxa colonized mice more variably after FMT. Multiple Clostridium species also correlated with tumor outcome in individual anti-PD-L1-treated R-FMT mice. RNAseq analysis revealed differential expression of T and NK cell-related pathways in responding tumors, irrespective of FMT source, with enrichment of these cell types confirmed by immunohistochemistry. This study identifies several human gut microbial species that may play a role in clinical responses to ICIs and suggests attention to biological variables is needed to improve reproducibility and limit variability across experimental murine cohorts.

A novel pyromellitic diimide-extended pillar[6]arene was synthesized in two steps with moderate yield for the first time. It showed a symmetrical stretched hexagon structure and could form 1:2 complexes with polycyclic aromatic hydrocarbons in solution. Interestingly, a linear supramolecular array between complex

Vicinal tertiary and quaternary chiral carbon centers are constructed with high regio-, diastereo- and enantioselectivities via Pd-catalyzed umpolung asymmetric allylic alkylation of hydrazones with monosubstituted allyl reagents by using Kündig type chiral N-heterocyclic carbene as the ligand.

Background The symptoms that patients with major depressive disorder (MDD) experience are the dominant contributing factors to its heavy disease burden. This study sought to identify key symptoms leading to disability in patients with MDD. Methods Subjects consisted of patients who had a 12-month MDD diagnosis based on the China Mental Health Survey (CMHS). World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) was used to assess the degree of disability. The associations between depressive symptoms and disability were analyzed using a linear regression and logistic regression with a complex sampling design. Results Of the 32,552 community residents, 655 patients were diagnosed with 12-month MDD. The disability rate due to MDD was 1.06% (95% CI: 0.85%–1.28%) among adults in Chinese community and 50.7% (95% CI: 44.3%–57.1%) among MDD patients. Depression was associated with all functional losses measured by the WHODAS. Feelings of worthlessness in life or inappropriate guilt, and psychomotor agitation or retardation were the key symptoms related to disability. Economic status, co-morbidity of physical diseases or anxiety disorders were correlates of disability scores. Limitations The disability rate might be underestimated due to the exclusion of MDD patients living in hospitals. The effect of treatments on disability was excluded. Conclusions Psychological symptoms, not somatic symptoms, contribute to disability in MDD patients. Disability worsens when physical diseases or anxiety disorders are present. More attention could be paid to psychological symptoms, physical diseases, and anxiety disorders in MDD patients with disabilities.

As the third-generation supramolecular main structure, calixarenes, especially chiral calixarenes, have been applied to various fields. In this study, the bridging chiral de-tert-butylcalix[4]arene derivatives with an amide group attached to a chiral point was synthesized for the first time, which provided a new group for its structural derivation at the bridging chiral position. The racemic compound 2 was optically resolved by column chromatography on silica gel with the aid of the chiral auxiliary (1S)-(+)-10-camphorsulfonyl chloride, and finally a pair of optically pure bridging chiral de-tert-butylcalix[4]arene derivatives 4a and 4b were obtained. The results of experimental and calculated ECD showed that compounds 4a and 4b were a pair of enantiomers, and their absolute configurations were designated S and R, respectively. This study provides new idea for the derivatization of specific chiral groups based on bridging chiral calix[4]arenes and their chiral resolution.

A new method for the preparation of phenanthrene[2]arene on a large-scale was developed. The synthetic phenanthrene[2]arene has been successfully used as nonporous adaptive crystals for the separation of para-xylene from xylene isomers.

The Yangtze River ecosystem is one of the most important ecosystems in central China. Due to the substantial increase in China’s economy and the improvement of living conditions in rural areas over the past decade, domestic wastewater discharges in rural areas have increased dramatically, seriously affecting the Yangtze River Basin environment, and becoming one of the main obstacles to achieving global sustainable development goals (SDGs). Rural environmental management is very important for the prevention and control of water pollution in the Yangtze River Basin. In order to address the problem of rural domestic sewage treatment, this paper proposes a domestic sewage collection model applicable to rural areas. An operable village sewage treatment plan was developed for Jiangxia District, Wuhan City, specific for each village, based on a previous village sewage treatment plan in Jiangxia District. The plan is cost-effective and ensures a suitable quality of the treated domestic wastewater that meets the local discharge and reuse standards, thus reducing pollution of the Yangtze River and contributing to the restoration of the Yangtze ecological environment.

Intersphincteric resection is the ultimate sphincter-preserving surgical technique for ultralow rectal cancer, but quality-of-life changes after surgery remain unclear. It is also unknown which questionnaire has better associations with functional results for capturing clinical variation in quality-of-life.To assess change in the quality-of-life and its correlation with functional outcomes during post-operative period among patients undergoing intersphincteric resection for ultralow rectal cancer.This was a prospective, observational, single-center study.Colorectal surgery referral center.Patients with ultralow rectal cancer who underwent intersphincteric resection with ileostomy reversal were included.The primary outcome was quality-of-life and functional results at 3-6, 12, and 24 months later after ileostomy closure using validated questionnaires. Secondary outcome was the relationship between quality-of-life and neorectal function.A total of 102 patients (62.7% men) completed follow-up surveys. Wexner incontinence score and Kirwan's incontinence score significantly improved at 12-months following ileostomy reversal, but such improvement in low anterior resection syndrome score was proved until 24-months later (p = 0.01). Condition-specific quality-of-life domains improved over time, with significant changes in lifestyle (p = 0.02) and coping/behavior (p = 0.01), as well as the summary score of Fecal Incontinence Quality of Life (p = 0.02) and visual analog scale score (p0.001). Among health-related quality-of-life domains, the subscale scores did not differ significantly. The functional systems scores were significantly correlated with all the domains of condition-specific quality-of-life, but a few health-related quality-of-life domains. Only weak to moderate associations with the functional outcomes were observed for both quality-of-life questionnaires.Single-center data and limited sample size.Although low anterior resection syndrome persists for years after intersphincteric resection, condition-specific quality-of-life and functional outcomes improve over time. Compared to health-related quality-of-life questionnaires, condition-specific quality-of-life instruments might be preferable to evaluate changes in quality-of-life after surgery. See Video Abstract at http://links.lww.com/DCR/C130.