Efficacy and safety of different polymyxin-containing regimens for the treatment of pneumonia caused by multidrug-resistant gram-negative bacteria: a systematic review and network meta-analysis.

BACKGROUND: The optimal administration of polymyxins for treating multidrug-resistant gram-negative bacterial (MDR-GNB) pneumonia remains unclear. This study aimed to systematically assess the efficacy and safety of three polymyxin-containing regimens by conducting a comprehensive network meta-analysis. METHODS: We comprehensively searched nine databases. Overall mortality was the primary outcome, whereas the secondary outcomes encompassed microbial eradication rate, clinical success, acute kidney injury, and incidence of bronchospasm. Extracted study data were analyzed by pairwise and network meta-analyses. Version 2 of the Cochrane risk-of-bias tool and the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) assessment tool were used to assess the risk of bias in randomized trials and cohort studies, respectively. RESULTS: This study included 19 observational studies and 3 randomized controlled trials (RCTs), encompassing 3318 patients. Six studies with high risk of bias were excluded from the primary analysis. In the pairwise meta-analysis, compared to the intravenous (IV) polymyxin-containing regimen, the intravenous plus inhaled (IV + IH) polymyxin-containing regimen showed a significant decrease in overall mortality, while no statistically significant difference was found in the inhaled (IH) polymyxin-containing regimen. The network meta-analysis indicated that the IV + IH polymyxin-containing regimen had significantly lower overall mortality (OR 0.67; 95% confidence interval [CI] 0.50-0.88), higher clinical success rate (OR 1.90; 95% CI 1.20-3.00), better microbial eradication rate (OR 2.70; 95% CI 1.90-3.90) than the IV polymyxin-containing regimen, and significantly better microbial eradication rate when compared with the IH polymyxin-containing regimen (OR 2.30; 95% CI 1.30-4.20). Furthermore, compared with IV + IH and IV polymyxin-containing regimens, the IH polymyxin-containing regimen showed a significant reduction in acute kidney injury. CONCLUSIONS: Our study indicates that among the three administration regimens, the IV + IH polymyxin-containing regimen may be the most effective for treating MDR-GNB pneumonia, with a significantly lower overall mortality compared to the IV regimen and a considerably higher microbial eradication rate compared to the IH regimen. The IH regimen may be considered superior to the IV regimen due to its substantially lower incidence of acute kidney injury, even though the reduction in overall mortality was not significant.

Fully Optical Control of Polarization Current Direction in a Cyanide-Bridged Trinuclear Complex.

As a remote and non-contact stimulus, light offers the potential for manipulating the polarization of ferroelectric materials without physical contact. However, in current research, the non-contact write-read (erase) process lacks direct observation through the stable current as output signal. To address this limitation, we investigated the photoinduced polarization switching capabilities of the cyanide-bridged compound [Fe2Co] using visible light, leading to the achievement of rewritable polarization. By subjecting [Fe2Co] crystals to alternating irradiation with 785 nm and 532 nm light, the polarization changes exhibited a distinct square wave pattern, confirming the reliability of the writing and erasing processes. Initialization involved exposing specific crystal units to 532 nm light for storing "1" or "0" information, while reading was accomplished by scanning the units with 785 nm light, resulting in brief current pulses for "1" states and no current signal for "0" states. This research unveils new possibilities for optical storage systems, paving the way for efficient and rewritable data storage and retrieval technologies, such as the next-generation memories.

Exchange Bias Induced by the Spin-Glass-Like State in a Te-Rich FeGeTe van der Waals Ferromagnet.

We have experimentally investigated the mechanism of the exchange bias in 2D van der Waals (vdW) ferromagnets by means of the anomalous Hall effect (AHE) together with the dynamical magnetization property. The temperature dependence of the AC susceptibility with its frequency response indicates a glassy transition of the magnetic property for the Te-rich FeGeTe vdW ferromagnet. We also found that the irreversible temperature dependence in the anomalous Hall voltage follows the de Almeida-Thouless line. Moreover, the freezing temperature of the spin-glass-like phase is found to correlate with the disappearance temperature of the exchange bias. These important signatures suggest that the emergence of magnetic exchange bias in the 2D van der Waals ferromagnets is induced by the presence of the spin-glass-like state in FeGeTe. The unprecedented insights gained from these findings shed light on the underlying principles governing exchange bias in vdW ferromagnets, contributing to the advancement of our understanding.

Integrating spin-dependent emission and dielectric switching in FeII catenated metal-organic frameworks.

Mechanically interlocked molecules (MIMs) including famous catenanes show switchable physical properties and attract continuous research interest due to their potential application in molecular devices. The advantages of using spin crossover (SCO) materials here are enormous, allowing for control through diverse stimuli and highly specific functions, and enabling the transfer of the internal dynamics of MIMs from solution to solid state, leading to macroscopic applications. Herein, we report the efficient self-assembly of catenated metal-organic frameworks (termed catena-MOFs) induced by stacking interactions, through the combination of rationally selected flexible and conjugated naphthalene diimide-based bis-pyridyl ligand (BPND), [MI(CN)2]- (M = Ag or Au) and Fe2+ in a one-step strategy. The obtained bimetallic Hofmann-type SCO-MOFs [FeII(BPND){Ag(CN)2}2]·3CHCl3 (1Ag) and [FeII(BPND{Au(CN)2}2]·2CHCl3·2H2O (1Au) possess a unique three-dimensional (3D) catena-MOF constructed from the polycatenation of two-dimensional (2D) layers with hxl topology. Both complexes undergo thermal- and light-induced SCO. Significantly, abnormal increases in the maximum emission intensity and dielectric constant can be detected simultaneously with the switching of spin states. This research opens up SCO-actuated bistable MIMs that afford dual functionality of coupled fluorescence emission and dielectricity.

Phospholipid-Anchored Ligand Conjugation on Extracellular Vesicles for Enhanced Cancer Targeting.

Extracellular vesicles (EVs) are recognized as potential candidates for next-generation drug delivery systems. However, the inherent cancer-targeting efficiency is unsatisfactory, necessitating surface modification to attach cell-binding ligands. By utilizing phospholipase D from Streptomyces in combination with maleimide-containing primary alcohol, the authors successfully anchored ligands onto milk-derived EVs (mEVs), overcoming the issues of ligand leakage or functional alteration seen in traditional methods. Quantitative nano-flow cytometry demonstrated that over 90% of mEVs are effectively modified with hundreds to thousands of ligands. The resulting mEV formulations exhibited remarkable long-term stability in conjugation proportion, ligand number, size distribution, and particle concentration, even after months of storage. It is further shown that conjugating transferrin onto mEVs significantly enhanced cellular uptake and induced pronounced cytotoxic effects when loaded with paclitaxel. Overall, this study presents a highly efficient, stable, cost-effective, and scalable ligand conjugation approach, offering a promising strategy for targeted drug delivery of EVs.

Polar Crystals Using Molecular Chirality: Pseudosymmetric Crystallization toward Polarization Switching Materials.

Polar compounds with switchable polarization properties are applicable in various devices such as ferroelectric memory and pyroelectric sensors. However, a strategy to prepare polar compounds has not been established. We report a rational synthesis of a polar CoGa crystal using chiral cth ligands (SS-cth and RR-cth, cth = 5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane). Both the original homo metal Co crystal and Ga crystal exhibit a centrosymmetric isostructure, where the dipole moment of metal complexes with the SS-cth ligand and those with the RR-cth ligand are canceled out. To obtain a polar compound, the Co valence tautomeric complex with SS-cth in the homo metal Co crystal is replaced with the Ga complex with SS-cth by mixing Co valence tautomeric complexes with RR-cth and Ga complexes with SS-cth. The CoGa crystal exhibits polarization switching between the pseudononpolar state at a low temperature and the polar state at a high temperature because only Co complexes exhibit changes in electric dipole moment due to metal-to-ligand charge transfer. Following the same strategy, the polarization-switchable CoZn complex was synthesized. The CoZn crystal exhibits polarization switching between the polar state at a low temperature and the pseudononpolar state at a high temperature, which is the opposite temperature dependence to that of the CoGa crystal. These results revealed that the polar crystal can be synthesized by design, using a chiral ligand. Moreover, our method allows for the control of temperature-dependent polarization changes, which contrasts with typical ferroelectric compounds, in which the polar ferroelectric phase typically occurs at low temperatures.

Development of an FeII Complex Exhibiting Intermolecular Proton Shifting Coupled Spin Transition.

In this study, we investigated reversible intermolecular proton shifting (IPS) coupled with spin transition (ST) in a novel FeII complex. The host FeII complex and the guest carboxylic acid anion were connected by intermolecular hydrogen bonds (IHBs). We extended the intramolecular proton transfer coupled ST phenomenon to the intermolecular system. The dynamic phenomenon was confirmed by variable-temperature single-crystal X-ray diffraction, neutron crystallography, and infrared spectroscopy. The mechanism of IPS was further validated using density functional theory calculations. The discovery of IPS-coupled ST in crystalline molecular materials provides good insights into fundamental processes and promotes the design of novel multifunctional materials with tunable properties for various applications, such as optoelectronics, information storage, and molecular devices.

[Nonlinear Variations in PM2. 5 Concentration in the Three Major Urban Agglomerations in China].

ITA and Beast methods were used to quantitatively analyze the nonlinear process of a PM2.5 concentration time series based on the PM2.5 concentration data of the three major urban agglomerations in China. The results showed that： ① the degree of the PM2.5 pollution in the three major urban agglomerations had decreased， and the high-concentration areas had noticeably shrunk. The degree of spatial polarization of PM2.5 concentration was reduced， and the spatial difference was narrowed. The PM2.5 concentration in most areas showed downward trends， but the degree of change was not the same. Compared with the YRD and PRD， the concentration of PM2.5 in the BTH was still at a relatively high level. ② The concentration of PM2.5 in the three major urban agglomerations had seasonal variation characteristics that were high in winter and spring and low in summer and autumn. There were obvious differences in PM2.5 concentration between winter and summer， and the convergence of PM2.5 concentration in summer was greater than that in winter. Areas with high PM2.5 concentration also had obvious downward trends， but the downward trends of PM2.5 concentration in the PRD were not obvious compared with those in the YRD and BTH. ③ The PM2.5 concentration time series of the three major urban agglomerations all had significant downward trends： Beijing-Tianjin-Hebei （BTH） > the Yangtze River Delta （YRD） > the Pearl River Delta （PRD）. The PM2.5 concentration had the largest downward trends in winter. The higher the PM2.5 pollution level， the greater the downward trends. ④ The trend component of the PM2.5 concentration time series in the BTH had two change points， and there was one change point in the seasonal component. The trend and seasonal components of the PM2.5 concentration time series in the YRD had no change point. There was no change point in the seasonal component but one change point in the trend component of the PM2.5 concentration time series in the PRD. These results can provide scientific references for regional air pollution control.

Two-Dimensional Spin-Crossover Molecular Solid Solutions with Tunable Transition Temperatures across 90 K.

Spin-crossover (SCO) materials exhibit remarkable potential as bistable switches in molecular devices. However, the spin transition temperatures (Tc) of known compounds are unable to cover the entire ambient temperature spectrum, largely limiting their practical utility. This study reports an exemplary two-dimensional SCO solid solution system, [FeIII(H0.5LCl)2-2x(H0.5LF)2x]·H2O (H0.5LX = 5-X-2-hydroxybenzylidene-hydrazinecarbothioamide, X = F or Cl, x = 0 to 1), in which the adjacent layers are adhered via hydrogen bonding. Notably, the Tc of this system can be fine-tuned across 90 K (227-316 K) in a linear manner by modulating the fraction x of the LF ligand. Elevating x results in strengthened hydrogen bonding between adjacent layers, which leads to enhanced intermolecular interactions between adjacent SCO molecules. Single-crystal diffraction analysis and periodic density functional theory calculations revealed that such a special kind of alteration in interlayer interactions strengthens the FeIIIN2O2S2 ligand field and corresponding SCO energy barrier, consequently resulting in increased Tc. This work provides a new pathway for tuning the Tc of SCO materials through delicate manipulation of molecular interactions, which could expand the application of bistable molecular solids to a much wider temperature regime.

Photo-induced valence tautomerism and polarization switching in mononuclear cobalt complexes with an enantiopure chiral ligand.

Light-induced polarization switchable molecular materials have attracted attention for decades owing to their potential remote manipulation and ultrafast responsiveness. Here we report a valence tautomeric (VT) complex with an enantiopure chiral ligand. By a suitable choice of counter anions, a significant improvement in photoconversion has been demonstrated, leading to novel photo-responsive polarization switching materials.

Progress on the mechanism of natural products alleviating androgenetic alopecia.

Androgenetic alopecia (AGA) has become a widespread problem that leads to considerable impairment of the psyche and daily life. The currently approved medications for the treatment of AGA are associated with significant adverse effects, high costs, and prolonged treatment duration. Therefore, natural products are being considered as possible complementary or alternative treatments. This review aims to enhance comprehension of the mechanisms by which natural products treat AGA. To achieve this, pertinent studies were gathered and subjected to analysis. In addition, the therapeutic mechanisms associated with these natural products were organized and summarized. These include the direct modulation of signaling pathways such as the Wnt/ß-catenin pathway, the PI3K/AKT pathway, and the BMP pathway. Additionally, they exert effects on cytokine secretion, anti-inflammatory, and antioxidant capabilities, as well as apoptosis and autophagy. Furthermore, the review briefly discusses the relationship between signaling pathways and autophagy and apoptosis in the context of AGA, systematically presents the mechanisms of action of existing natural products, and analyzes the potential therapeutic targets based on the active components of these products. The aim is to provide a theoretical basis for the development of pharmaceuticals, nutraceuticals, or dietary supplements.

Electrically Detectable Photoinduced Polarization Switching in a Molecular Prussian Blue Analogue.

Light, a nondestructive and remotely controllable external stimulus, effectively triggers a variety of electron-transfer phenomena in metal complexes. One prime example includes using light in molecular cyanide-bridged [FeCo] bimetallic Prussian blue analogues, where it switches the system between the electron-transferred metastable state and the system's ground state. If this process is coupled to a ferroelectric-type phase transition, the generation and disappearance of macroscopic polarization, entirely under light control, become possible. In this research, we successfully executed a nonpolar-to-polar phase transition in a trinuclear cyanide-bridged [Fe2Co] complex crystal via directional electron transfer. Intriguingly, by exposing the crystal to the wavelength of light─785 nm─without any electric field─we can drive this ferroelectric phase transition to completely depolarize the crystal, during which a measurable electric current response can be detected. These discoveries signify an important step toward the realization of fully light-controlled ferroelectric memory devices.

[Scale Dependence Between PM2.5 and Meteorological Factors and Its Influencing Factors in "2+26" Cities].

Based on the PM2.5 concentration and meteorological data of "2+26" cities, the variations in PM2.5 time series were analyzed by the continuous wavelet transform(CWT) and discrete wavelet transform(DWT). Wavelet coherence(WTC) and multiple wavelet coherence(MWC) were used to quantify the response relationship between PM2.5 and single/multiple meteorological factors in the time-frequency domain. Partial wavelet coherence(PWC) was used to quantitatively evaluate the influence of atmospheric teleconnection factors on the response relationship. The results showed that:① the concentration of PM2.5 in the "2+26" cities had the spatial distribution characteristics of high in the middle area and low in the peripheral area. The PM2.5 mutation events were mainly concentrated before 2018 and mostly occurred in winter when the meteorological conditions were stable. The annual scale period of 256-512 d was relatively stable, and it was also the dominant period of the PM2.5 time series. ② The coherences between PM2.5 and meteorological factors depended on the time-frequency scale and variable combination. At all time-frequency scales, PM2.5 had strong coherences with relative humidity and temperature. At small and medium time-frequency scales, PM2.5 had strong coherences with wind speed. At large scales, PM2.5 had strong coherences with temperature. The combination of precipitation, temperature, and relative humidity could explain the variation in PM2.5 at all time-frequency scales. ③ At different time-frequency scales, the enhancement/weakening effects of atmospheric teleconnection factors on the response relationship were not the same. At all time-frequency scales, the El Niño-Southern Oscillation(ENSO) had a greater impact on the response relationship between PM2.5 and precipitation/temperature, and the Pacific decadal oscillation(PDO) had a greater impact on the response relationship between PM2.5 and relative humidity/wind speed. These results provide reference for regional air pollution control.

Discovery of Ingenane Diterpenoids from Euphorbia hylonoma as Antiadipogenic Agents.

Thirteen new Euphorbia diterpenoids, euphylonanes A-M (1-13), and eight known ones were isolated from the whole plants of Euphorbia hylonoma. Compounds 1 and 2 are two rearranged ingenanes bearing a rare 6/6/7/3-fused ring system. Compound 3 represents the first example of a 9,10-epoxy tigliane, while 4-21 are typical ingenanes varying with substituents. Structures were elucidated using a combination of spectroscopic, computational, and chemical methods. Most ingenanes exerted a significant antiadipogenic effect in 3T3-L1 adipocytes, among which 4 was the most active with an EC50 value of 0.60 ± 0.27 µM. Mechanistic study revealed that 4 inhibited the adipogenesis and lipogenesis in adipocytes via activation of the AMPK signaling pathway.

Regulation of species metabolism in synthetic community systems by environmental pH oscillations.

Constructing a synthetic community system helps scientist understand the complex interactions among species in a community and its environment. Herein, a two-species community is constructed with species A (artificial cells encapsulating pH-responsive molecules and sucrose) and species B (Saccharomyces cerevisiae), which causes the environment to exhibit pH oscillation behaviour due to the generation and dissipation of CO2. In addition, a three-species community is constructed with species A' (artificial cells containing sucrose and G6P), species B, and species C (artificial cells containing NAD+ and G6PDH). The solution pH oscillation regulates the periodical release of G6P from species A'; G6P then enters species C to promote the metabolic reaction that converts NAD+ to NADH. The location of species A' and B determines the metabolism behaviour in species C in the spatially coded three-species communities with CA'B, CBA', and A'CB patterns. The proposed synthetic community system provides a foundation to construct a more complicated microecosystem.

[Spatio-temporal Variations in PM2.5and Its Influencing Factors in the Yangtze River Delta Urban Agglomeration].

To coordinate the contradiction between economic development and environmental pollution and achieve the sustainable development of the economy and society, the spatio-temporal variations in PM2.5 were analyzed based on PM2.5 concentration and meteorological data of the Yangtze River Delta (YRD) urban agglomeration. Wavelet transform coherence (WTC), partial wavelet coherence (PWC), and multiple wavelet coherence (MWC) were used to analyze the multi-scale coupling oscillation between PM2.5 and meteorological factors in the time-frequency domain. The results showed that:① the concentration of PM2.5 in the YRD decreased from northwest to southeast, and the spatial range with high PM2.5 concentration decreased annually. The spatial distribution characteristics of the seasonal average PM2.5 concentration were similar to those of the annual average PM2.5 concentration. PM2.5 concentration exhibited the seasonal variation characteristics of high in winter, low in summer, and transitioning between spring and autumn. ② PM2.5 concentration decreased from 2015 to 2021, and the compliance rate increased. The difference in annual average PM2.5 concentration was decreased with dynamic convergence characteristics. The convergence of PM2.5 concentration in summer was greater than that in winter. During the whole study period, the daily average PM2.5 concentration showed a "U" distribution, and the proportion of days with excellent and good PM2.5 levels were 49.72% and 41.45%, respectively. ③ The wavelet coherence between PM2.5 and meteorological factors was different in different time-frequency domains. The main factors affecting PM2.5 were different in different time-frequency scales. At all time-frequency scales, WTC and PWC showed that wind speed and temperature were the best explanatory variables of PM2.5 variation, respectively. ④ The larger the time-frequency scale, the stronger the interaction of multi-factor combinations to explain PM2.5 variations. The synergistic effect of temperature and wind speed could better explain the variation in PM2.5. These results can provide reference for air pollution control in the YRD.

Control of electronic polarization via charge ordering and electron transfer: electronic ferroelectrics and electronic pyroelectrics.

Ferroelectric, pyroelectric, and piezoelectric compounds whose electric polarization properties can be controlled by external stimuli such as electric field, temperature, and pressure have various applications, including ferroelectric memory materials, sensors, and thermal energy-conversion devices. Numerous polarization switching compounds, particularly molecular ferroelectrics and pyroelectrics, have been developed. In these materials, the polarization switching usually proceeds via ion displacement and reorientation of polar molecules, which are responsible for the change in ionic polarization and orientational polarization, respectively. Recently, the development of electronic ferroelectrics, in which the mechanism of polarization change is charge ordering and electron transfer, has attracted great attention. In this article, representative examples of electronic ferroelectrics are summarized, including (TMTTF)2X (TMTTF = tetramethyl-tetrathiafulvalene, X = anion), α-(BEDT-TTF)2I3 (BEDT-TTF = bis(ethylenedithio)-tetrathiafulvalene), TTF-CA (TTF = tetrathiafulvalene, CA = p-chloranil), and [(n-C3H7)4N][FeIIIFeII(dto)3] (dto = 1,2-dithiooxalate = C2O2S2). Furthermore, polarization switching materials using directional electron transfer in nonferroelectrics, the so-called electronic pyroelectrics, such as [(Cr(SS-cth))(Co(RR-cth))(µ-dhbq)](PF6)3 (dhbq = deprotonated 2,5-dihydroxy-1,4-benzoquinone, cth = 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraaza-cyclotetradecane), are introduced. Future prospects are also discussed, particularly the development of new properties in polarization switching through the manipulation of electronic polarization in electronic ferroelectrics and electronic pyroelectrics by taking advantage of the inherent properties of electrons.

Call for special attention to the caregiver burden of patients with drug-resistant tuberculosis in low- and middle-income countries.

The tuberculosis (TB)-related caregiver burden (CB), and particularly the multidrug and extensively drug-resistant tuberculosis (M/XDR-TB)-related CB, is not rare in caregivers caring for TB patients, especially when a family member is the caregiver. However, the existing studies on this topic are insufficient. This study briefly summarized the risk factors for the imposition of a TB-related CB and reasons why caregivers for patients with M/XDR-TB are more susceptible to a CB. We propose that special measures should be implemented to alleviate the TB-related CB based on our clinical experience and insights from China. This may improve the situation of caregivers for TB patients and ultimately improve the quality of life of TB patients.

Quantifying the scale-dependent relationships of PM2.5 and O3 on meteorological factors and their influencing factors in the Beijing-Tianjin-Hebei region and surrounding areas.

To investigate the variations of PM2.5 and O3 and their synergistic effects with influencing factors at different time scales, we employed Bayesian estimator of abrupt seasonal and trend change to analyze the nonlinear variation process of PM2.5 and O3. Wavelet coherence and multiple wavelet coherence were utilized to quantify the coupling oscillation relationships of PM2.5 and O3 on single/multiple meteorological factors in the time-frequency domain. Furthermore, we combined this analysis with the partial wavelet coherence to quantitatively evaluate the influence of atmospheric teleconnection factors on the response relationships. The results obtained from this comprehensive analysis are as follows: (1) The seasonal component of PM2.5 exhibited a change point, which was most likely to occur in January 2017. The trend component showed a discontinuous decline and had a change point, which was most likely to appear in February 2017. The seasonal component of O3 did not exhibit a change point, while the trend component showed a discontinuous rise with two change points, which were most likely to occur in July 2018 and May 2017. (2) The phase and coherence relationships of PM2.5 and O3 on meteorological factors varied across different time scales. Stable phase relationships were observed on both small- and large-time scales, whereas no stable phase relationship was formed on medium scales. On all-time scales, sunshine duration was the best single variable for explaining PM2.5 variations and precipitation was the best single variable explaining O3 variations. When compared to single meteorological factors, the combination of multiple meteorological factors significantly improved the ability to explain variations in PM2.5 and O3 on small-time scales. (3) Atmospheric teleconnection factors were important driving factors affecting the response relationships of PM2.5 and O3 on meteorological factors and they had greater impact on the relationship at medium-time scales compared to small- and large-time scales.

Reversible modulation of protocell volume via collective response of functional protein in its membrane.

Volume change plays an important role in biological cells to regulate their internal microenvironment. To adapt to the rapid variation of the surface area during the volume change, the lipid membrane is dynamically modulated via membrane folding invagination, or spontaneous uptake or release of lipid molecules under osmotic pressure. Here, we demonstrate an alternative approach to design a functional protocellular system capable of dynamically adjusting its volume and intracellular microenvironment in response to the alteration of pH. By assembling and subsequently cross-linking pH-responsive caseinate at the water-oil interface, the caseinate-based protocell with more than ten thousand caseinate units in its membrane was established and showed a reversible volume and pore size change to pH variation due to the collective response of the caseinate in the membrane, which could be used to control the spatial distribution of proto-organelle by regulating of the viscosity inside the protocell.