Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis.

BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease associated with liver-related complications and death. The efficacy and safety of tirzepatide, an agonist of the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, in patients with MASH and moderate or severe fibrosis is unclear. METHODS: We conducted a phase 2, dose-finding, multicenter, double-blind, randomized, placebo-controlled trial involving participants with biopsy-confirmed MASH and stage F2 or F3 (moderate or severe) fibrosis. Participants were randomly assigned to receive once-weekly subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 52 weeks. The primary end point was resolution of MASH without worsening of fibrosis at 52 weeks. A key secondary end point was an improvement (decrease) of at least one fibrosis stage without worsening of MASH. RESULTS: Among 190 participants who had undergone randomization, 157 had liver-biopsy results at week 52 that could be evaluated, with missing values imputed under the assumption that they would follow the pattern of results in the placebo group. The percentage of participants who met the criteria for resolution of MASH without worsening of fibrosis was 10% in the placebo group, 44% in the 5-mg tirzepatide group (difference vs. placebo, 34 percentage points; 95% confidence interval [CI], 17 to 50), 56% in the 10-mg tirzepatide group (difference, 46 percentage points; 95% CI, 29 to 62), and 62% in the 15-mg tirzepatide group (difference, 53 percentage points; 95% CI, 37 to 69) (P<0.001 for all three comparisons). The percentage of participants who had an improvement of at least one fibrosis stage without worsening of MASH was 30% in the placebo group, 55% in the 5-mg tirzepatide group (difference vs. placebo, 25 percentage points; 95% CI, 5 to 46), 51% in the 10-mg tirzepatide group (difference, 22 percentage points; 95% CI, 1 to 42), and 51% in the 15-mg tirzepatide group (difference, 21 percentage points; 95% CI, 1 to 42). The most common adverse events in the tirzepatide groups were gastrointestinal events, and most were mild or moderate in severity. CONCLUSIONS: In this phase 2 trial involving participants with MASH and moderate or severe fibrosis, treatment with tirzepatide for 52 weeks was more effective than placebo with respect to resolution of MASH without worsening of fibrosis. Larger and longer trials are needed to further assess the efficacy and safety of tirzepatide for the treatment of MASH. (Funded by Eli Lilly; SYNERGY-NASH ClinicalTrials.gov number, NCT04166773.).

The outer membrane protein Tp92 of Treponema pallidum delays human neutrophil apoptosis via the ERK, PI3K/Akt, and NF-κB pathways.

Syphilis is a persistent sexually transmitted disease caused by infiltration of the elusive pathogen Treponema pallidum. Despite the prevalence of human polymorphonuclear neutrophils (hPMNs) within cutaneous lesions, which are characteristic of incipient syphilis, their role in T. pallidum infection remains unclear. Tp92 is the only T. pallidum helical outer membrane protein that exhibits structural features similar to those of outer membrane proteins in other gram-negative bacteria. However, the functional mechanism of this protein in immune cells remains unclear. Neutrophils are short-lived cells that undergo innate apoptosis in response to external stimuli that typically influence this process. In this study, we determined that Tp92 impedes the activation of procaspase-3 via the ERK MAPK, PI3K/Akt, and NF-κB signaling pathways, consequently suppressing caspase-3 activity within hPMNs, and thereby preventing hPMNs apoptosis. Furthermore, Tp92 could also modulate hPMNs apoptosis by enhancing the expression of the anti-apoptotic protein Mcl-1, stimulating IL-8 secretion, and preserving the mitochondrial membrane potential. These findings provide valuable insights into the molecular mechanisms underlying T. pallidum infection and suggest potential therapeutic targets for syphilis treatment.

SALL4 in gastrointestinal tract cancers: upstream and downstream regulatory mechanisms.

Effective therapeutic targets and early diagnosis are major challenges in the treatment of gastrointestinal tract (GIT) cancers. SALL4 is a well-known transcription factor that is involved in organogenesis during embryonic development. Previous studies have revealed that SALL4 regulates cell proliferation, survival, and migration and maintains stem cell function in mature cells. Additionally, SALL4 overexpression is associated with tumorigenesis. Despite its characterization as a biomarker in various cancers, the role of SALL4 in GIT cancers and the underlying mechanisms are unclear. We describe the functions of SALL4 in GIT cancers and discuss its upstream/downstream genes and pathways associated with each cancer. We also consider the possibility of targeting these genes or pathways as potential therapeutic options for GIT cancers.

A novel exoskeletal-derived C-type lectin facilitates phagocytosis of hemocytes in the oriental river prawn Macrobrachium nipponense.

C-type lectins (CTLs) execute critical functions in multiple immune responses of crustaceans as a member of pattern recognition receptors (PRRs) family. In this study, a novel CTL was identified from the exoskeleton of the oriental river prawn Macrobrachium nipponense (MnLec3). The full-length cDNA of MnLec3 was 1150 bp with an open reading frame of 723 bp, encoding 240 amino acids. MnLec3 protein contained a signal peptide and one single carbohydrate-recognition domain (CRD). MnLec3 transcripts were widely distributed at the exoskeleton all over the body. Significant up-regulation of MnLec3 in exoskeleton after Aeromonas hydrophila challenged suggested the involvement of MnLec3 as well as the possible function of the exoskeleton in immune response. In vitro tests with recombinant MnLec3 protein (rMnLec3) manifested that it had polysaccharide binding activity, a wide spectrum of bacterial binding activity and agglutination activity only for tested Gram-negative bacteria (Escherichia coli, Vibrio anguillarum and A. hydrophila). Moreover, rMnLec3 significantly promoted phagocytic ability of hemocytes against A. hydrophila in vivo. What's more, MnLec3 interference remarkably impaired the survivability of the prawns when infected with A. hydrophila. Collectively, these results ascertained that MnLec3 derived from exoskeleton took an essential part in immune defense of the prawns against invading bacteria as a PRR.

A Sn-Based Hybrid Ferroelastic Semiconductor with High-Temperature Dielectric Switching.

Organic-inorganic halide hybrids have been extensively developed and used in optoelectronic devices because of their superior performance such as ease of assembly, flexible structural tunability, and excellent optoelectronic properties. Ferroelastic strain might be used to modulate and control photoelectric properties such as photovoltaic voltage, while organic-inorganic hybrid ferroelastic semiconductors remain relatively unexplored. Herein, we successfully design a new Sn-base, lead-free hybrid ferroelastic semiconductor, [TPMA]2[SnCl6] (TPMA = benzyl trimethylammonium). It undergoes a high-temperature -3mF-1-type ferroelastic phase transition at 408 K, and intriguingly, its ferroelastic domains can be simultaneously switched under the stimulation of external heat and stress. The ferroelastic phase transition might be derived from the order-disorder transition of organic cations during heating and cooling. Moreover, [TPMA]2[SnCl6] also demonstrates a high-temperature dielectric switching property around 408 K, which has good stability and reproducibility. With those benefits, [TPMA]2[SnCl6] shows great potential in applications such as energy storage devices, optoelectronic devices, shape memory, intelligent switches, and so on.

Graphene oxide quantum dots-loaded sinomenine hydrochloride nanocomplexes for effective treatment of rheumatoid arthritis via inducing macrophage repolarization and arresting abnormal proliferation of fibroblast-like synoviocytes.

The characteristic features of the rheumatoid arthritis (RA) microenvironment are synovial inflammation and hyperplasia. Therefore, there is a growing interest in developing a suitable therapeutic strategy for RA that targets the synovial macrophages and fibroblast-like synoviocytes (FLSs). In this study, we used graphene oxide quantum dots (GOQDs) for loading anti-arthritic sinomenine hydrochloride (SIN). By combining with hyaluronic acid (HA)-inserted hybrid membrane (RFM), we successfully constructed a new nanodrug system named HA@RFM@GP@SIN NPs for target therapy of inflammatory articular lesions. Mechanistic studies showed that this nanomedicine system was effective against RA by facilitating the transition of M1 to M2 macrophages and inhibiting the abnormal proliferation of FLSs in vitro. In vivo therapeutic potential investigation demonstrated its effects on macrophage polarization and synovial hyperplasia, ultimately preventing cartilage destruction and bone erosion in the preclinical models of adjuvant-induced arthritis and collagen-induced arthritis in rats. Metabolomics indicated that the anti-arthritic effects of HA@RFM@GP@SIN NPs were mainly associated with the regulation of steroid hormone biosynthesis, ovarian steroidogenesis, tryptophan metabolism, and tyrosine metabolism. More notably, transcriptomic analyses revealed that HA@RFM@GP@SIN NPs suppressed the cell cycle pathway while inducing the cell apoptosis pathway. Furthermore, protein validation revealed that HA@RFM@GP@SIN NPs disrupted the excessive growth of RAFLS by interfering with the PI3K/Akt/SGK/FoxO signaling cascade, resulting in a decline in cyclin B1 expression and the arrest of the G2 phase. Additionally, considering the favorable biocompatibility and biosafety, these multifunctional nanoparticles offer a promising therapeutic approach for patients with RA.

Implementation and Evaluation of the FLS Model Nursing in the Rehabilitation of Geriatric Patients with Femoral Neck Fractures.

Objective: To evaluate the effectiveness of FLS model nursing in the rehabilitation of elderly patients after femoral neck fracture surgery. Methods: We retrospectively analyzed data from 89 elderly patients treated surgically for femoral neck fractures, comparing outcomes between those receiving routine nursing (control group, n=44) and FLS model nursing interventions (observation group, n=45). Key metrics included rehabilitation process indicators, hip joint function, self-efficacy, perceived burden, limb stability, and adverse reactions. Results: The observation group showed significantly shorter first out-of-bed time, time for pain disappearance, and length of hospital stay compared to the control group. The observation group also exhibited significantly higher scores in pain, gait, functional activities, and deformity/mobility assessments after the intervention compared to the control group. The GSES score was significantly higher and the SPB score was significantly lower in the observation group after the intervention compared to the control group. The observation group demonstrated significantly higher levels of dynamic balance ability, lower limb muscle strength, and mobile walking ability than the control group. The incidence of adverse reactions was significantly lower in the observation group (8.89%) compared to the control group (36.36%). Conclusion: FLS model nursing intervention has a significant positive effect on the rehabilitation of elderly patients undergoing surgery for femoral neck fractures. Compared to routine nursing intervention, the FLS model nursing intervention can further promote postoperative recovery of hip joint function, improve self-efficacy, alleviate the self-perceived burden, shorten the rehabilitation process, and reduce the risk of adverse postoperative reactions. These findings suggest the FLS model nursing approach holds promise for broader clinical adoption and implementation.

Remarkable Enhancement of Piezoelectric Performance by Heavy Halogen Substitution in Hybrid Perovskite Ferroelectrics.

Piezoelectric materials that enable electromechanical conversion have great application value in actuators, transducers, sensors, and energy harvesters. Large piezoelectric (d33) and piezoelectric voltage (g33) coefficients are highly desired and critical to their practical applications. However, obtaining a material with simultaneously large d33 and g33 has long been a huge challenge. Here, we reported a hybrid perovskite ferroelectric [Me3NCH2Cl]CdBrCl2 to mitigate and roughly address this issue by heavy halogen substitution. The introduction of a large-size halide element softens the metal-halide bonds and reduces the polarization switching barrier, resulting in excellent piezoelectric response with a large d33 (∼440 pC/N), which realizes a significant optimization compared with that of previously reported [Me3NCH2Cl]CdCl3 (You et al. Science2017, 357, 306-309). More strikingly, [Me3NCH2Cl]CdBrCl2 simultaneously shows a giant g33 of 6215 × 10-3 V m/N, far exceeding those of polymers and conventional piezoelectric ceramics. Combined with simple solution preparation, easy processing of thin films, and a high Curie temperature of 373 K, these attributes make [Me3NCH2Cl]CdBrCl2 promising for high-performance piezoelectric sensors in flexible, wearable, and biomechanical devices.

Ferroelectric Phase Transition Driven by Switchable Covalent Bonds.

The mechanism on ferroelectric phase transitions is mainly attributed to the displacive and/or order-disorder transition of internal components since the discovery of the ferroelectricity in 1920, rather than the breaking and recombination of chemical bonds. Here, we demonstrate how to utilize the chemical bond rearrangement in a diarylethene-based crystal to realize the light-driven mm2F1-type ferroelectric phase transition. Such a photoinduced phase transition is entirely driven by switchable covalent bonds with breaking and reformation, enabling the reversible light-controllable ferroelectric polarization switching, dielectric and nonlinear optical bistability. Moreover, light as quantized energy can achieve contactless, nondestructive, and remote-control operations. This work proposes a new mechanism of ferroelectric phase transition, and highlights the significance of photochromic molecules in designing new ferroelectrics for photocontrol data storage and sensing.

Characteristics of phenotypic antibiotic resistance of Helicobacter pylori and its correlation with genotypic antibiotic resistance: A retrospective study in Ningxia.

BACKGROUND: Geographic differences exist in the antibiotic resistance patterns of Helicobacter pylori. Personalized treatment regimens based on local or individual resistance data are essential. We evaluated the current status of H. pylori resistance in Ningxia, analyzed resistance-related factors, and assessed the concordance of phenotypic and genotypic resistance. METHODS: Strains were isolated from the gastric mucosa of patients infected with H. pylori in Ningxia and relevant clinical information was collected. Phenotypic antibiotic susceptibility assays (Kirby-Bauer disk diffusion) and antibiotic resistance gene detection (Sanger sequencing) were performed. RESULTS: We isolated 1955 H. pylori strains. The resistance rates of H. pylori to amoxicillin, levofloxacin, clarithromycin, and metronidazole were 0.9%, 42.4%, 40.4%, and 94.2%, respectively. Only five tetracycline-resistant and one furazolidone-resistant strain were identified. Overall, 3.3% of the strains were sensitive to all six antibiotics. Multidrug-resistant strains accounted for 22.9%, of which less than 20% were from Wuzhong. Strains isolated from women and patients with nonulcerative disease had higher rates of resistance to levofloxacin and clarithromycin. Higher rates of resistance to metronidazole, levofloxacin, and clarithromycin were observed in the older age group than in the younger age group. The kappa coefficients of phenotypic resistance and genotypic resistance for levofloxacin and clarithromycin were 0.830 and 0.809, respectively, whereas the remaining antibiotics showed poor agreement. CONCLUSION: H. pylori antibiotic resistance is severe in Ningxia. Therefore, furazolidone, amoxicillin, and tetracycline are better choices for the empirical therapy of H. pylori infection in this region. Host sex, age, and the presence of ulcerative diseases may affect antibiotic resistance of the bacteria. Personalized therapy based on genetic testing for levofloxacin and clarithromycin resistance may be a future direction for the eradication therapy of H. pylori infection in Ningxia.

H/F Substitution Achieved Enantiomeric Organic Inorganic Hybrid Perovskites and Trigonal Structure [DMFP]3(CdBr3)(CdBr4).

Organic-inorganic hybrid perovskites (OIHPs) have been emerging as a hot research topic due to their potential applications in energy storage, semiconductors, and electronic devices. Herein, we systematically investigated the synthesis and phase transition behaviors of the enantiomeric OIHPs, (R) and (S)-N,N-dimethyl-3-fluoropyrrolidinium cadmium bromide ([DMFP][CdBr3]), and the hybrid trigonal structure [DMFP]3 (CdBr3)(CdBr4). The enantiomers have a mirror-symmetric structure and enhanced solid-state phase transition points of 417 and 443 K, in contrast to the nonfluorinated parent compound, N,N-dimethyl-pyrrolidinium cadmium bromide ([DMP][CdBr3], 385 K). Moreover, racemic H/F substitution on the pyrrolidinium cations leads to the formation of a trigonal compound, showing above-room-temperature structural phase transition and dominant ferroelasticity. This work discovers chiral enantiomeric OIHPs through H/F substitution, demonstrating a useful chemical synthesis strategy for exploring novel phase transition materials.

The additional nitrogen atom breaks the uranyl structure: a combined photoelectron spectroscopy and theoretical study of NUO2.

We report a joint photoelectron spectroscopic and relativistic quantum chemistry study on gaseous NUO2-. The electron affinity (EA) of the neutral NUO2 molecule is reported for the first time with a value of 2.602(28) eV. The U-O and U-N stretching vibrational modes for the ground state and the first excited state are observed for NUO2. The geometric and electronic structures of both the anions and the corresponding neutrals are investigated by relativistic quantum chemistry calculations to interpret the photoelectron spectra and to provide insights into the nature of the chemical bonding. Both the ground state of the anion and neutral are calculated to be planar structures with C2v symmetry. Unlike the "T"-shape structure of UO3 which has a quasi-linear O-U-O angle, both the ground-state geometries of the anion and neutral have O-U-O bond angles of around 90°. The significant contraction of the O-U-O bond angle indicates the strong interaction between the U and N atoms compared with the "additional" oxygen in UO3. The chemical bonding calculation indicates that multiple bonding of U(VI) can occur in NUO2- and NUO2, and the UVI-N bond is significantly more covalent than the U-O bond. The current experimental and theoretical results reveal the difference between the U-N and U-O bond in the unified molecular system, and expand our understanding of the bonding capacities of actinide elements with the nitrogen atom.

Enhancing resilient coping strategies for quality of life in Chinese adult children caregiving for parents with advanced cancer: a cross-sectional study.

PURPOSE: This study investigated the mediating role of individual resilience in the relationship between caregiver burden and quality of life (QoL) among Chinese adult children providing care to their parents with advanced cancer, with the aim to inform effective coping strategies and positive caregiving outcomes. METHODS: In a cross-sectional design, 614 caregivers from multiple centers, whose parents were undergoing chemotherapy and/or radiotherapy, completed questionnaires encompassing demographics, caregiver burden, symptoms of anxiety and depression, resilience, and QoL. RESULTS: Findings revealed a moderate level of caregiver burden among participants, significantly influenced by factors including education level, family income, single-child status, and participation in social media patient support groups. Caregivers who were only children or involved in patient support groups reported higher burden. Importantly, path analysis showed a significant impact of caregiver burden, anxiety, and depression on QoL, with these relationships being mediated by individual resilience. CONCLUSIONS: Chinese adult child caregivers face a considerable burden, negatively influencing their QoL. Individual resilience, a modifiable factor, was identified as a critical mediator in this relationship, mitigating the negative implications of caregiver burden, anxiety, and depression. These findings underscore the need for caregiver interventions that consider not only demographics but also the socio-psychological dynamics of caregiving to enhance caregiver QoL.

Combined endoscope and low-temperature plasma knife for bilateral nasal vestibular cyst with sinus tract formation.

BACKGROUND: Nasal vestibular cyst is a non-dental cystic mass that occurs under the skin at the base of the nasal vestibule. The primary treatment is a transnasal endoscopic excision of the cyst wall at the base of the nose to open the cyst wall at the base of the nasal cavity, namely, marsupialization. METHODS: We present a patient with bilateral nasal vestibular cysts with sinus tract formation. This patient underwent marsupialization under general anesthesia because of the presence of facial swelling and other symptoms. RESULTS: After a 4-year follow-up, our studied case show a significantly improved radiological outcome and clinical prognosis. CONCLUSIONS: Compared to unilateral lesions, bilateral nasal vestibular cysts are more likely to be underdiagnosed due to the deceptive nature of the bilateral anatomy observed from the radiological findings. With this rare clinical case reported in this study, we hope our experience in diagnosis and treatment will provide a reference for otolaryngologist surgeons managing similar patients.

Spirituality and Attitudes Toward Death Among Older Adults in Rural and Urban China: A Cross-Sectional Study.

The purpose of this study was to investigate spirituality and attitudes toward death among rural and urban elderly. We asked 134 older adults from rural areas and 128 from urban areas to complete a self-administrated questionnaire including the Spiritual Self-assessment Scale and Death Attitude Scale. The fear and anxiety of death, escape acceptance, natural acceptance, approach acceptance, and death avoidance scores of older adults living in rural areas were higher than those living in urban areas. The construction of social infrastructure and medical care should be strengthened in rural areas so as to improve older adults' attitudes toward death.

[Multi-component content determination of Dracocephalum tanguticum by quantitative analysis of multi-components by single-marker].

This study aims to establish a method for the simultaneous determination of 7 active components in Dracocephalum tanguticum and to evaluate the quality of medicinal materials from different habitats. The method was established with high performance liquid chromatography(HPLC) and the gradient elution was performed with the mobile phase of acetonitrile-methanol-0.2% phosphoric acid solution at a column temperature of 35 ℃, an injection volume of 15 µL, and a flow rate of 0.6 mL·min~(-1). The detection wavelength was set as 215 nm. With rosmarinic acid as the internal reference, the relative correction factors and the content of other 6 components were calculated. The results were compared with those obtained with the external standard method. The results showed that the samples from Huangzhong county, Qinghai province had the best quality, with the highest content of p-hydroxybenzoic acid, cosmosiin, rosmarinic acid, oleanolic acid, and ursolic acid(9.29, 12.14, 6.02, 3.11, 17.67 mg·g~(-1) respectively). The samples from Chaya county, Tibet autonomous region ranked the second, with the highest content of betulin and betulinic acid(15.53, 7.17 mg·g~(-1), respectively). The method is accurate, reliable, and repeatable and suitable for the simultaneous determination of multiple components in D. tanguticum. The content of functional components varied in the samples from different producing areas and can be used as the indicator for the quality evaluation of medicinal materials.

In vitro promotion of SDF-1α on the migration and proliferation of C-kit+ cardiac stem cells in neonatal mice.

The aim of this study was to explore the In Vitro effects of stromal-derived factor-1α (SDF-1α) on the migration and proliferation of c-kit+ cardiac stem cells. The lentivirus containing SDF-1α (LV-SDF-1α) was constructed. Primary myocardial fibroblasts were transfected by LV-SDF-1α, followed by primary culture of cardiac tissue cells and separation of c-kit+ cardiac stem cells with a flow cytometer, in order to investigate the effects of SDF-1α on the migration and proliferation of c-kit+ cardiac stem cells using cell co-culture, immunofluorescence and EdU tracing technologies. The results showed that myocardial fibroblasts could secrete SDF-1α after the transfection with LV-SDF-1α. High-purity c-kit+ cardiac stem cells were obtained through flow cytometry sorting and the positive rate was about 40%. The c-kit+ cardiac stem cells cultured In Vitro could be differentiated into cTnT positive cardiomyocyte-like cells. After co-culture of myocardial fibroblasts and c-kit+ cardiac stem cells transfected with lentivirus, SDF-1α might increase the migration of c-kit+ cardiac stem cells, but SDF-1α did not promote the proliferation of c-kit+ cardiac stem cells. In conclusion, the myocardial fibroblasts transfected with lentivirus can highly express SDF-1α, c-kit+ cardiac stem cells can be differentiated into cTnT positive cardiomyocyte-like cells and SDF-1α can effectively enhance the migration of c-kit+ cardiac stem cells but fails to stimulate the proliferation.

Contactless Manipulation of Write-Read-Erase Data Storage in Diarylethene Ferroelectric Crystals.

The optical manipulation of polarization has gained widespread attention because it offers a promising route to new contactless memories and switches. However, the current research basically focuses on the photocontrol of data storage rather than data reading, which cannot realize the whole process of contactless write-read-erase data storage. Here, we present a pair of enantiomorphic diarylethene derivative ferroelectric crystals, showing a light-driven phase transition triggered by photoisomerization between the open and closed forms. Under the visible light, they exhibit a binary-domain state in the open form with white color and the band gap of 3.26 eV, while they show a single-domain state in the closed form with blue color and the band gap of 1.68 eV after UV irradiation of 254/365 nm. In addition to writing and erasing ferroelectric domains with light, we can also use light to read their color to determine the polarization state of domains. Moreover, diarylethene derivatives have better thermal stability, higher photoexcited conversion efficiency, and larger changes of the absorption wavelength between two isomers than those in salicylideneaniline derivatives. This work not only discovers the first diarylethene-based ferroelectric crystals but also successfully realizes completely contactless manipulation of write-read-erase data storage in the organic ferroelectric semiconductors.

Axial-Chiral BINOL Multiferroic Crystals with Coexistence of Ferroelectricity and Ferroelasticity.

Chirality exists everywhere from natural amino acids to particle physics. The introduction of point chirality has recently been shown to be an efficient strategy for the construction of molecular ferroelectrics. In contrast to point chirality, however, axial chirality is rarely used to design ferroelectrics so far. Here, based on optically active 1,1'-bi-2-naphthol (BINOL), which has been applied extensively as a versatile chiral reagent in asymmetric catalysis, chiral recognition, and optics, we successfully design a pair of axial-chiral BINOL multiferroics, (R)-BINOL-DIPASi and (S)-BINOL-DIPASi. They experience a 2F1-type full ferroelectric/ferroelastic phase transition at a high temperature of 362 and 363 K, respectively. Piezoelectric force microscopy and polarization-voltage hysteresis loops demonstrate their ferroelectric domains and domain switching, and polarized light microscopy visualizes the evolution of stripe-shaped ferroelastic domains. The axial-chiral BINOL building block promotes the generation of the polar structure and ferroelectricity, and the organosilicon component increases the rotational energy barrier and thus the phase transition temperature. This work presents the first axial-chiral high-temperature multiferroic crystals, offering an efficient path for designing molecular multiferroics through the introduction of axial chirality.

A Survey of Helicobacter pylori Antibiotic-Resistant Genotypes and Strain Lineages by Whole-Genome Sequencing in China.

Antibiotic resistance is the most important factor leading to failed Helicobacter pylori eradication therapy, and personalized treatment based on antibiotic susceptibility is becoming increasingly important. To strengthen the understanding of antibiotic genotypic resistance of H. pylori and identify new antibiotic resistance loci, in this study, we identified phenotypic resistance information for 60 clinical isolates and compared the concordance of phenotypic and genotypic resistance using whole-genome sequencing (WGS). Clarithromycin and levofloxacin genotypic resistance was in almost perfect concordance with phenotypic resistance, with kappa coefficients of 0.867 and 0.833, respectively. All strains with the R16H/C mutation and truncation in rdxA were metronidazole resistant, with 100% specificity. For other genes of concern, at least one phenotypically sensitive strain had a previous mutation related to antibiotic resistance. Moreover, we found that the A1378G mutation of HP0399 and the A149G mutation of FabH might contribute to tetracycline resistance and multidrug resistance, respectively. Overall, the inference of resistance to clarithromycin and levofloxacin from genotypic resistance is reliable, and WGS has been very helpful in discovering novel H. pylori resistance loci. In addition, WGS has also enhanced our study of strain lineages, providing new ways to understand resistance information and mechanisms.