As the chemical environment of semen can have a profound effect on sperm quality, we examined the effect of pH on the motility, viability and capacitation of human sperm. The sperm in this study was ...collected from healthy males to avoid interference from other factors. The spermatozoa cultured in sperm nutrition solution at pH 5.2, 6.2, 7.2 and 8.2 were analyzed for sperm total motility, progressive motility (PR), hypo-osmotic swelling (HOS) rate, and sperm penetration. Our results showed that these parameters were similar in pH 7.2 and 8.2 sperm nutrition solutions, but decreased in pH 5.2 and 6.2 solutions. The HOS rate exhibited positive correlation with the sperm total motility and PR. In addition, the sperm Na(+)/K(+)-ATPase activity at different pHs was measured, and the enzyme activity was significantly lower in pH 5.2 and 6.2 media, comparing with that in pH 8.2 and pH 7.2 solutions. Using flow cytometry (FCM) and laser confocal scanning microscopy (LCSM) analysis, the intracellular Ca2(+ )concentrations of sperm cultured in sperm capacitation solution at pH 5.2, 6.2, 7.2 and 8.2 were determined. Compared with that at pH 7.2, the mean fluorescence intensity of sperm in pH 5.2 and 6.2 media decreased significantly, while that of pH 8.2 group showed no difference. Our results suggested that the declined Na(+)/K(+)-ATPase activity at acidic pHs result in decreased sperm movement and capacitation, which could be one of the mechanisms of male infertility.
To understand the growth mechanism of pyrolytic graphite on ideal graphite substrate by chemical vapor deposition (CVD), the process simulated by molecular dynamics is performed. The simulation ...revealed that only an amorphous graphite-like membrane (a-GLM) can be obtained using the Tersoff potential function. It is revealed that the formation process for the first layer of the a-GLM initiates from the firstly deposited carbon monomers, dimers, and trimers as growth points, on which Y-shaped long chain is formed, and then the network with pores are developed, and finally the graphene-like layer with six-membered dominated rings appears after repair treatment. The following deposition simulation for more deposited carbon atoms indicates that a second layer like-graphene is more prone to superpose onto the microdomains of the first layer like-graphene until the formation of the island-like bumps, and the concave zone around the bumps will be filled by deposited atoms and modified by defect repair. The growth mechanism for pyrolytic graphite prepared by CVD can be deduced by the simulation inspiration. The optimal deposition temperature of 2400 K is acquired by evaluating the integrity of the first deposited graphene film by statistics of five-to-seven-membered carbon ring number. This study can provide theoretical references for the design of the pyrolytic graphite production process.
To understand the growth mechanism of pyrolytic graphite on ideal graphite substrate by chemical vapor deposition (CVD), the process simulated by molecular dynamics is performed.
Objective:
Our study aims to assess the effectiveness and safety profile of Disitamab Vedotin (DV, RC48-ADC), an innovative humanized anti-HER2 antibody conjugated with tubulin-disrupting antimitotic ...drug monomethyl auristatin E (MMAE) via a cleavable peptide linker. This treatment combined immune checkpoint inhibitors as part of the bladder sparing approach for selected patients suffering from locally and locally advanced bladder urothelial carcinoma.
Patients and methods:
We conducted a two-center, real-world study involving locally advanced urothelial carcinoma (UC) patients. Patients were classified based on HER2 expression (IHC 3+/2+/1+) or lack of HER2 expression (IHC 0). The primary endpoint was the objective response rate (ORR), assessed by the investigator following the criteria of RECIST V1.1. Secondary endpoints encompassed the pathological complete response rate (pCR), pathological partial response rate (pPR), and pathological stable disease (pSD), along with recurrence-free survival (RFS), the pathological downstaging rate, and the safety profile of the treatment.
Results:
In this study, nine patients were enrolled, with a median follow-up duration of 12.0 months. The overall confirmed ORR was 88.9%, Five patients achieved a complete response (CR), and three patients achieved a partial response (PR). The radiological complete response (rCR) aligned perfectly with pCR. The median radiological progression-free survival (rPFS) spanned 12.0 months (range from 8.0 to 17.0 months). One patient diagnosed with disease progression (PD) underwent a radical cystectomy. The pathological stage evolved from T2N0M0 to T3aN2M0, followed by adjuvant chemotherapy with a gemcitabine-cisplatin (GC) combination radiotherapy. At the 9-month follow-up, neither recurrence nor metastasis was observed. The rate and intensity of complications were manageable among these patients, with no evidence of grade 4 and 5 adverse events.
Conclusion:
The combination of DV and PD-1 demonstrated considerable activity in the objective response rate (ORR) in patients with HER2 IHC 0/1+/2+/3+ muscle-invasive bladder cancer (MIBC), along with the longest reported median radiological progression-free survival (rPFS) to date. With an extended duration of treatment, the safety profile of DV plus PD-1 was also confirmed to be manageable.
Abstract
Tetraselmis helgolandica
var. Tsingtaoensis is a marine microalga. It can produce a large amount of starch, especially amylose, with addition of carbon source and specific circadian rhythm. ...The mechanism behind this phenomenon is still unclear. Analysis of this mechanism can help to develop
T. helgolandica
into a new green bioengineering chassis organism. We explained how circadian rhythm and glucose affect the rate of starch accumulation and starch structure in
T. helgolandica
based on the transcriptome. The glucose inhibited the photosynthetic system of
T. helgolandica
, while the circadian rhythm can alleviate the inhibition. Circadian rhythm induced the upregulation of Embden–Meyerhof–Parnas pathway and pentose phosphate pathway (PPP) in
T. helgolandica
, but had little effect on the tricarboxylic acid cycle. PPP pathway provides Ribulose‐1,5‐bisphosphate, which may be beneficial for dark reactions and nucleotide synthesis. And PPP pathway provides Nicotinamide adenine dinucleotide phosphate, which facilitates energy substance synthesis. This will further upregulate the starch metabolic pathway. The transcript level of the key gene ADP‐Glucose pyrophosphorylase is mainly regulated by glucose. The granule‐bound starch synthase (
gbss
), a key gene for amylose synthesis, is mainly influenced by circadian rhythm. In general, the increase of starch synthesis and amylose ratio requires both glucose addition and circadian rhythm. We report the first referenced transcriptome of
T. helgolandica
. Differences between transcripts reveal how circadian rhythm and glucose addition affected the rate of starch synthesis and structural variation. It provides a reference for an in‐depth study of starch synthesis in green algae.
The herniation of ureter is rare. A 59-year-old woman with hydronephrosis caused by herniation of ureter through psoas muscle fascia was observed. The patient referred to our clinic with four weeks' ...history of left flank pain and fever. Computed tomography urography and antegrade combined with retrograde urography revealed tortuous and proximal dilated ureter and hydronephrosis on the left side. Herniation of ureter through psoas muscle fascia was confirmed in operation and laparoscopic ureteroplasty with end to end anastomosis was done. No obvious hydronephrosis or flank pain was observed in follow-up for one and a half year.
Elevated plasma gonadotropins were associated with desensitization of Sertoli and Leydig cells in the male testis. Testis spermatogenesis ability would be improved via inhibiting high endogenous ...gonadotropin in patients with severe oligozoospermia. Whether it would be beneficial for non-obstructive azoospermia (NOA) patients was still unclear.
Goserelin, a gonadotropin releasing hormone agonist (GnRHα) was used to suppress endogenous gonadotropin levels (gonadotropin reset) in the NOA patients, improving the sensitization of the Sertoli and Leydig cells. Then human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) were injected to stimulate them to ameliorate the ability of testicular spermatogenesis. The main outcome measure was the existence of spermatozoa in the semen or by testicular sperm extraction (TESE). Elevation of inhibin B and/or ameliorative expression pattern of ZO-1 was the secondary objective.
A total of 35 NOA men who failed to retrieve sperm via TESE were enrolled. Among these, 10 patients without treatment were selected as control group and secondary TESE was performed 6 months later. Of the 25 treated men, inhibin B was elevated in 11 patients in the first 4 weeks (Response group), while only 5 patients had constant increase in the following 20 weeks (Response group 2). Of the 5 men, 2 men acquired sperm (Response group 2B), while 3 failed (Response group 2A). Immunofluorescence of mouse vasa homologue (MVH) and ZO-1 showed that both positive MVH signals and ZO-1 expression were significantly increased in the Response group 2, but only Response group 2B showed ameliorative ZO-1 distribution.
Gonadotropin reset, a new therapeutic protocol with GnRHα, was able to improve the ability of testicular spermatogenesis in the NOA patients through restoring the sensitivity of Sertoli and Leydig cells, which were reflected by elevated inhibin B and ameliorative ZO-1 expression and distribution.
ClinicalTrials.gov identifier: NCT02544191 .
This study aimed to evaluate the awareness rate of prostate-specific antigen (PSA) among the general public in China and provide data about prostate cancer (PCa) for related scientific research.
A ...cross-sectional survey of PSA awareness was conducted in multiple regional populations using an online questionnaire. The questionnaire included basic information, knowledge about PCa, the awareness rate and application of PSA, and future expectations toward applying PSA screening in clinical practice. The study applied the methods of Pearson chi-square analysis and Logistic regression analysis.
A total of 493 valid questionnaires were included. Two hundred and nineteen respondents (44.4%) were males, and 274 (55.6%) were females. Of all respondents, 212 (43.0%) were under 20 years old, 147 (29.8%) were 20-30 years old, 74 (15.0%) were 30-40 years old, and 60 (12.2%) were over 40 years old. There are 310 people (62.9%) with medical educational background and 183 (37.1%) without. One hundred eighty-seven (37.9%) of the respondents were aware of PSA, and 306 (62.1%) were unaware of PSA. Statistically significant differences were obtained between the two groups regarding different ages, educational backgrounds, occupations, departments, and habits of knowing medical knowledge (all
< 0.05). In addition, the differences between the group of aware of PSA (AP) and the group unaware of PSA (UAP) in terms of whether they had been exposed to PSA screening and whether they had exposure to PCa patients or related knowledge were also observed (all
< 0.05). Age ≥30 years, medical educational background, understanding of medical knowledge, exposure to PCa patients or related knowledge, exposure to PSA screening, and status as a graduate student and above were independent factors for the occurrence of PSA awareness events (all
< 0.05). In addition, age ≥ 30 years, medical educational background, and awareness of PSA were independent factors for future expectations toward PSA (all
< 0.05).
We first analyzed the public awareness of PSA. Cognition degrees of PSA and PCa awareness vary among different populations in China. Therefore, we should designate corresponding widespread scientific educational programs for different populations to increase the awareness rate of PSA.
•Multi-scale interface-vortex interaction of jet in crossflow is reported by AMR-VOF.•KH induced bag breakup and RT/surface-thinning induced surface breakup are revealed.•Vorticity concentrates near ...large deformed interface, perpendicular to its normal.•Droplet size exhibits a log-normal distribution while bag breakup has a bimodal tend.•Key parameters for the empirical correlation of jet trajectory are verified.
In this paper, a detailed numerical simulation of liquid jet atomization in crossflow is performed based on the volume of fluid method coupled with the adaptive mesh refinement technique. The multi-scale phase interface evolution and the interface-vortex interaction are reported. It is found that the momentum flux ratio, Weber number, density ratio and viscosity ratio are key variables for the empirical correlation to accurately predict the atomization characteristics. Three breakup regimes, i.e., column bag breakup, surface breakup and ligament breakup, occur due to the great mass and momentum exchanges at the interface. Specially, the Kelvin-Helmholtz instability induces axial surface waves that eventually develop into column bag breakup while the Rayleigh-Taylor instability and surface thinning can induce surface breakup. Relatively, the column bag breakup generates larger liquid structures, presenting a bimodal feature. The produced ligaments either shrink to droplets or further breakup into droplets depending on their size and shape, leading to a log-normal distribution of droplet size. The interface-vortex interaction is distinctive compared to single-phase flows. A vortex core is observed to simultaneously form, grow and dissipate within each bag during the life circle of the bag, and three types of counter-rotating vortex pair exist around the column root, bag membrane and liquid droplets. Vortical structures tend to concentrate near the interface with large deformations, possessing a strong perpendicularity between the phase interface and the vortex. This work offers fundamental basis for better understanding and organization of atomization.
Bladder cancer is a common malignancy in the urinary system. Defects of drug molecules in bladder during treatment, such as passive diffusion, rapid clearance of periodic urination, poor adhesion and ...permeation abilities, lead to low delivery efficiency of conventional drugs and high recurrence rate of disease. In this study, we designed multi‐responsive mesoporous polydopamine (PDA) composite nanorods cooperating with nano‐enzyme and photosensitiser for intensive immunotherapy of bladder cancer. The strongly adhesive mesoporous PDA with wheat germ agglutinin on nanoparticles could specifically adhere to epithelial glycocalyx and made the nanoparticles aggregate in urinary pathways. Meanwhile, 2,3‐dimethylmaleic anhydride could be hydrolysed in acidic conditions of tumour microenvironment, giving it a positive charge (charge reversal), which is more amenable to enter cancer cells. Afterwards, manganese dioxide nanorods could catalyse the reaction of excess H2O2 in tumour microenvironment to generate active oxygen, so as to change the hypoxic environment in tumour, and achieve a pH‐responsive for slow release of PD‐L1. After the ICG was irradiated by infrared light, a large amount of singlet oxygen was generated, thereby enhancing the therapeutic effect and reducing toxicity in vivo. Besides, mesoporous PDA with indocyanine green photothermal agent could have a local heat up quickly under the near‐infrared light to kill cancer cells, thereby enhancing therapeutic efficacy. Accordingly, this mesoporous PDA composite nanorods shed a light on bladder tumour treatment.
In this study, we found a mesoporous PDA composite nanorods with dual responses of photothermal and immune for the treatment of bladder cancer. The nanorods work with wheat germ agglutinin to specifically adhere to the superior calyx in the urinary system. Through photothermal pH response and other ways, the nanorods exert killing effect on cancer cells.
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