Causal associations between the gut microbiota and multiple myeloma: a two-sample Mendelian randomization study.

Background: Previous observational studies have indicated a potential association between the gut microbiota and multiple myeloma (MM). However, the relationship between the gut microbiota and MM remains unclear. This study aimed to ascertain the existence of a causal link between the gut microbiota and MM. Methods: To investigate the potential causal relationship between gut microbiota and MM, a two-sample Mendelian randomization (MR) analysis was conducted. Exposure data was obtained from the MiBioGen consortium, which provided genetic variants associated with 211 bacterial traits. MM outcome data was obtained from the FinnGen consortium. The selection of Single nucleotide polymorphisms estimates was performed through meta-analysis using inverse-variance weighting, and sensitivity analyses were conducted using weighted median, MR Egger, Simple mode, and MR-PRESSO. Results: The results of the study demonstrated a significant positive correlation between the genus Eubacterium ruminantium group and the risk of MM (OR 1.71, 95% CI 1.21 to 2.39). Conversely, the genus: Dorea (OR 0.46, 95% CI 0.24 to 0.86), Coprococcus1 (OR 0.47, 95% CI 0.22 to 1.00), RuminococcaceaeUCG014 (OR 0.57, 95% CI 0.33 to 0.99), Eubacterium rectale group (OR 0.37, 95% CI 0.18 to 0.77), and order: Victivallales (OR 0.62, 95% CI 0.41-0.94), class: Lentisphaeria (OR 0.62, 95% CI 0.41 to 0.94), exhibited a negative association with MM. The inverse variance weighting analysis provided additional support for these findings. Conclusion: This study represents an inaugural exploration of MR to investigate the connections between gut microbiota and MM, thereby suggesting potential significance for the prevention and treatment of MM.

Preconception depression reduces fertility: a couple-based prospective preconception cohort.

STUDY QUESTION: Is preconception depression associated with time to pregnancy (TTP) and infertility? SUMMARY ANSWER: Couples with preconception depression needed a longer time to become pregnant and exhibited an increased risk of infertility. WHAT IS KNOWN ALREADY: Preconception depression in women contributes to impaired fertility in clinical populations. However, evidence from the general population-especially based on couples-is relatively scant. STUDY DESIGN SIZE DURATION: A couple-based prospective preconception cohort study was performed in 16 premarital examination centers between April 2019 and June 2021. The final analysis included 16 521 couples who tried to conceive for ≤6 months at enrollment. Patients with infertility were defined as those with a TTP ≥12 months and those who conceived through ART. PARTICIPANTS/MATERIALS SETTING METHODS: Couples' depression was assessed using the Patient Health Questionnaire-9 at baseline. Reproductive outcomes were obtained via telephone at 6 and 12 months after enrollment. Fertility odds ratios (FORs) and infertility risk ratios (RRs) in different preconception depression groups were analyzed using the Cox proportional-hazard models and logistic regression, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 16 521 couples analyzed, 10 834 (65.6%) and 746 (4.5%) couples achieved pregnancy within the first 6 months and between the 6th and 12th months, respectively. The median (P25, P75) TTP was 3.0 (2.0, 6.0) months. The infertility rate was 13.01%. After adjusting for potential confounders, in the individual-specific analyses, we found that preconception depression in women was significantly related to reduced odds of fertility (FOR = 0.947, 95% CI: 0.908-0.988), and preconception depression in either men or women was associated with an increased risk of infertility (women: RR = 1.212, 95% CI: 1.076-1.366; men: RR = 1.214, 95% CI: 1.068-1.381); in the couple-based analyses, we found that-compared to couples where neither partner had depression-the couples where both partners had depression exhibited reduced fertility (adjusted FOR = 0.904, 95% CI: 0.838-0.975). The risk of infertility in the group where only the woman had depression and both partners had depression increased by 17.8% (RR = 1.178, 95% CI: 1.026-1.353) and 46.9% (RR = 1.469, 95% CI: 1.203-1.793), respectively. LIMITATIONS REASONS FOR CAUTION: Reporting and recall bias were unavoidable in this large epidemiological study. Some residual confounding factors-such as the use of anti-depressants and other medications, sexual habits, and prior depressive and anxiety symptoms-remain unaddressed. We used a cut-off score of 5 to define depression, which is lower than prior studies. Finally, we assessed depression only at baseline, therefore we could not detect effects of temporal changes in depression on fertility. WIDER IMPLICATIONS OF THE FINDINGS: This couple-based study indicated that preconception depression in individuals and couples negatively impacts couples' fertility. Early detection and intervention of depression to improve fertility should focus on both sexes. STUDY FUNDING/COMPETING INTERESTS: This work was supported by grants from the National Natural Science Foundation of China (No. 82273638) and the National Key Research and Development Program of China (No. 2018YFC1004201). All authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Laryngeal paraganglioma: The analysis of misdiagnosed cases and literature review.

Laryngeal paraganglioma (LP) is an exceptionally rare neuroendocrine tumor, underscoring importance of accurate identification to preclude misdiagnoses. In this review, we presented two typical misdiagnosed LPs, and offered reviews of LP cases reported over the preceding decade and all documented misdiagnosed LP cases. Furthermore, we systematically investigated the underlying causes of misdiagnosis and elucidated key points for effective differentiation. A retrospective analysis of 28 LP cases revealed a predominant occurrence in middle-aged women, with an average history of 25.1 months. Through an analysis of all misdiagnosed cases (n = 37), supraglottic LPs were frequently misidentified as laryngeal carcinomas and vascular tumors, while subglottic LPs were often misdiagnosed as thyroid cancers. And the occurrence of misdiagnosis resulted in delayed and inappropriate treatments, contributing to the deterioration of LP patients (14 cases, 37.8%). In conclusion, this review endeavored to heighten awareness of LPs, with the ultimate goal of advancing diagnostic precision and enhancing patient outcomes.

Extracellular Vesicles from Urine-Derived Stem Cell for Tissue Engineering and Regenerative Medicine.

The potential of urine-derived stem cells (USCs) for tissue engineering and regenerative medicine has attracted much attention during the last few decades. However, it has been suggested that the effects of the USCs may be endowed by their paracrine extracellular vesicles (EVs) rather than their differentiation. Compared with the USCs, the USC-EVs can cross the barriers more easily and safely, and their inclusions may mediate intercellular communication and promote the tissue repair. This article has summarized the current knowledge and applications about the USC-EVs in tissue engineering and regenerative medicine, and discussed the prospects and challenges for using them as an alternative to cell therapy. Impact statement Urine-derived stem cells (USCs) represent a newly discovered type of stem cells, and studies have proved that the beneficial effects of the USCs may be manifested through their paracrine extracellular vesicles (EVs) rather than through their own differentiation, which opens up new avenues for tissue engineering and regenerative medicine strategies. Therefore, this review aims to summarize the latest research progress and potential clinical applications of the USC-EVs, highlighting the promising potential of the USC-EVs as a therapeutic option in kidney regeneration, genital regeneration, nerve regeneration, bone and cartilage regeneration, and wound healing.

Chitosan/polyacrylic acid/octadecene double-crosslinked network hydrogel functionalized porous silica microspheres for multimode liquid chromatographic separation.

In this study, chitosan (CS) and polyacrylic acid (PAA) were used to construct a double-crosslinked network hydrogel, which was employed as the functional material for silica microspheres to prepare a CS/PAA hydrogel modified liquid chromatographic stationary phase. During preparation, octadecene (ODE) was introduced into the CS/PAA hydrogel to improve its hydrophobicity and separation ability. The electrostatic interaction between the amino group of CS and the carboxyl group of PAA effectively prevented the swelling of the CS/PAA hydrogel, which ensured the successful application of the obtained CS/PAA hydrogel@SiO2 in chromatographic analysis. Polar nucleosides/bases and B-vitamins were selectively separated using hydrophilic interaction liquid chromatography. Hydrophobic polycyclic aromatic hydrocarbons and alkylphenols were effectively separated through reversed-phase liquid chromatography. Moreover, the effective separation of aromatic positional isomers and chiral enantiomers was achieved. This study confirms the potential application of the CS/PAA hydrogel in chromatographic separation. What is noteworthy is that the method developed in this study also provides a feasible strategy to solve the swelling issue associated with the hydrogel-based liquid chromatographic stationary phase.

[Research status and prospect of tissue engineering technology in treatment of atrophic rhinitis].

Objective: To review the research progress of the feasibility of a new treatment method for atrophic rhinitis (ATR) based on tissue engineering technology (seed cells, scaffold materials, and growth factors), and provide new ideas for the treatment of ATR. Methods: The literature related to ATR was extensively reviewed. Focusing on the three aspects of seed cells, scaffold materials, and growth factors, the recent research progress of ATR treatment was reviewed, and the future directions of tissue engineering technology to treat ATR were proposed. Results: The pathogenesis and etiology of ATR are still unclear, and the effectiveness of the current treatments are still unsatisfactory. The construction of a cell-scaffold complex with sustained and controlled release of exogenous cytokines is expected to reverse the pathological changes of ATR, promoting the regeneration of normal nasal mucosa and reconstructing the atrophic turbinate. In recent years, the research progress of exosomes, three-dimensional printing, and organoids will promote the development of tissue engineering technology for ATR. Conclusion: Tissue engineering technology can provide a new treatment method for ATR.

Requirements in structure for chiral recognition of chitosan derivatives.

In order to investigate the influence of a minor variation in structure of N-acyl chitosan derivatives on enantioseparation, chiral selectors (CSs) of chitosan 3,6-bis(phenylcarbamate)-2-(phenylacetamide)s and chitosan 3,6-bis(phenylcarbamate)-2-(cyclohexylacetamide)s were synthesized. The corresponding chiral stationary phases (N-PhAc CSPs and N-cHeAc CSPs) were also prepared, respectively, with the two series of CSs. Enantioseparation results revealed that the N-PhAc CSPs were better than the N-cHeAc ones in enantioseparation. Thus, benzyl group (Bn) at C2 should be more preferable to enantioseparation than cyclohexylmethyl (cyclohexyl-CH2-) at the same position. Because N-PhAc CSPs exhibited higher enantioseparation capability than chitosan 3,6-bis(phenylcarbamate)-2-(benzamide) based CSPs (N-Bz CSPs), the Bn should also be more beneficial to enantioseparation than phenyl group (Ph) at C2 in N-Bz CSPs. In addition, it was found that, the cyclohexyl group at C2 in chitosan 3,6-bis(phenylcarbamate)-2-(cyclohexylformamide) CSPs was better than cyclohexyl-CH2- in N-cHeAc CSPs to enantioseparation. In a word, a minor variation at C2 of chitosan derivatives significantly affected enantioseparation. After the prepared CSPs were stood for six months, their enantioseparation capabilities were changed obviously, and the changes were probably related to nature, position and number of a substituent on Ph connected to carbamates at C3 and C6 of the CSs.

Maple Leaf Inspired Conductive Fiber with Hierarchical Wrinkles for Highly Stretchable and Integratable Electronics.

Stretchable and durable conductors are significant to the development of wearable devices, robots, human-machine interfaces, and other artificial intelligence products. However, the desirable strain-insensitive conductivity and low hysteresis are restricted by the failure of stretchable structures and mismatch of mechanical properties (rigid conductive layer and elastic core substrate) under large deformation. Here, based on the principles of fractal geometry, a stretchable conductive fiber with hierarchical wrinkles inspired by the unique shape of the maple leaf was fabricated by combining surface modification, interfacial polymerization, and improved prestrain finishing methods to break through this dilemma. The shape and size of wrinkles predicted by buckling analysis via the finite element method fit well with that of actual wrinkles (30-80 µm of macro wrinkles and 4-6 µm of micro wrinkles) on the fabricated fiber. Such hierarchically wrinkled conductive fiber (HWCF) exhibited not only excellent strain-insensitive conductivity denoted by the relative resistance change ΔR/R0 = 0.66 with R0 the original resistance and ΔR the change of resistance after the concrete strain reaching up to 600%, but also low hysteresis (0.04) calculated by the difference in area between stretching and releasing curve of the ΔR/R0 strain under 300% strain and long-term durability (>1000 stretching-releasing cycles). Furthermore, the elastic conductive fiber with such a bionic structure design can be applied as highly stretchable electrical circuits for illumination and monitors for the human motion under large strains through tiny and rapid resistance changes as well. Such a smart biomimetic material holds great prospects in the field of stretchable electronics.

Chromosome 1q21 gain is an adverse prognostic factor for newly diagnosed multiple myeloma patients treated with bortezomib-based regimens.

Chromosome 1q21 aberration is one of the most common cytogenetic abnormalities in multiple myeloma, and is considered an important prognostic factor. The present study analyzed the clinical relevance and prognostic impact of 1q21 gain in 194 patients with newly diagnosed multiple myeloma treated with bortezomib-based regimens. 1q21 gain was detected in 45.9% (89/194) of patients, and those with 1q21 gain had a worse prognosis. Strikingly, our results showed that excluding the effects of other coinciding genetic anomalies, patients carrying at least four copies of 1q21 had worse survival outcome. Moreover, del(13q) strongly correlates with 1q21 gain, and the coexistence of del(13q) and 1q21 gain plays an important role in reducing PFS and OS times. Therefore, 1q21 gain should be considered a high-risk feature in multiple myeloma patients treated with a bortezomib-based regimen.

Development and Validation of a Novel Prognostic Model for Overall Survival in Newly Diagnosed Multiple Myeloma Integrating Tumor Burden and Comorbidities.

Background: Multiple myeloma (MM) is a highly heterogeneous disease with enormously variable outcomes. It remains to be a major challenge to conduct a more precise estimation of the survival of MM patients. The existing stratifications attached less importance to the prognostic significance of comorbidities. In the present study, we aimed to develop and validate a novel and simple prognostic stratification integrating tumor burden and comorbidities measured by HCT-CI. Method: We retrospectively enrolled 385 consecutive newly diagnosed multiple myeloma (NDMM) patients in Xijing Hospital from January 2013 to December 2020. The cohort between January 2016 and December 2020 was selected as development cohort (N = 233), and the cohort between January 2013 and December 2015 was determined as validation cohort (N = 152). By using LASSO analysis and univariate and multivariable Cox regression analyses, we developed the MM-BHAP model in the way of nomogram composed of ß2-MG, HCT-CI, ALB, and PBPC. We internally and externally validated the MM-BHAP model and compared it with ISS stage and R-ISS stage. Results: The MM-BHAP model was superior to the ISS stage and partially better than the R-ISS stage according to time-dependent AUC, time-dependent C-index, DCA, IDI, and continuous NRI analyses. In predicting OS, only the MM-BHAP stratification clearly divided patients into three groups while both the ISS stage and R-ISS stage had poor classifications in patients with stage I and stage II. Moreover, the MM-BHAP stratification and the R-ISS stage performed well in predicting PFS, but not for the ISS stage. Besides, the MM-BHAP model was also applied to the patients with age ≤65 or age >65 and with or without HRCA and could enhance R-ISS or ISS classifications. Conclusions: Our study offered a novel simple MM-BHAP stratification containing tumor burden and comorbidities to predict outcomes in the real-world unselected NDMM population.

Conductive biomaterials for cardiac repair: A review.

Myocardial infarction (MI) is one of the fatal diseases in humans. Its incidence is constantly increasing annually all over the world. The problem is accompanied by the limited regenerative capacity of cardiomyocytes, yielding fibrous scar tissue formation. The propagation of electrical impulses in such tissue is severely hampered, negatively influencing the normal heart pumping function. Thus, reconstruction of the internal cardiac electrical connection is currently a major concern of myocardial repair. Conductive biomaterials with or without cell loading were extensively investigated to address this problem. This article introduces a detailed overview of the recent progress in conductive biomaterials and fabrication methods of conductive scaffolds for cardiac repair. After that, the advances in myocardial tissue construction in vitro by the restoration of intercellular communication and simulation of the dynamic electrophysiological environment are systematically reviewed. Furthermore, the latest trend in the study of cardiac repair in vivo using various conductive patches is summarized. Finally, we discuss the achievements and shortcomings of the existing conductive biomaterials and the properties of an ideal conductive patch for myocardial repair. We hope this review will help readers understand the importance and usefulness of conductive biomaterials in cardiac repair and inspire researchers to design and develop new conductive patches to meet the clinical requirements. STATEMENT OF SIGNIFICANCE: After myocardial infarction, the infarcted myocardial area is gradually replaced by heterogeneous fibrous tissue with inferior conduction properties, resulting in arrhythmia and heart remodeling. Conductive biomaterials have been extensively adopted to solve the problem. Summarizing the relevant literature, this review presents an overview of the types and fabrication methods of conductive biomaterials, and focally discusses the recent advances in myocardial tissue construction in vitro and myocardial repair in vivo, which is rarely covered in previous reviews. As well, the deficiencies of the existing conductive patches and their construction strategies for myocardial repair are discussed as well as the improving directions. Confidently, the readers of this review would appreciate advantages and current limitations of conductive biomaterials/patches in cardiac repair.

Chiral separation materials based on derivatives of 6-amino-6-deoxyamylose.

In order to develop new type of chiral separation materials, in this study, 6-amino-6-deoxyamylose was used as chiral starting material with which 10 derivatives were synthesized. The amino group in 6-amino-6-deoxyamylose was selectively acylated and then the hydroxyl groups were carbamoylated yielding amylose 6-amido-6-deoxy-2,3-bis(phenylcarbamate)s, which were employed as chiral selectors (CSs) for chiral stationary phases of high-performance liquid chromatography. The resulted 6-amido-6-deoxyamyloses and amylose 6-amido-6-deoxy-2,3-bis(phenylcarbamate)s were characterized by IR, 1 H NMR, and elemental analysis. Enantioseparation evaluations indicated that most of the CSs demonstrated a moderate chiral recognition capability. The 6-nonphenyl (6-nonPh) CS of amylose 6-cyclohexylformamido-6-deoxy-2,3-bis(3,5-dimethylphenylcarbamate) showed the highest enantioselectivity towards the tested chiral analytes; the phenyl-heterogeneous (Ph-hetero) CS of amylose 6-(4-methylbenzamido)-6-deoxy-2,3-bis(3,5-dimethylphenylcarbamate) baseline separated the most chiral analytes; the phenyl-homogeneous (Ph-homo) CS of amylose 6-(3,5-dimethylbenzamido)-6-deoxy-2,3-bis(3,5-dimethylphenylcarbamate) also exhibited a good enantioseparation capability among the developed CSs. Regarding Ph-hetero CSs, the enantioselectivity depended on the combination of the substituent at 6-position and that at 2- and 3-positions; as for Ph-homo CSs, the enantioselectivity was related to the substituent at 2-, 3-, and 6-positions; with respect to 6-nonPh CSs, the retention factor of most analytes on the corresponding CSPs was lower than that on Ph-hetero and Ph-homo CSPs in the same mobile phases, indicating π-π interactions did occur during enantioseparation. Although the substituent at 6-position could not provide π-π interactions, the 6-nonPh CSs demonstrated an equivalent or even higher enantioselectivity compared with the Ph-homo and Ph-hetero CSs.

Endothelial HNF4α potentiates angiogenic dysfunction via enhancement of vascular endothelial growth factor resistance in T2DM.

Although both hyperprocoagulant status, characterized by elevated thrombin levels, and vascular endothelial growth factor (VEGF) resistance, marked by attenuated expression of VEGFR2 (also called FLK1 or KDR), are known to contribute importantly to an increased risk of vascular events in diabetes mellitus type 2 (T2DM), it remains obscure whether these two biological events regulate angiogenic response in a coordinated manner. We show here that endothelial expression of hepatocyte nuclear factor 4α (HNF4α) was significantly upregulated in rodents and humans with T2DM, and HNF4α upregulation by thrombin was dependent on activation of multiple pathways, including protein kinase B, c-Jun N-terminal kinase, p38, oxidative stress, protein kinase C, and AMPK (5'-adenosine monophosphate (AMP)-activated protein kinase). Functionally, HNF4α inhibited VEGF-mediated endothelial proliferation and migration, and blunted VEGF-stimulated in vitro angiogenesis, thus rendering endothelial cells unresponsive to established angiogenic VEGF stimulation. Mechanistically, HNF4α potentiated the endothelial VEGF resistance through the direct transcriptional repression of FLK1 gene. From a therapeutic standpoint, overexpression of the exogenous FLK1 successfully rescued HNF4α-inhibited angiogenic response to VEGF and potentiated VEGF-stimulated in vitro tube formation. Considering a strong association between HNF4A deregulation and increased risk of T2DM, our findings suggest that HNF4α may act as a critical converging point linking hyperprocoagulant condition to VEGF resistance in diabetic ECs, and repression of FLK1 expression by thrombin-induced HNF4α mediates, at least partially, the vascular dysfunction caused by T2DM.