Natural course of metastatic castration-resistant prostate cancer in the era of intensified androgen deprivation therapy in the hormone-sensitive setting.

BACKGROUND: Androgen deprivation therapy (ADT) intensification (ADTi) (i.e., ADT with androgen receptor pathway inhibitor or docetaxel, or both) has significantly improved survival outcomes of patients with metastatic hormone-sensitive prostate cancer (mHSPC). However, the impact of prior ADTi in the mHSPC setting on the disease presentation and survival outcomes in metastatic castration-resistant prostate cancer (mCRPC) is not well characterized. In this study, our objective was to compare the disease characteristics and survival outcomes of patients with new mCRPC with respect to receipt of intensified or nonintensified ADT in the mHSPC setting. METHODS: In this institutional review board-approved retrospective study, eligibility criteria were as follows: patients diagnosed with mCRPC, treated with an approved first-line mCRPC therapy, and who received either intensified or nonintensified ADT in the mHSPC setting. Progression-free survival (PFS) was defined from the start of first-line therapy for mCRPC to progression per Prostate Cancer Working Group 2 criteria or death, and overall survival (OS) was defined from the start of first-line therapy for mCRPC to death or censored at the last follow-up. A multivariable analysis using the Cox proportional hazards model was used, adjusting for potential confounders. RESULTS: Patients (n = 387) treated between March 20, 2008, and August 18, 2022, were eligible and included: 283 received nonintensified ADT, whereas 104 were treated with ADTi. At mCRPC diagnosis, patients in the ADTi group were significantly younger, had more visceral metastasis, lower baseline prostate-specific antigen (all p < 0.01), and lower hemoglobin (p = 0.027). Furthermore, they had significantly shorter PFS (median 4.8 vs. 8.4 months, adjusted hazard ratio [HR]: 1.46, 95% confidence interval [95% CI]: 1.07-2, p = 0.017) and OS (median 21.3 vs. 33.1 months, adjusted HR: 1.53, 95% CI: 1.06-2.21, p = 0.022) compared to patients in the nonintensified ADT group. CONCLUSION: Patients treated with ADTi in the mHSPC setting and experiencing disease progression to mCRPC had more aggressive disease features of mCRPC (characterized by a higher number of poor prognostic factors at mCRPC presentation). They also had shorter PFS on first-line mCRPC treatment and shorter OS after the onset of mCRPC compared to those not receiving ADTi in the mHSPC setting. Upon external validation, these findings may impact patient counseling, prognostication, treatment selection, and design of future clinical trials in the mCRPC setting. There remains an unmet need to develop novel life-prolonging therapies with new mechanisms of action to improve mCRPC prognosis in the current era.

Neural signatures of syntactic variation in speech planning.

Planning to speak is a challenge for the brain, and the challenge varies between and within languages. Yet, little is known about how neural processes react to these variable challenges beyond the planning of individual words. Here, we examine how fundamental differences in syntax shape the time course of sentence planning. Most languages treat alike (i.e., align with each other) the 2 uses of a word like "gardener" in "the gardener crouched" and in "the gardener planted trees." A minority keeps these formally distinct by adding special marking in 1 case, and some languages display both aligned and nonaligned expressions. Exploiting such a contrast in Hindi, we used electroencephalography (EEG) and eye tracking to suggest that this difference is associated with distinct patterns of neural processing and gaze behavior during early planning stages, preceding phonological word form preparation. Planning sentences with aligned expressions induces larger synchronization in the theta frequency band, suggesting higher working memory engagement, and more visual attention to agents than planning nonaligned sentences, suggesting delayed commitment to the relational details of the event. Furthermore, plain, unmarked expressions are associated with larger desynchronization in the alpha band than expressions with special markers, suggesting more engagement in information processing to keep overlapping structures distinct during planning. Our findings contrast with the observation that the form of aligned expressions is simpler, and they suggest that the global preference for alignment is driven not by its neurophysiological effect on sentence planning but by other sources, possibly by aspects of production flexibility and fluency or by sentence comprehension. This challenges current theories on how production and comprehension may affect the evolution and distribution of syntactic variants in the world's languages.

Effect of Mixed Morphology (Simple Cubic, Face-Centered Cubic, and Body-Centered Cubic)-Based Electrodes on the Electric Double Layer Capacitance of Supercapacitors.

Supercapacitors store energy due to the formation of an electric double layer (EDL) at the interface of the electrodes and electrolyte. The present article deals with the finite element study of equilibrium electric double layer capacitance (EDLC) in the mixed morphology electrodes comprising all three fundamental crystal structures, simple cubic (SC), body-centered cubic (BCC), and face-centered cubic morphologies (FCC). Mesoporous-activated carbon forms the electrode in the supercapacitor with (C2H5)4NBF4/propylene carbonate organic electrolyte. Electrochemical interference is clearly demonstrated in the supercapacitors with the formation of the potential bands, as in the case of interference theory due to the increasing packing factor. The effects of electrode thickness varying from a wide range of 50 nm to 0.04 mm on specific EDLC have been discussed in detail. The interfacial geometry of the unit cell in contact with the electrolyte is the most important parameter determining the properties of the EDL. The critical thickness of the electrodes is 1.71 µm in all the morphologies. Polarization increases the interfacial potential and leads to EDL formation. The Stern layer specific capacitance is 167.6 µF cm-2 in all the morphologies. The maximum capacitance is in the decreasing order of interfacial geometry, as FCC > BCC > SC, dependent on the packing factor. The minimum transmittance in all the morphologies is 98.35%, with the constant figure of merit at higher electrode thickness having applications in the chip interconnects. The transient analysis shows that the interfacial current decreases with increasing polarization in the EDL. The capacitance also decreases with the increase of the scan rate.

Clinical outcomes of vitrified-warmed autologous oocyte cycles with 15-year follow-up at a single UK centre: consistent and predictable results.

RESEARCH QUESTION: What were the clinical outcomes from 332 autologous vitrified- warmed oocyte cycles derived from 3182 elective autologous oocyte freeze cycles carried out between 2008 and 2022 in a single-centre series? DESIGN: In this retrospective observational study, outcomes in 299 patients returning to use their frozen oocytes between 2015 and 2023 were analysed. RESULTS: A total of 3328 elective oocyte vitrification cycles were performed in 2280 patients. The return rate to use oocytes was 14% (299/2171). Mean ages were 37.6 years at storage and 40 at warming. Ninety-three clinical pregnancies and 77 healthy live births were recorded. The live birth rate (LBR) was 24% (39/163) per fresh transfer and 17% (39/227) per embryo transferred. Stratified by age at freezing, the LBR per embryo transferred was 26% (12/47) in participants under 35 years, 20% (24/118) in those 35-39 years and 5% (3/62) in those 40+ years. Frozen embryo transfers (FET) achieved a 30% (24/80) LBR per embryo transfer and a 27% (24/90) LBR per embryo transferred. PGT-A for embryo selection doubled the LBR compared with FET from an untested embryo after one attempt (40% versus 21%). In patients aged over 40 years, the cumulative LBR reached 42% per patient in euploid FET. CONCLUSION: The proportion of patients who returned to use their stored oocytes and the clinical outcomes were consistent with other recent reports and challenges the prevalent critical narrative regarding elective oocyte freezing for fertility preservation. The results are now comparable to routine IVF. Not everyone who returns to use their oocytes will conceive, but for those choosing to preserve their fertility, oocyte freezing can provide reproducible and reassuring results.

Base-Promoted Synthesis of S-Arylisothiazolones via Intramolecular Dehydrative Cyclization of α-Keto-N-acylsulfoximines.

A base (Et3N)-promoted synthesis of 1,4-diarylisothiazolones from α-keto-N-acylsulfoximines has been achieved. The reaction proceeds via α-hydrogen abstraction from sulfoximine, followed by an intramolecular nucleophilic attack at the keto carbonyl to form a tert-hydroxy isothiazolone intermediate. The 1,4-substituted isothiazolone is obtained after dehydration via an E1cB path. This one-pot synthesis of isothiazolinones has a broad substrate scope, has a high atom economy, and provides products with good yields. The ΔELUMO-HOMO is calculated using Gaussian 16 at the B3LYP/6-31G(d,p) level of theory.

Iodine-Promoted Sulfoximidation of Cinnamic Acids via Oxidative C═C Bond Cleavage.

An iodine-promoted C═C bond cleavage with concomitant decarboxylation and cross-coupling between cinnamic acids and NH-sulfoximines has been developed. This reaction proceeds via selective C═C bond cleavage, followed by decarboxylation and oxidative sulfoximidation. This metal- and base-free protocol involves dioxygen as the source of oxygen, which is facilitated by tert-butyl hydroperoxide (TBHP) as the oxidant affording N-aroylated sulfoximines with good functional group tolerance and good yields.

PIDA/I2-mediated photo-induced aerobic N-acylation of sulfoximines with methylarenes.

A visible-light-promoted, PIDA/I2-mediated acylation of NH-sulfoximines with methylarenes as an acyl source has been achieved. This transition metal and photosensitizer-free approach provides easy access to N-acylsulfoximines via oxidative coupling of sulfoximines with easily available methylarenes without using any peroxide source. Mechanistic investigations suggest the intermediacy of radicals and the importance of molecular oxygen.

Novel MECP2 gene therapy is effective in a multicenter study using two mouse models of Rett syndrome and is safe in non-human primates.

The AAV9 gene therapy vector presented in this study is safe in mice and non-human primates and highly efficacious without causing overexpression toxicity, a major challenge for clinical translation of Rett syndrome gene therapy vectors to date. Our team designed a new truncated methyl-CpG-binding protein 2 (MECP2) promoter allowing widespread expression of MECP2 in mice and non-human primates after a single injection into the cerebrospinal fluid without causing overexpression symptoms up to 18 months after injection. Additionally, this new vector is highly efficacious at lower doses compared with previous constructs as demonstrated in extensive efficacy studies performed by two independent laboratories in two different Rett syndrome mouse models carrying either a knockout or one of the most frequent human mutations of Mecp2. Overall, data from this multicenter study highlight the efficacy and safety of this gene therapy construct, making it a promising candidate for first-in-human studies to treat Rett syndrome.

Plasma Virome of HIV-infected Subjects on Suppressive Antiretroviral Therapy Reveals Association of Differentially Abundant Viruses with Distinct T-cell Phenotypes and Inflammation.

Background: The plasma virome represents the overall composition of viral sequences present in it. Alteration in plasma virome has been reported in treatment naïve and immunocompromised (CD4 count < 200) people with HIV (PWH). However, the effect of ART on virome composition in PWH on ART with preserved CD4 counts is poorly understood. Objectives: We aimed to assess the alterations in plasma virome in PWH on ART in comparison to HIV-negative uninfected controls and to further investigate possible associations of plasma viruses with inflammation and immune dysfunction, namely, immunosenescence and immune exhaustion. Methods: Plasma viral DNA from PWH on ART and controls was used for sequencing on the Illumina Nextseq500 platform, followed by the identification of viral sequences using an automated pipeline, VIROMATCH. Multiplex cytokine assay was performed to measure the concentrations of various cytokines in plasma. Immunophenotyping was performed on PBMCs to identify T cell markers of immunosenescence and immune exhaustion. Results: In our observational, cross-sectional pilot study, chronically infected PWH on ART had significantly different viral species compositions compared to controls. The plasma virome of PWH showed a significantly high relative abundance of species Human gammaherpesvirus 4, also known as Epstein-Barr virus (EBV). Moreover, EBV emerged as a significant viral taxon differentially enriched in PWH on ART, which further correlated positively with the exhaustion phenotype of T cells and significantly increased TNF-α in PWH on ART. Additionally, a significantly increased proportion of senescent T cells and IL-8 cytokine was detected in PWH on ART. Conclusion: Altered plasma virome influenced the inflammatory response and T-cell phenotype in PWH on ART.

Inter-species interaction of bradyrhizobia affects their colonization and plant growth promotion in Arachis hypogaea.

Bradyrhizobia are the principal symbiotic partner of the leguminous plant and take active part in biological nitrogen-fixation. The present investigation explores the underlying competition among different strains during colonization in host roots. Six distinct GFP and RFP-tagged Bradyrhizobium strains were engineered to track them inside the peanut roots either independently or in combination. The Bradyrhizobium strains require different time-spans ranging from 4 to 21 days post-infection (dpi) for successful colonization which further varies in presence of another strain. While most of the individual strains enhanced the shoot and root dry weight, number of nodules, and nitrogen fixation capabilities of the host plants, no significant enhancement of plant growth and nodulation efficiency was observed when they were allowed to colonize in combinations. However, if among the combinations one strains is SEMIA 6144, the co-infection results in higher growth and nodulation efficiency of the hosts. From the competition experiments it has been found that Bradyrhizobium japonicum SEMIA 6144 was found to be the most dominant strain for effective nodulation in peanut. The extent of biofilm and exopolysaccharide (EPS) production by these isolates, individually or in combinations, were envisaged to correlate whether these parameters have any impact on the symbiotic association. But the extent of colonization, growth-promotion and nitrogen-fixation ability drastically lowered when a strain present together with other Bradyrhizobium strain. Therefore, it is imperative to understand the interaction between two co-inoculating Bradyrhizobium species for nodulation followed by plant growth promotion to develop suitable consortia for enhancing BNF in peanut and possibly for other legumes.

Impact of androgen receptor alterations on cell-free DNA genomic profiling on survival outcomes in metastatic castration-resistant prostate cancer.

BACKGROUND: Androgen receptor (AR) gene alterations, as detected by circulating tumor cell-free DNA (cfDNA) genomic profiling, have been shown to emerge after a variable duration of androgen signaling inhibition. AR alterations were associated with inferior outcomes on treatment with androgen receptor pathway inhibitors (ARPI) in the first line metastatic castration-resistant prostate cancer (mCRPC) setting in a phase 2 trial. Here in, we assessed the impact of these AR alterations on survival outcomes in a real-world patient population of mCRPC experiencing disease progression on an ARPI. METHODS: In this IRB-approved retrospective study, consecutively seen patients with a confirmed diagnosis of mCRPC, with disease progression on a treatment with ARPIs in the first line mCRPC setting, with no prior exposure to an ARPI in the castration sensitive setting, and with available cfDNA profiling from a CLIA certified laboratory were included. Patients were categorized based on AR status: wild-type (ARwt ) or alteration-positive (AR+ ). The objective was to correlate overall survival (OS) after disease progression on the first-line ARPI with the presence or absence of AR alterations. Kaplan-Meier and Cox Regression Tests were used as implemented in R-Studio (v.4.2). RESULTS: A total of 137 mCRPC patients were eligible: 69 with ARwt versus 68 with AR+ . The median OS posttreatment with the first ARPI was significantly higher for ARwt than AR+ patients (30.1 vs. 15.2 mos; p < 0.001). Of 108 patients who received a subsequent line of therapy, 63 received an alternate ARPI (AR+ 39 vs. 24 ARwt ), while 20 received a taxane-based therapy (11 AR+ vs. 9 ARwt ). Among patients receiving an alternate ARPI, AR+ had numerically shorter OS (16.8 vs. 30.4 mos, p = 0.1). Among patients receiving taxane-based regimens, the OS was not significantly different between AR+ and ARwt (14.5 vs. 10.1 mos, p = 0.18). CONCLUSION: In this real-world study, mCRPC patients with AR alterations on cfDNA had inferior OS after disease progression on the first ARPI, compared to those who did not, and may impact outcomes on a subsequent ARPI but not on subsequent taxane-based therapy received. By providing survival estimates for patients with or without AR alterations, our data may aid in patient counseling, prognostication, treatment decision, and for designing future clinical trials in this setting.

Diversity-Oriented Synthesis of Benzo[f][1,4]oxazepine-, 2H-Chromene-, and 1,2-Dihydroquinoline-Fused Polycyclic Nitrogen Heterocycles under Microwave-Assisted Conditions.

An efficient, diversity-oriented synthesis of oxazepino[5,4-b]quinazolin-9-ones, 6H-chromeno[4,3-b]quinolines, and dibenzo[b,h][1,6]naphthyridines was established involving a substrate-based approach under microwave-assisted and conventional heating conditions in high yields (up to 88%). The CuBr2-catalyzed, chemoselective cascade annulation of O-propargylated 2-hydroxybenzaldehydes and 2-aminobenzamides delivered oxazepino[5,4-b]quinazolin-9-ones involving a 6-exo-trig cyclization-air oxidation-1,3-proton shift-7-exo-dig cyclization sequence. This one-pot process showed excellent atom economy (-H2O) and constructed two new heterocyclic rings (six- and seven-membered) and three new C-N bonds in a single synthetic operation. On the other side of diversification, the reaction between O/N-propargylated 2-hydroxy/aminobenzaldehydes and 2-aminobenzyl alcohols delivered 6H-chromeno[4,3-b]quinolines and dibenzo[b,h][1,6]naphthyridines involving sequential imine formation-[4 + 2] hetero-Diels-Alder reaction-aromatization steps. The influence of microwave assistance was superior to conventional heating, where the reactions were clean, rapid, and completed in 15 min, and the conventional heating required a longer reaction time at a relatively elevated temperature.

Effect of simple cubic, face-centered cubic, and body-centered cubic-electrodes on the electric double layer capacitance of supercapacitors.

The continuum theory has been used to analyze the polarization, ion crowding, and electrostatic forces of the electric double layer in the electrode materials having simple cubic (SC), body-centered cubic (BCC), and face-centered cubic (FCC) morphologies. The study manifests the effect of thickness of electrodes, electrode's particle size, and porosity on electric double-layer specific capacitance (EDLC). Electrochemical interference and the specific capacitance depend on the packing factor. The larger particle size decreases the specific capacitance, but porosity increases due to more surface area. Due to symmetry, SC, BCC, and FCC morphologies have 1, 3, and 5 spheres in a unit cell. The number of unit cells is varied from 1 to 100 in model 1 to analyze the effect of electrode thickness. Model 2 has three unit cells to understand the effect of porosity, and only pore lengths are varied. The critical thickness of the electrodes is the integer multiples of 1.71µm in all the morphologies. The Stern layer-specific capacitance is 167.6µF cm-2in all cases. The EDLC in BCC is around 5.6-7.6µF cm-2in the steady state that is intermediate between SC and FCC morphologies. The more dense packing of carbon particles in a unit cell increases the energy storage capabilities of electrodes. The average electrode permittivity slightly decreases due to the combined effect of the high electric field, status of polarization, and electrode particle size. The least optical transmission of electrodes is 98.35%.

Radically truncated MeCP2 rescues Rett syndrome-like neurological defects.

Heterozygous mutations in the X-linked MECP2 gene cause the neurological disorder Rett syndrome. The methyl-CpG-binding protein 2 (MeCP2) protein is an epigenetic reader whose binding to chromatin primarily depends on 5-methylcytosine. Functionally, MeCP2 has been implicated in several cellular processes on the basis of its reported interaction with more than 40 binding partners, including transcriptional co-repressors (for example, the NCoR/SMRT complex), transcriptional activators, RNA, chromatin remodellers, microRNA-processing proteins and splicing factors. Accordingly, MeCP2 has been cast as a multi-functional hub that integrates diverse processes that are essential in mature neurons. At odds with the concept of broad functionality, missense mutations that cause Rett syndrome are concentrated in two discrete clusters coinciding with interaction sites for partner macromolecules: the methyl-CpG binding domain and the NCoR/SMRT interaction domain. Here we test the hypothesis that the single dominant function of MeCP2 is to physically connect DNA with the NCoR/SMRT complex, by removing almost all amino-acid sequences except the methyl-CpG binding and NCoR/SMRT interaction domains. We find that mice expressing truncated MeCP2 lacking both the N- and C-terminal regions (approximately half of the native protein) are phenotypically near-normal; and those expressing a minimal MeCP2 additionally lacking a central domain survive for over one year with only mild symptoms. This minimal protein is able to prevent or reverse neurological symptoms when introduced into MeCP2-deficient mice by genetic activation or virus-mediated delivery to the brain. Thus, despite evolutionary conservation of the entire MeCP2 protein sequence, the DNA and co-repressor binding domains alone are sufficient to avoid Rett syndrome-like defects and may therefore have therapeutic utility.

Dengue virus 2 capsid protein chaperones the strand displacement of 5'-3' cyclization sequences.

By virtue of its chaperone activity, the capsid protein of dengue virus strain 2 (DENV2C) promotes nucleic acid structural rearrangements. However, the role of DENV2C during the interaction of RNA elements involved in stabilizing the 5'-3' panhandle structure of DENV RNA is still unclear. Therefore, we determined how DENV2C affects structural functionality of the capsid-coding region hairpin element (cHP) during annealing and strand displacement of the 9-nt cyclization sequence (5CS) and its complementary 3CS. cHP has two distinct functions: a role in translation start codon selection and a role in RNA synthesis. Our results showed that cHP impedes annealing between 5CS and 3CS. Although DENV2C does not modulate structural functionality of cHP, it accelerates annealing and specifically promotes strand displacement of 3CS during 5'-3' panhandle formation. Furthermore, DENV2C exerts its chaperone activity by favouring one of the active conformations of cHP. Based on our results, we propose mechanisms for annealing and strand displacement involving cHP. Thus, our results provide mechanistic insights into how DENV2C regulates RNA synthesis by modulating essential RNA elements in the capsid-coding region, that in turn allow for DENV replication.

Prospective observational study of clinical outcomes in using posterior interosseous free flap for finger defects.

Finger injuries are common in hand and plastic surgery practice. There are various options for reconstructing finger defects. Moderate sized skin defects of the fingers which need flaps are commonly covered using various abdominal flaps. These conventional workhorse flaps are thick, need two-staged procedures and require the hand to be kept in a cumbersome position. The radial artery or the ulnar artery flap need sacrifice a major vessel. To address the above, we have used the posterior interosseous artery free flap to cover finger defects. This was a prospective observational clinical study done on 15 patients admitted to a tertiary level hospital from July 2017 to July 2021. These patients had accidental industrial injuries with a loss of soft tissue on the fingers. There were finger fractures in 6 cases. These patients underwent posterior interosseous artery free flap cover. The flap size ranged from 6 × 3 cm to 10 × 4 cm. We had to cover the donor defects with skin graft in all our cases. Fourteen out of 15 flaps survived, with loss of one flap due to venous congestion. The mean two-point discrimination was 7.8 mm, with a total active motion percentage of more than 70% in 11 out of 15 cases. The posterior interosseous artery flap is a thin and pliable one stage flap, and may not need further flap thinning either, thereby establishing itself as a single stage procedure and moreover not requiring sacrifice a major vessel.

Assessment of spectral properties of positive dysphotopsia or glare caused by LED sources for different types of intraocular lenses.

Light emitting diodes (LEDs) have become a major source of lighting conditions. The increased prevalence of LED light sources introduces new concerns for the spectral effects of positive dysphotopsia (PD) or glare type photic phenomena for pseudo-phakic patients with intraocular lenses (IOLs). A significant amount of work has been published in the area of spectral discomfort and sensitivity of LEDs as well as automotive lighting. The wavelength dependence or spectral properties of PD due to LEDs for IOLs has not been reported. This study, to our knowledge, is the first one to assess the glare characteristics of four commercially available IOL models with different material types and design features using an optical bench and non-sequential ray trace simulations with LEDs of different wavelengths. A novel approach of representing the reflected and transmitted IOL glare utilizing Fresnel coefficients is found to be in close agreement with the measurements.

Microhydration of Phenyl Formate: Gas-Phase Laser Spectroscopy, Microwave Spectroscopy, and Quantum Chemistry Calculations.

Herein, we have investigated the structure of phenyl formate⋅⋅⋅water (PhOF⋅⋅⋅H2 O) dimer and various non-covalent interactions present there using gas-phase laser spectroscopy and microwave spectroscopy combined with quantum chemistry calculations. Two conformers of PhOF⋅⋅⋅H2 O (C1 and T1), built on the two cis/trans conformers of the bare molecule, have been observed in the experiment. In cis-PhOF, there is an nCO → π A r * ${{{\rm \pi }}_{{\rm A}{\rm r}}^{{\rm {^\ast}}}}$ interaction between the lone-pair orbital of the carbonyl oxygen atom and the π* orbital of the phenyl ring, which persists in the monohydrated C1 conformer of PhOF⋅⋅⋅H2 O according to the NBO and NCI analyses. On the other hand, this interaction is absent in the trans-PhOF conformer as the C=O group is away from the phenyl ring. The C1 conformer is primarily stabilized by an interplay between O-H⋅⋅⋅O=C hydrogen bond and O-H⋅⋅⋅π interactions, while the stability of the T1 conformer is primarily governed by the O-H⋅⋅⋅O=C hydrogen bond. The most important finding of the present work is that the conformational preference of the PhOF monomer is retained in its monohydrated complex.

Simulation Study of Electric Double-Layer Capacitance of Ordered Carbon Electrodes.

Supercapacitors are electrochemical energy storage devices having high capacitance, high power density, long cycle life, low cost, easy maintenance, and negligible environmental pollution. The formation of an electric double layer at the electrode-electrolyte interface is mostly responsible for supercapacitors' energy storage. The simulation study of equilibrium electric double-layer capacitance (EDLC) in 3D arranged mesoporous carbon electrodes with a simple cubic morphology and interdigitated electrodes has been done. Continuum theory has been utilized to study the underlying processes involved in EDLC. Interfacial polarization and ion crowding depend on the electrode's critical thickness. Porosity increases the capacitance due to the increase in the electrode surface area. The diffuse-layer specific capacitance of ordered mesoporous carbon electrodes in a (C2H5)4NBF4/propylene carbonate organic electrolyte is in the range of 3.2-13.3 µF cm-2, varying according to the electrode thickness. The Stern-layer specific capacitance is 167.6 µF cm-2, and total equilibrium EDLC is in the range of 3.1-12.3 µF cm-2. The effect of the electric field at the electrode-electrolyte interface on reducing electrolyte permittivity has also been discussed. The EDLC of carbonized interdigitated electrodes is analyzed in a 6 M KOH electrolyte. The diffuse-layer specific capacitance ranges from 118.7 to 352.0 µF cm-2 depending on the width of the interdigitated electrodes. The Stern-layer specific capacitance is 91.2 µF cm-2, and the total EDLC value is 51.6-72.4 µF cm-2. The modeling and simulation approach can be applied to different mesoporous electrodes by varying the supercapacitor component's parameters and geometry.

Shared intent in third-party donation will underpin the success of new surrogacy laws.

The demands for surrogacy treatments continue to grow worldwide. However the legal guidance for non-commercial surrogacy treatments remains inadequate, and this commentary argues how the forthcoming guidance on surrogacy from the UK Law Commissions would benefit from a bold decision based on previous experience derived from similar developments in three other areas of assisted conception.