Myeloid-derived suppressor cells in the tumor microenvironment reduce uncoupling protein 1 expression to boost immunosuppressive activity.

Uncoupling protein 1 (UCP1) is located at the inner membrane of mitochondria and mediates nonshivering thermogenesis. Its abnormal expression is associated with metabolic diseases, cancer, and acute kidney injury. Myeloid-derived suppressor cells (MDSCs) with immunosuppressive activity accumulate in the tumor microenvironment (TME). Here, decreased UCP1 expression in MDSCs was observed in the peripheral blood of patients with colorectal cancer and transplanted mouse tumors. Aggravated tumor progression was observed in UCP1-knockout mice and conditional knockout mice (UCP1fl/fl-S100A8cre). The number of G-MDSCs and M-MDSCs increased in the transplanted tumor tissues from UCP1-deficient mice compared with those from wild-type mice. The tumor-promoting effect disappeared when the tumor-bearing mice were depleted of MDSCs by the α-DR5 administration. Adoptive transfer of tumor-derived MDSCs sharply promoted the tumor growth in vivo. Furthermore, these tumor-derived MDSCs enhanced the proliferation, reduced death, inhibited IFN-γ production of CD4+ and CD8+T cells, and induced Treg cells ex vivo. In conclusion, MDSCs in the TME alter the metabolic pattern by decreasing UCP1 expression to enhance immunosuppressive activity for tumor escape.

Expression and function of myelin expression factor 2 in hepatocellular carcinoma.

INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most common malignant tumours in the world and has a high mortality rate. However, the pathogenesis of HCC remains unclear. This study aimed to investigate the potential biomarkers of HCC. METHODS: ONCOMINE, HCCDB and THE HUMAN PROTEIN ATLAS were used to identify myelin expression factor 2 (MYEF2) as a potential biomarker for HCC. The Cancer Genome Atlas database was used to further validate and analyse the value of MYEF2. Kaplan-Meier Plotter was used for the prognostic analysis. The COX regression model and Kaplan-Meier method were used to investigate the clinical value of MYEF2 in the prognosis of HCC by reviewing the survival status of patients. Fluorescent quantitative polymerase chain reaction (qPCR) and immunohistochemistry were used to detect the expressions of the MYEF2 mRNA and protein in HCC tissues and cell lines. qPCR and Western blotting were used to validate the efficiency of MYEF2 knockout and overexpression in HCC cells. The invasion and migration abilities regulated by MYEF2 were detected by performing transwell and wound healing assays. RESULTS: MYEF2 is significantly upregulated in HCC and is mainly located in the nucleus of HCC cells. MYEF2 expression is significantly associated with the tumour stage, histological grade and TNM stage. High MYEF2 expression is an independent prognostic factor for patients with HCC. Functionally, elevated MYEF2 facilitated cell migration and invasion in vitro. In contrast, decreased MYEF2 inhibited cell migration and invasion. CONCLUSIONS: MYEF2 may be a novel biomarker with potential diagnosis and prognosis values and as a potential therapeutic target for HCC.

Standardized Iterative Genome Editing Method for Escherichia coli Based on CRISPR-Cas9.

The introduction of complex biosynthetic pathways into the hosts' chromosomes is gaining attention with the development of synthetic biology. While CRISPR-Cas9 has been widely employed for gene knock-in, the process of multigene insertion remains cumbersome due to laborious and empirical gene cloning procedures. To address this, we devised a standardized iterative genome editing system for Escherichia coli, harnessing the power of CRISPR-Cas9 and MetClo assembly. This comprehensive toolkit comprises two fundamental elements based on the Golden Gate standard for modular assembly of sgRNA or CRISPR arrays and donor DNAs. We achieved a gene insertion efficiency of up to 100%, targeting a single locus. Expression of tracrRNA using a strong promoter enhances multiplex genomic insertion efficiency to 7.3%, compared with 0.76% when a native promoter is used. To demonstrate the robust capabilities of this genome editing toolbox, we successfully integrated 5-10 genes from the coenzyme B12 biosynthetic pathway ranging from 5.3 to 8 Kb in length into the chromosome of E. coli chassis cells, resulting in 14 antibiotic-free, plasmid-free producers. Following an extensive screening process involving genes from diverse sources, cistronic design modifications, and chromosome repositioning, we obtained a recombinant strain yielding 1.49 mg L-1 coenzyme B12, the highest known titer achieved by using E. coli as the producer. Illuminating its user-friendliness, this genome editing system is an exceedingly versatile tool for expediently integrating complex biosynthetic pathway genes into hosts' genomes, thus facilitating pathway optimization for chemical production.

Multivariate modular metabolic engineering and medium optimization for vitamin B12 production by Escherichia coli.

Vitamin B12 is a complex compound synthesized by microorganisms. The industrial production of vitamin B12 relies on specific microbial fermentation processes. E. coli has been utilized as a host for the de novo biosynthesis of vitamin B12, incorporating approximately 30 heterologous genes. However, a metabolic imbalance in the intricate pathway significantly limits vitamin B12 production. In this study, we employed multivariate modular metabolic engineering to enhance vitamin B12 production in E. coli by manipulating two modules comprising a total of 10 genes within the vitamin B12 biosynthetic pathway. These two modules were integrated into the chromosome of a chassis cell, regulated by T7, J23119, and J23106 promoters to achieve combinatorial pathway optimization. The highest vitamin B12 titer was attained by engineering the two modules controlled by J23119 and T7 promoters. The inclusion of yeast powder to the fermentation medium increased the vitamin B12 titer to 1.52 mg/L. This enhancement was attributed to the effect of yeast powder on elevating the oxygen transfer rate and augmenting the strain's isopropyl-ß-d-1-thiogalactopyranoside (IPTG) tolerance. Ultimately, vitamin B12 titer of 2.89 mg/L was achieved through scaled-up fermentation in a 5-liter fermenter. The strategies reported herein will expedite the development of industry-scale vitamin B12 production utilizing E. coli.

Up-regulation of NFATc4 involves in neuronal apoptosis following intracerebral hemorrhage.

Nuclear factor of activated T-cells, cytoplasmic 4 (NFATc4), a transcriptional factor, is involved in the control about the flow of genetic information and the modulation of diverse cellular activities. Accumulating evidence has demonstrated that NFATc4 exerted a pro-apoptotic effect in multiple diseases. Here, we explored the NFATc4's roles during the pathophysiological processes of intracerebral hemorrhage (ICH). An ICH rat model was built and evaluated according to behavioral testing. Using Western blot, immunohistochemistry, and immunofluorescence, significant up-regulation of NFATc4 was found in neurons in brain areas surrounding the hematoma following ICH. Increasing NFATc4 expression was found to be accompanied by the up-regulation of Fas ligand (FasL), active caspase-8, and active caspase-3, respectively. Besides, NFATc4 co-localized with active caspase-3 in neurons, indicating its role in neuronal apoptosis. Our in vitro study, using NFATc4 RNA interference in PC12 cells, further confirmed that NFATc4 might exert its pro-apoptotic function in neuronal apoptosis through extrinsic pathway. Thus, NFATc4 may play a role in promoting the brain secondary damage following ICH.

Effect of the acceptor on the performance of dye-sensitized solar cells.

Three new phenothiazine dyes were designed and synthesized, utilizing different acceptor groups. Upon application to TiO2-based solar cells, the effects of different acceptors on the photophysical and electrochemical properties of the dyes and the solar cell performance are detailed. The introduction of a pyridinium unit or 5-carboxy-1-hexyl-2,3,3-trimethyl-indolium unit into the molecular frame as the acceptor instead of cyano acrylic acid can effectively cause a red shift in the absorption spectra. Applied to DSSCs, the devices sensitized by CM502 with the pyridinium unit as the acceptor show the highest efficiency of 7.3%. The devices fabricated with dye CM501 with cyano acrylic acid as the acceptor exhibited the highest Voc while for the devices sensitized by the dye CM503 with 5-carboxy-1-hexyl-2,3,3-trimethyl-3H-indolium unit as the acceptor, the Voc value was the lowest, at 494 mV. The addition of TBP in the electrolyte can improve the performance of DSSCs fabricated using CM501 and CM502, with the Voc value greatly improved but the Jsc value slightly decreased. However, with the addition of TBP in the electrolyte, the efficiency of the cells sensitized by CM503 dropped significantly (from 4.9% to 1.0% when 0.1 M TBP was added).

Dye-sensitized solar cells based on hydroquinone/benzoquinone as bio-inspired redox couple with different counter electrodes.

In the present study, tetramethylammonium hydroquinone (HQ)/benzoquinone (BQ) were developed for use as a redox couple, with poly(3,4-ethylenedioxythiophene) (PEDOT) and multiwalled carbon nanotubes (MWNT) being proposed for use as counter electrode (CE) catalysts in dye-sensitized solar cells (DSSCs). Both metal-complex N719 and metal-free organic dye CM309 were employed to fabricate devices. For the devices sensitized by N719, when using PEDOT and MWNT CEs, power conversion efficiencies (PCE) of 5.2 and 4.9% were obtained, respectively, which were much higher than that of the device using the traditional Pt CE (4.7%) when HQ/BQ electrolyte was employed. However, with the HQ/BQ redox shuttle, the efficiency of the devices sensitized by N719 is much lower than that of the devices when the traditional I(-)/I3(-) based electrolyte and Pt CE were employed (7.9%). While for the CM309 sensitized solar cells, when the HQ/BQ redox shuttle was employed, PEDOT and MWNT performed much better than Pt, the DSSC using the PEDOT CE showed an efficiency of 6.2%, which was close to that of the DSSC using the traditional I(-)/I3(-) electrolyte and Pt CE (6.3%).

DLAT is a promising prognostic marker and therapeutic target for hepatocellular carcinoma: a comprehensive study based on public databases.

Cuproptosis is a new mechanism of cell death that differs from previously identified regulatory cell death mechanisms. Cuproptosis induction holds promise as a new tumour treatment. Therefore, we investigated the value of cuproptosis-related genes in the management of hepatocellular carcinoma (HCC). The cuproptosis-related gene Dihydrolipoamide S-Acetyltransferase (DLAT) were significantly upregulated in liver cancer tissues. High levels of DLAT were an independent prognostic factor for shorter overallsurvival (OS) time. DLAT and its related genes were mainly involved in cell metabolism, tumor progression and immune regulation. DLAT was significantly associated with the level of immune cell infiltration and immune checkpoints in HCC. HCC with high DLAT expression was predicted to be more sensitive to sorafenib treatment. The risk prognostic signature established based on DLAT and its related genes had a good prognostic value. The cuproptosis-related gene DLAT is a promising independent prognostic marker and therapeutic target in HCC. The new prognostic signature can effectively predict the prognosis of HCC patients.

Dye-sensitized solar cells based on a donor-acceptor system with a pyridine cation as an electron-withdrawing anchoring group.

New hemicyanine dyes (CM101, CM102, CM103, and CM104) in which tetrahydroquinoline derivatives are used as electron donors and N-(carboxymethyl)-pyridinium is used as an electron acceptor and anchoring group were designed and synthesized for dye-sensitized solar cells (DSSCs). Compared with corresponding dyes that have cyanoacetic acid as the acceptor, N-(carboxymethyl)-pyridinium has a stronger electron-withdrawing ability, which causes the absorption maximum of dyes to be redshifted. The photovoltaic performance of the DSSCs based on dyes CM101-CM104 markedly depends on the molecular structures of the dyes in terms of the n-hexyl chains and methoxyl. The device sensitized by dye CM104 achieved the best conversion efficiency of 7.0% (J(sc) = 13.4 mA cm(-2), V(oc) = 704 mV, FF = 74.8%) under AM 1.5 irradiation (100 mW cm(-2)). In contrast, the device sensitized by reference dye CMR104 with the same donor but the cyanoacetic acid as the acceptor gave an efficiency of 3.4% (J(sc) =6.2 mA cm(-2), V(oc) = 730 mV, FF = 74.8%). Under the same conditions, the cell fabricated with N719 sensitized porous TiO(2) exhibited an efficiency of 7.9% (J(sc) = 15.4 mA cm(-2) , V(oc) = 723 mV, FF = 72.3%). The dyes CM101-CM104 show a broader spectral response compared with the reference dyes CMR101-CMR104 and have high IPCE exceeding 90% from 450 to 580 nm. Considering the reflection of sunlight, the photoelectric conversion efficiency could be almost 100% during this region.

[MTCARI: A kind of vegetation index monitoring vegetation leaf chlorophyll content based on hyperspectral remote sensing].

The chlorophyll content of plant has relative correlation with photosynthetic capacity and growth levels of plant. It affects the plant canopy spectra, so the authors can use hyperspectral remote sensing to monitor chlorophyll content. By analyzing existing mature vegetation index model, the present research pointed out that the TCARI model has deficiencies, and then tried to improve the model. Then using the PROSPECT+SAIL model to simulate the canopy spectral under different levels of chlorophyll content and leaf area index (LAI), the related constant factor has been calculated. The research finally got modified transformed chlorophyll absorption ratio index (MTCARI). And then this research used optimized soil background adjust index (OSAVI) to improve the model. Using the measured data for test and verification, the model has good reliability.

Efficient dye-sensitized solar cells based on hydroquinone/benzoquinone as a bioinspired redox couple.

A hybrid electrolyte involving tetramethylammonium (TMA) hydroquinone/benzoquinone redox couple is formulated. This electrolyte is more transparent than the traditional I(-)/I(3)(-) electrolyte and has negligible absorption in the visible region. Dye-sensitized solar cells using the hybrid electrolyte show higher light-to-electricity conversion efficiency. FTO=fluorine-doped tin oxide.

Novel BiOBr by compositing low-cost biochar for efficient ciprofloxacin removal: the synergy of adsorption and photocatalysis on the degradation kinetics and mechanism insight.

C/BiOBr composite materials were synthesized via a simple one-step solvothermal method, with C derived from biochar, which was prepared from the low-cost straw. The samples were characterized by SEM, XRD, XPS and PL. The 2% C/BiOBr composite material showed a noticeable adsorption and photocatalysis synergistic effect to remove CIP. The adsorption rate and degradation rate were 1.45 times and 1.8 times that of BiOBr. The adsorption kinetics and isotherms of CIP on C/BiOBr were analyzed with the pseudo-second-order kinetic and Langmuir models. The degradation efficiency was 96.8% after 60 min of irradiation. High stability and degradability were still maintained after four cycles. The Bi-O-C bond accelerated electron transition and inhibited the rapid photogenerated electron pair recombination. In the degradation process of CIP, ˙O2 - and h+ played a significant role. Experiments proved that C/BiOBr is practical and feasible for the degradation of CIP under the synergistic effect of adsorption and photocatalysis.

Effect of different numbers of -CH2- units on the performance of isoquinolinium dyes.

Three new dyes have been synthesized to investigate the influence of the distance between the electron acceptor and TiO2 surface on the performance of dye-sensitized solar cells (DSSCs). In these dyes, the isoquinolinium acceptor, with a -(CH2)nCOOH anchoring group, and a functionalized triphenylamine donor are separated by an oligothiophene bridge. The physical and electrochemical properties of the dyes were investigated systematically. The results prove that different numbers of -CH2- units between the isoquinolinium acceptor and the carboxyl anchoring group have a less pronounced effect on the physical and electrochemical properties of these dyes. However, when applied in DSSCs, a sharp decrease in the short-circuit current (Jsc) was observed with increasing numbers of -CH2- units. For example, the device containing the organic dye bearing three -CH2- units produced the lowest Jsc of 7.94 mA·cm(-2). In contrast, the device containing the dye bearing only one -CH2- unit exhibited the highest Jsc of 13.88 mA·cm(-2). The higher photocurrent obtained with the device incorporating the dye with one -CH2- unit resulted in a higher power conversion efficiency of 6.8%.

Efficient organic sensitizers with pyridine-N-oxide as an anchor group for dye-sensitized solar cells.

Five organic dyes with pyridine-N-oxide as the anchor group and electron acceptor have been synthesized and applied in dye-sensitized solar cells (DSSCs). Benzothiadiazole was introduced in the conjugation system to increase the electron withdrawing properties, FTIR spectra showed that the coordination was between the pyridine-N-oxide and the Brønsted acid site on the TiO2 surface. The relationship between different dye structures and the performance of the DSSCs was investigated systematically. The location of the thiophene unit was studied, and the direct linkage of benzothiadiazole with pyridine-N-oxide was beneficial to broaden the absorption. The donor-acceptor-acceptor-configured dye WL307, which has 2-ethylhexyloxy chains in the donor part, showed the best efficiency of 6.08% under 100 mW cm(-2) light illumination. The dye series showed a fairly good stability during the one month test period.

Structure engineering of hole-conductor free perovskite-based solar cells with low-temperature-processed commercial carbon paste as cathode.

Low-temperature-processed (100 °C) carbon paste was developed as counter electrode material in hole-conductor free perovskite/TiO2 heterojunction solar cells to substitute noble metallic materials. Under optimized conditions, an impressive PCE value of 8.31% has been achieved with this carbon counter electrode fabricated by doctor-blading technique. Electrochemical impedance spectroscopy demonstrates good charge transport characteristics of low-temperature-processed carbon counter electrode. Moreover, this carbon counter electrode-based perovskite solar cell exhibits good stability over 800 h.

Molecular design and performance of hydroxylpyridium sensitizers for dye-sensitized solar cells.

Four hydroxylpyridium organic dyes were synthesized and applied in dye-sensitized solar cells (DSSCs). Hydroxylpyridium was introduced as an electron acceptor in donor-π-conjugated bridge-acceptor (D-π-A) system. The traditional anchoring groups, such as the carboxyl group, were replaced by hydroxyl group. It was found that the existence of the hydroxylpyridium exhibits a large effect on the absorption spectra of dyes JH401-JH404. For JH series of dyes, hexylthiophene was employed as the π-conjugated bridge, and triphenylamine, phenothiazine, and their derivatives were used as the electron donor. The performances of the dyes with different structure were investigated by photophysical, photovoltaic, and electrochemical methods. When applied in the DSSCs, the sensitizer JH401 yields the best efficiency, 2.6% (Jsc = 6.35 mA/cm(2), Voc = 605 mV, FF = 67.6%) under 100 mW/cm(2) light illumination. Its maximum incident photon-to-current conversion efficiency (IPCE) is 80% at 440 nm light wavelength, which is the highest IPCE value achieved with hydroxyl group adsorbent organic dyes so far.

Efficient organic dye-sensitized solar cells: molecular engineering of donor-acceptor-acceptor cationic dyes.

Three metal-free donor-acceptor-acceptor sensitizers with ionized pyridine and a reference dye were synthesized, and a detailed investigation of the relationship between the dye structure and the photophysical and photoelectrochemical properties and the performance of dye-sensitized solar cells (DSSCs) is described. The ionization of pyridine results in a red shift of the absorption spectrum in comparison to that of the reference dye. This is mainly attributable to the ionization of pyridine increasing the electron-withdrawing ability of the total acceptor part. Incorporation of the strong electron-withdrawing units of pyridinium and cyano acrylic acid gives rise to optimized energy levels, resulting in a large response range of wavelengths. When attached to TiO2 film, the conduction band of TiO2 is negatively shifted to a different extent depending on the dye. This is attributed to the electron recombination rate between the TiO2 film and the electrolyte being efficiently suppressed by the introduction of long alkyl chains and thiophene units. DSSCs assembled using these dyes show efficiencies as high as 8.8 %.

Efficient panchromatic organic sensitizers with dihydrothiazole derivative as π-bridge for dye-sensitized solar cells.

Novel organic dyes CC201 and CC202 with dihydrothiazole derivative as π-bridge have been synthesizedand applied in the DSSCs. With the synergy electron-withdrawing of dihydrothiazole and cyanoacrylic acid, these two novel dyes CC201 and CC202 show excellent response in the region of 500-800 nm. An efficiency as high as 6.1% was obtained for the device fabricated by sensitizer CC202 together with cobalt electrolyte under standard light illumination (AM 1.5G, 100 mW cm(-2)). These two novel D-π-A panchromatic organic dyes gave relatively high efficiencies except common reported squaraine dyes.