Substituent Impact on Quinoxaline Performance and Degradation in Redox Flow Batteries.

Aqueous redox flow batteries (RFBs) are attractive candidates for low-cost, grid-scale storage of energy from renewable sources. Quinoxaline derivatives represent a promising but underexplored class of charge-storing materials on account of poor chemical stability in prior studies (with capacity fade rates >20%/day). Here, we establish that 2,3-dimethylquinoxaline-6-carboxylic acid (DMeQUIC) is vulnerable to tautomerization in its reduced form under alkaline conditions. We obtain kinetic rate constants for tautomerization by applying Bayesian inference to ultraviolet-visible spectroscopic data from operating flow cells and show that these rate constants quantitatively account for capacity fade measured in cycled cells. We use density functional theory (DFT) modeling to identify structural and chemical predictors of tautomerization resistance and demonstrate that they qualitatively explain stability trends for several commercially available and synthesized derivatives. Among these, quinoxaline-2-carboxylic acid shows a dramatic increase in stability over DMeQUIC and does not exhibit capacity fade in mixed symmetric cell cycling. The molecular design principles identified in this work set the stage for further development of quinoxalines in practical, aqueous organic RFBs.

[Efficacy of Venetoclax Plus Azacitidine in Relapsed/Refractory Acute Myeloid Leukemia Patients with FLT3-ITD Mutation].

OBJECTIVE: To explore the efficacy of venetoclax (VEN) plus azacitidine (AZA) in patients with FLT3-ITD mutated relapsed/refractory acute myeloid leukemia (FLT3-ITDmut R/R AML) and analyze the molecular genetic characteristics of the patients. METHODS: Clinical baseline characteristics and follow-up data of 16 R/R AML patients treatd with VEN plus AZA in the hematology department of Shenzhen Second People's Hospital from November 2018 to April 2021 were collected. Leukemia related genes were detected by next-generation sequencing(NGS) or PCR. The relationship between the efficacy of VEN plus AZA and molecular genetics characteristics of patients with FLT3-ITDmut R/R AML were analyzed. RESULTS: 14.3% (1/7) of the patients in FLT3-ITDmut group and 22.2% (2/9) of the patients in FLT3-ITDwt group achieved complete remission (CR)/CR with incomplete blood count recovery (CRi), respectively, with no significant difference (P=0.69). There was no significant difference in overall response rate (ORR) (CR/CRi+PR) between FLT3-ITDmut group and FLT3-ITDwt group [42.9%(3/7) vs 44.4%(4/9), P=0.95], too. The median overall survival (OS) time of FLT3-ITDmut patients was significantly shorter than that of FLT3-ITDwt patients (130 vs 300 days, respectively) (P =0.02). Co-existing mutations of FLT3-ITD and IDH1 were detected in one patient who achieved CR. Co-existing mutations of FLT3-ITD and SF3B1 were found in one patient who achieved PR. Three FLT3-ITDmut R/R AML patients accompanied with NPM1 mutation had no response to VEN plus AZA. CONCLUSION: VEN plus AZA showed a certain effect on patients with FLT3-ITDmut R/R AML. To improve OS of the patients, bridging transplantation is need. IDH1 and SF3B1 mutations might predict that patients with FLT3-ITDmut R/R AML have treatment response to VEN plus AZA, while the combination of NPM1 mutation may indicate poor response.

Understanding capacity fade in organic redox-flow batteries by combining spectroscopy with statistical inference techniques.

Organic redox-active molecules are attractive as redox-flow battery (RFB) reactants because of their low anticipated costs and widely tunable properties. Unfortunately, many lab-scale flow cells experience rapid material degradation (from chemical and electrochemical decay mechanisms) and capacity fade during cycling (>0.1%/day) hindering their commercial deployment. In this work, we combine ultraviolet-visible spectrophotometry and statistical inference techniques to elucidate the Michael attack decay mechanism for 4,5-dihydroxy-1,3-benzenedisulfonic acid (BQDS), a once-promising positive electrolyte reactant for aqueous organic redox-flow batteries. We use Bayesian inference and multivariate curve resolution on the spectroscopic data to derive uncertainty-quantified reaction orders and rates for Michael attack, estimate the spectra of intermediate species and establish a quantitative connection between molecular decay and capacity fade. Our work illustrates the promise of using statistical inference to elucidate chemical and electrochemical mechanisms of capacity fade in organic redox-flow battery together with uncertainty quantification, in flow cell-based electrochemical systems.

Efficacy of Venetoclax Plus Azacitidine in Relapsed/Refractory Acute Myeloid Leukemia Patients with FLT3-ITD Mutation / 中国实验血液学杂志

OBJECTIVE@#To explore the efficacy of venetoclax (VEN) plus azacitidine (AZA) in patients with FLT3-ITD mutated relapsed/refractory acute myeloid leukemia (FLT3-ITDmut R/R AML) and analyze the molecular genetic characteristics of the patients.@*METHODS@#Clinical baseline characteristics and follow-up data of 16 R/R AML patients treatd with VEN plus AZA in the hematology department of Shenzhen Second People's Hospital from November 2018 to April 2021 were collected. Leukemia related genes were detected by next-generation sequencing(NGS) or PCR. The relationship between the efficacy of VEN plus AZA and molecular genetics characteristics of patients with FLT3-ITDmut R/R AML were analyzed.@*RESULTS@#14.3% (1/7) of the patients in FLT3-ITDmut group and 22.2% (2/9) of the patients in FLT3-ITDwt group achieved complete remission (CR)/CR with incomplete blood count recovery (CRi), respectively, with no significant difference (P=0.69). There was no significant difference in overall response rate (ORR) (CR/CRi+PR) between FLT3-ITDmut group and FLT3-ITDwt group [42.9%(3/7) vs 44.4%(4/9), P=0.95], too. The median overall survival (OS) time of FLT3-ITDmut patients was significantly shorter than that of FLT3-ITDwt patients (130 vs 300 days, respectively) (P =0.02). Co-existing mutations of FLT3-ITD and IDH1 were detected in one patient who achieved CR. Co-existing mutations of FLT3-ITD and SF3B1 were found in one patient who achieved PR. Three FLT3-ITDmut R/R AML patients accompanied with NPM1 mutation had no response to VEN plus AZA.@*CONCLUSION@#VEN plus AZA showed a certain effect on patients with FLT3-ITDmut R/R AML. To improve OS of the patients, bridging transplantation is need. IDH1 and SF3B1 mutations might predict that patients with FLT3-ITDmut R/R AML have treatment response to VEN plus AZA, while the combination of NPM1 mutation may indicate poor response.

Stratification by Tumor Grade Groups in a Holistic Evaluation of Machine Learning for Brain Tumor Segmentation.

Accurate and consistent segmentation plays an important role in the diagnosis, treatment planning, and monitoring of both High Grade Glioma (HGG), including Glioblastoma Multiforme (GBM), and Low Grade Glioma (LGG). Accuracy of segmentation can be affected by the imaging presentation of glioma, which greatly varies between the two tumor grade groups. In recent years, researchers have used Machine Learning (ML) to segment tumor rapidly and consistently, as compared to manual segmentation. However, existing ML validation relies heavily on computing summary statistics and rarely tests the generalizability of an algorithm on clinically heterogeneous data. In this work, our goal is to investigate how to holistically evaluate the performance of ML algorithms on a brain tumor segmentation task. We address the need for rigorous evaluation of ML algorithms and present four axes of model evaluation-diagnostic performance, model confidence, robustness, and data quality. We perform a comprehensive evaluation of a glioma segmentation ML algorithm by stratifying data by specific tumor grade groups (GBM and LGG) and evaluate these algorithms on each of the four axes. The main takeaways of our work are-(1) ML algorithms need to be evaluated on out-of-distribution data to assess generalizability, reflective of tumor heterogeneity. (2) Segmentation metrics alone are limited to evaluate the errors made by ML algorithms and their describe their consequences. (3) Adoption of tools in other domains such as robustness (adversarial attacks) and model uncertainty (prediction intervals) lead to a more comprehensive performance evaluation. Such a holistic evaluation framework could shed light on an algorithm's clinical utility and help it evolve into a more clinically valuable tool.

Automated Loss-of-Balance Event Identification in Older Adults at Risk of Falls during Real-World Walking Using Wearable Inertial Measurement Units.

Loss-of-balance (LOB) events, such as trips and slips, are frequent among community-dwelling older adults and are an indicator of increased fall risk. In a preliminary study, eight community-dwelling older adults with a history of falls were asked to perform everyday tasks in the real world while donning a set of three inertial measurement sensors (IMUs) and report LOB events via a voice-recording device. Over 290 h of real-world kinematic data were collected and used to build and evaluate classification models to detect the occurrence of LOB events. Spatiotemporal gait metrics were calculated, and time stamps for when LOB events occurred were identified. Using these data and machine learning approaches, we built classifiers to detect LOB events. Through a leave-one-participant-out validation scheme, performance was assessed in terms of the area under the receiver operating characteristic curve (AUROC) and the area under the precision recall curve (AUPR). The best model achieved an AUROC ≥0.87 for every held-out participant and an AUPR 4-20 times the incidence rate of LOB events. Such models could be used to filter large datasets prior to manual classification by a trained healthcare provider. In this context, the models filtered out at least 65.7% of the data, while detecting ≥87.0% of events on average. Based on the demonstrated discriminative ability to separate LOBs and normal walking segments, such models could be applied retrospectively to track the occurrence of LOBs over an extended period of time.

[Advantages of cryopreservation technology for rare human sperm].

OBJECTIVE: To search for an effective method for cryopreservation of rare human sperm (RHS) by comparing the effect of RHS cryopreservation technology with that of conventional cryopreservation technology on post-thaw sperm from patients with severe oligozoospermia. METHODS: Semen samples obtained from 82 patients with severe oligozoospermia were preserved by RHS cryopreservation technology, and another 24 samples cryopreserved by conventional technology, the former divided into groups A (sperm concentration < 1×106/ml, n = 54) and B (1×106/ml ≤ sperm concentration < 5×106/ml, n = 28), and the latter included in group C (sperm concentration < 15×106 /ml, n = 24). The survival rate of post-thaw sperm and recovery rate of progressively motile sperm (PMS) were compared among the three groups. RESULTS: The survival rate of post-thaw sperm was significantly higher in groups A and B than in C (ï¼»62.8 ± 18.7ï¼½% and ï¼»61.9 ± 17.2ï¼½% vs ï¼»50.7 ± 13.5ï¼½%, P < 0.05), and so was the recovery rate of PMS (ï¼»68.7 ± 18.4ï¼½% and ï¼»70.7 ± 15.5ï¼½% vs ï¼»29.2 ± 12.4ï¼½% , P < 0.05), but there were no statistically significant differences between groups A and B in either of the two parameters (P > 0.05). CONCLUSIONS: The cryopreservation technology for rare human sperm may yield relatively stable post-thaw results and deserves a wide clinical application in preserving male fertility.

Advantages of cryopreservation technology for rare human sperm / 中华男科学杂志

<p><b>Objective</b>To search for an effective method for cryopreservation of rare human sperm (RHS) by comparing the effect of RHS cryopreservation technology with that of conventional cryopreservation technology on post-thaw sperm from patients with severe oligozoospermia.</p><p><b>METHODS</b>Semen samples obtained from 82 patients with severe oligozoospermia were preserved by RHS cryopreservation technology, and another 24 samples cryopreserved by conventional technology, the former divided into groups A (sperm concentration < 1×10⁶/ml, n = 54) and B (1×10⁶/ml ≤ sperm concentration < 5×10⁶/ml, n = 28), and the latter included in group C (sperm concentration < 15×106 /ml, n = 24). The survival rate of post-thaw sperm and recovery rate of progressively motile sperm (PMS) were compared among the three groups.</p><p><b>RESULTS</b>The survival rate of post-thaw sperm was significantly higher in groups A and B than in C (［62.8 ± 18.7］% and ［61.9 ± 17.2］% vs ［50.7 ± 13.5］%, P < 0.05), and so was the recovery rate of PMS (［68.7 ± 18.4］% and ［70.7 ± 15.5］% vs ［29.2 ± 12.4］% , P < 0.05), but there were no statistically significant differences between groups A and B in either of the two parameters (P > 0.05).</p><p><b>CONCLUSIONS</b>The cryopreservation technology for rare human sperm may yield relatively stable post-thaw results and deserves a wide clinical application in preserving male fertility.</p>

[Effect of Myeloma-Derived Exosomes on Surface Activating Receptors of NK Cells].

OBJECTIVE: To investigate the effect of myeloma-derived exosomes on surface activating receptors of NK cells, and to explore the mechanism of the function defect of NK cells. METHODS: The exosomes from the supernatant of multiple myeloma cell lines RPMI8226 and U266 were extracted by ultracentrifugation, and the size of them was identified under electron microscope; the human primary NK cells were extracted, and were co-cultured with the myeloma-derived exosomes (40 µg/ml), then the expression levels of surface activating receptors NKp46, NKp30 and NKG2D of NK cells at 0,1,4 and 24 hours were detected by flow cytometry. RESULTS: The exosomes showed small vesicular, sized 30-100 nm under electron microscope. The expression of surface activating receptors of NK cells declined at different degree after co-cultured with myeloma-derived exosomes. CONCLUSION: Myeloma-derived exosomes can inhibit the expression of surface activating receptors of NK cells.

Effect of Myeloma-Derived Exosomes on Surface Activating Receptors of NK Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of myeloma-derived exosomes on surface activating receptors of NK cells, and to explore the mechanism of the function defect of NK cells.</p><p><b>METHODS</b>The exosomes from the supernatant of multiple myeloma cell lines RPMI8226 and U266 were extracted by ultracentrifugation, and the size of them was identified under electron microscope; the human primary NK cells were extracted, and were co-cultured with the myeloma-derived exosomes (40 µg/ml), then the expression levels of surface activating receptors NKp46, NKp30 and NKG2D of NK cells at 0,1,4 and 24 hours were detected by flow cytometry.</p><p><b>RESULTS</b>The exosomes showed small vesicular, sized 30-100 nm under electron microscope. The expression of surface activating receptors of NK cells declined at different degree after co-cultured with myeloma-derived exosomes.</p><p><b>CONCLUSION</b>Myeloma-derived exosomes can inhibit the expression of surface activating receptors of NK cells.</p>

[Influencing factors of sperm membrane fluidity].

Sperm membrane fluidity is one of the causes of male infertility, and it is thought to be related with temperature, reactive oxygen species, oxygen free radicals, anti-sperm antibodies, stilbestrol, and fenvalerate. A deeper insight into the influencing factors of sperm membrane fluidity is of vital importance for in vitro sperm preservation, revival of frozen-thawed sperm, in vitro fertilization and management of male infertility.

Influencing factors of sperm membrane fluidity / 中华男科学杂志

Sperm membrane fluidity is one of the causes of male infertility, and it is thought to be related with temperature, reactive oxygen species, oxygen free radicals, anti-sperm antibodies, stilbestrol, and fenvalerate. A deeper insight into the influencing factors of sperm membrane fluidity is of vital importance for in vitro sperm preservation, revival of frozen-thawed sperm, in vitro fertilization and management of male infertility.

[Xianling Gubao Capsule improves semen quality].

OBJECTIVE: To observe the effect of the compound Chinese traditional drug Xianling Gubao Capsule on the semen quality of infertile males. METHODS: We treated 66 infertile men with Xianling Gubao Capsule for 24 months, and analyzed the semen quality and sperm morphology before and after the treatment. RESULTS: Two months after the medication, sperm concentration was increased by a small margin, but no statistically significant changes were observed in sperm vitality and motility (P > 0.05), the rate of morphologically normal sperm was significantly raised from 25.8% before treatment to 57.6% (P < 0.05) in those with the normal rate > or = 15%, but decreased from 53.0% to 25.8% (P < 0.05) in those with the normal rate < 9%. Among the 7 cases of oligospermia, the rate of morphologically normal sperm was elevated to an average of 10.9% after the 4-month medication, significantly different from the baseline rate of 5.8% (P < 0.05). Five spontaneous pregnancies and 1 successful IVF-ICSI were achieved during the treatment. CONCLUSION: Xianling Gubao Capsule can improve semen quality and significantly increase the percentage of morphologically normal sperm.

Xianling Gubao Capsule improves semen quality / 中华男科学杂志

<p><b>OBJECTIVE</b>To observe the effect of the compound Chinese traditional drug Xianling Gubao Capsule on the semen quality of infertile males.</p><p><b>METHODS</b>We treated 66 infertile men with Xianling Gubao Capsule for 24 months, and analyzed the semen quality and sperm morphology before and after the treatment.</p><p><b>RESULTS</b>Two months after the medication, sperm concentration was increased by a small margin, but no statistically significant changes were observed in sperm vitality and motility (P > 0.05), the rate of morphologically normal sperm was significantly raised from 25.8% before treatment to 57.6% (P < 0.05) in those with the normal rate > or = 15%, but decreased from 53.0% to 25.8% (P < 0.05) in those with the normal rate < 9%. Among the 7 cases of oligospermia, the rate of morphologically normal sperm was elevated to an average of 10.9% after the 4-month medication, significantly different from the baseline rate of 5.8% (P < 0.05). Five spontaneous pregnancies and 1 successful IVF-ICSI were achieved during the treatment.</p><p><b>CONCLUSION</b>Xianling Gubao Capsule can improve semen quality and significantly increase the percentage of morphologically normal sperm.</p>

[Influence of cryoprotectant with glycerol and freezing-thawing procedure on the motility of human sperm].

OBJECTIVE: To investigate the effects of cryoprotectant with glycerol and the freezing-thawing procedure on the motility of METHODS: The motion characteristics of human sperm from 18 selected specimens were assessed by computer-assisted human sperm. sperm analysis before and after adding hyper-osmolarity cryoprotectant with glycerol and the freeze-thaw procedure, and the data were evaluated in pairs. RESULTS: The adding of cryoprotectant caused an increase in the proportion of rapid linear motile sperms (P < 0.05) and sperm velocities, including VCL, VSL and VAP (P < 0.005). But no changes were observed in the proportion of progressively motile sperms and sperm motility. Compared with the data from pre-frozen samples, velocities of post-thawed sperms and the percentage of motile sperms in each grade significantly declined (P < or = 0.01), so did ALH, while WOB, LIN and STR remained unchanged (P > 0.05). Significant differences in ALH, WOB, LIN and STR were observed only in comparison between the post-thawed and pre-treated samples. CONCLUSION: The number of Grade a sperms and sperm velocity increased after adding hyper-osmolarity cryoprotectant with glycerol. The sperm motile potential was impaired and even entirely destroyed in some cases by cryodamage. The influences on the sperm motion were differently induced in freezing-thawing procedures.

[Semen quality and sperm morphologic study of infertile men with varicocele].

OBJECTIVE: To examine the semen quality and the sperm morphology in infertile men with varicocele. METHODS: Semen from 98 infertile men with varicocele were studied and those of 130 normal semen donors were taken as the control. Semen analysis was performed based on the methods described in the WHO manual and sperm morphology was evaluated by WHO criteria. RESULTS: A significantly reduced percentage of normal morphologic sperm and of forward progression were found in patients with varicocele comparing with those of the control (P <0.001). The head defects were observed as the predominant type of sperm malformation. CONCLUSION: The varicocele increases malformed sperm in ejaculates, which may result from impaired male fertility by varicocele. Sperm morphologic assessment with WHO criteria provides a sensitive and practical measurement of sperm damage in infertile men with varicocele.

Semen quality and sperm morphologic study of infertile men with varicocele / 中华男科学杂志

<p><b>OBJECTIVE</b>To examine the semen quality and the sperm morphology in infertile men with varicocele.</p><p><b>METHODS</b>Semen from 98 infertile men with varicocele were studied and those of 130 normal semen donors were taken as the control. Semen analysis was performed based on the methods described in the WHO manual and sperm morphology was evaluated by WHO criteria.</p><p><b>RESULTS</b>A significantly reduced percentage of normal morphologic sperm and of forward progression were found in patients with varicocele comparing with those of the control (P <0.001). The head defects were observed as the predominant type of sperm malformation.</p><p><b>CONCLUSION</b>The varicocele increases malformed sperm in ejaculates, which may result from impaired male fertility by varicocele. Sperm morphologic assessment with WHO criteria provides a sensitive and practical measurement of sperm damage in infertile men with varicocele.</p>

Influence of cryoprotectant with glycerol and freezing-thawing procedure on the motility of human sperm / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of cryoprotectant with glycerol and the freezing-thawing procedure on the motility of</p><p><b>METHODS</b>The motion characteristics of human sperm from 18 selected specimens were assessed by computer-assisted human sperm. sperm analysis before and after adding hyper-osmolarity cryoprotectant with glycerol and the freeze-thaw procedure, and the data were evaluated in pairs.</p><p><b>RESULTS</b>The adding of cryoprotectant caused an increase in the proportion of rapid linear motile sperms (P < 0.05) and sperm velocities, including VCL, VSL and VAP (P < 0.005). But no changes were observed in the proportion of progressively motile sperms and sperm motility. Compared with the data from pre-frozen samples, velocities of post-thawed sperms and the percentage of motile sperms in each grade significantly declined (P < or = 0.01), so did ALH, while WOB, LIN and STR remained unchanged (P > 0.05). Significant differences in ALH, WOB, LIN and STR were observed only in comparison between the post-thawed and pre-treated samples.</p><p><b>CONCLUSION</b>The number of Grade a sperms and sperm velocity increased after adding hyper-osmolarity cryoprotectant with glycerol. The sperm motile potential was impaired and even entirely destroyed in some cases by cryodamage. The influences on the sperm motion were differently induced in freezing-thawing procedures.</p>

Characteristics of human semen by microscopic observation during liquefaction / 中华检验医学杂志

Objective To compaire the physical characteristics of semen morphology before and after semen coagulation-liquefaction under microscope and understand the significance of these characteristics for the determination of semen liquefaction.Methods Semens were placed in sperm counting chamber immediately after collection.The morphological changes of the seminal gelatinous substance during liquefaction were observed under microscope and analyzed.Results Morphological changes during semen liquefaction can be clearly observed.Among 32 samples of semen,forward sperm progression and motility were (30.3?12.4)% and (45.0?14.9)%,(44.9?12.7)% and (59.0?15.3)%,before and after the liquefaction,respectively.The differences were statistically significant (t=-1.130,5.023,P0.05).Conclusions Microscopic observation of the seminal gelatinous substance is a simple and feasible method for objective measurement of sperm liquefaction.These findings suggest it may provide pathological significance on semen liquefaction abnormality in infertility clinic.